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Clinical Trial Results:
Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors

Summary
EudraCT number	2019-001946-17
Trial protocol	GB IT
Global end of trial date	28 Nov 2023

Results information
Results version number	v1(current)
This version publication date	07 Dec 2024
First version publication date	07 Dec 2024
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

C5741002

ISRCTN number

US NCT number

NCT04032704

WHO universal trial number (UTN)

Other trial identifiers

Seagen: SGNLVA-005

Sponsor organisation name

Seagen Inc.

Sponsor organisation address

21823 30th Drive S.E., Bothell, United States, 98021

Public contact

Chief Medical Officer, Seagen Inc., 1 8554732436, medinfo@seagen.com

Scientific contact

Chief Medical Officer, Seagen Inc., 1 8554732436, medinfo@seagen.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

17 Jan 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Nov 2023

Was the trial ended prematurely?

Main objective of the trial

To evaluate antitumor activity of LV as monotherapy (Part A, Part B, and Part C Arm 1 [Cohort 8 only]) and in combination with pembrolizumab (Part C Arm 2 and Arm 3, Cohort 8 only)

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials participants were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

09 Oct 2019

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy, Safety

Long term follow-up duration

38 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 28

Country: Number of subjects enrolled

Italy: 34

Country: Number of subjects enrolled

Korea, Republic of: 28

Country: Number of subjects enrolled

Taiwan: 9

Country: Number of subjects enrolled

United Kingdom: 22

Country: Number of subjects enrolled

United States: 84

Worldwide total number of subjects

205

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)

108

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study had Parts A, B and C. Study was terminated and Part C was not opened. A total of 205 participants were enrolled in Part A (49 participants) and Part B (156 participants) of this study. In Part A all enrolled participants received study intervention while in Part B, 2 participants did not receive study intervention.

Screening details

Cohort (C): C1:small cell lung cancer (SCLC) [A, B]; C2:non-SCLC-squamous (sq)[NSCLC-sq] {A, B}; C3:NSCLC-nonsq (A, B); C4:head & neck sq cell carcinoma (SCC)[HNSCC] {A, B}; C5: esophageal SSC (esophageal-sq)[A, B]; C6:gastric & gastroesophageal junction(GEJ) adenocarcinoma (A, B); C7:castration-resistant prostate cancer(CRPC) (B);C8:melanoma (B).

Period 1 title

Baseline Period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part A: Cohort 1, LV 2.5 mg/kg

Arm description

Participants with SCLC were administered ladiratuzumab vedotin (LV) 2.5 milligram per kilogram (mg/kg) as intravenous (IV) infusion on Day 1 of each 21-day cycle (q3wk).

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 2.5 mg/kg as an IV infusion on Day 1 q3wk.

Part A: Cohort 2, LV 2.5 mg/kg

Arm description

Participants with NSCLC-squamous were administered LV 2.5 mg/kg as IV infusion q3wk.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 2.5 mg/kg as an IV infusion on Day 1 q3wk.

Part A: Cohort 3, LV 2.5 mg/kg

Arm description

Participants with NSCLC-nonsquamous were administered LV 2.5 mg/kg as IV infusion q3wk.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 2.5 mg/kg as an IV infusion on Day 1 q3wk.

Part A: Cohort 4, LV 2.5 mg/kg

Arm description

Participants with HNSCC were administered LV 2.5 mg/kg as IV infusion q3wk.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 2.5 mg/kg as an IV infusion on Day 1 q3wk.

Part A: Cohort 5, LV 2.5 mg/kg

Arm description

Participants with esophageal-squamous were administered LV 2.5 mg/kg as IV infusion q3wk.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 2.5 mg/kg as an IV infusion on Day 1 q3wk.

Part A: Cohort 6, LV 2.5 mg/kg

Arm description

Participants with GEJ were administered LV 2.5 mg/kg as IV infusion q3wk.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 2.5 mg/kg as an IV infusion on Day 1 q3wk.

Part B: Cohort 1, LV 1.25 mg/kg

Arm description

Participants with SCLC were administered LV 1.25 mg/kg on Days 1, 8 and 15 of each 21-day cycle (q1wk) as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.25 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 2, LV 1.25 mg/kg

Arm description

Participants with NSCLC-squamous were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.25 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 3, LV 1.25 mg/kg

Arm description

Participants with NSCLC-nonsquamous were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.25 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 4, LV 1.25 mg/kg

Arm description

Participants with HNSCC were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.25 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 5, LV 1.25 mg/kg

Arm description

Participants with esophageal-squamous were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.25 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 6, LV 1.25 mg/kg

Arm description

Participants with GEJ were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.25 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 7, LV 1.25 mg/kg

Arm description

Participants with CRPC were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.25 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 8, LV 1.25 mg/kg

Arm description

Participants with melanoma were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.25 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 1, LV 1.0 mg/kg

Arm description

Participants with SCLC were administered LV 1.0 mg/kg q1wk on Days 1, 8 and 15 as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.0 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 3, LV 1.0 mg/kg

Arm description

Participants with NSCLC-nonsquamous were administered LV 1.0 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.0 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 4, LV 1.0 mg/kg

Arm description

Participants with HNSCC were administered LV 1.0 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.0 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Part B: Cohort 6, LV 1.0 mg/kg

Arm description

Participants with GEJ were administered LV 1.0 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Arm type

Experimental

Investigational medicinal product name

Ladiratuzumab vedotin (LV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received LV 1.0 mg/kg as an IV infusion on Day 1, 8 and 15 q3wk.

Number of subjects in period 1	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg	Part B: Cohort 1, LV 1.25 mg/kg	Part B: Cohort 2, LV 1.25 mg/kg	Part B: Cohort 3, LV 1.25 mg/kg	Part B: Cohort 4, LV 1.25 mg/kg	Part B: Cohort 5, LV 1.25 mg/kg	Part B: Cohort 6, LV 1.25 mg/kg	Part B: Cohort 7, LV 1.25 mg/kg	Part B: Cohort 8, LV 1.25 mg/kg	Part B: Cohort 1, LV 1.0 mg/kg	Part B: Cohort 3, LV 1.0 mg/kg	Part B: Cohort 4, LV 1.0 mg/kg	Part B: Cohort 6, LV 1.0 mg/kg
Started	10	2	13	7	5	12	16	16	19	14	17	21	14	31	2	2	2	2
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	10	2	13	7	5	12	16	16	19	14	17	21	14	31	2	2	2	2
Adverse event, serious fatal	9	2	10	7	4	5	13	13	14	12	12	13	7	17	2	1	2	2
Study termination by Sponsor	-	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-
Consent withdrawn by subject	-	-	3	-	1	7	3	2	2	1	4	6	2	1	-	1	-	-
Unspecified	-	-	-	-	-	-	-	1	2	1	1	1	5	13	-	-	-	-
Lost to follow-up	1	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-	-

Baseline characteristics

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Reporting group title

Part A: Cohort 1, LV 2.5 mg/kg

Reporting group description

Participants with SCLC were administered ladiratuzumab vedotin (LV) 2.5 milligram per kilogram (mg/kg) as intravenous (IV) infusion on Day 1 of each 21-day cycle (q3wk).

Reporting group title

Part A: Cohort 2, LV 2.5 mg/kg

Reporting group description

Participants with NSCLC-squamous were administered LV 2.5 mg/kg as IV infusion q3wk.

Reporting group title

Part A: Cohort 3, LV 2.5 mg/kg

Reporting group description

Participants with NSCLC-nonsquamous were administered LV 2.5 mg/kg as IV infusion q3wk.

Reporting group title

Part A: Cohort 4, LV 2.5 mg/kg

Reporting group description

Participants with HNSCC were administered LV 2.5 mg/kg as IV infusion q3wk.

Reporting group title

Part A: Cohort 5, LV 2.5 mg/kg

Reporting group description

Participants with esophageal-squamous were administered LV 2.5 mg/kg as IV infusion q3wk.

Reporting group title

Part A: Cohort 6, LV 2.5 mg/kg

Reporting group description

Participants with GEJ were administered LV 2.5 mg/kg as IV infusion q3wk.

Reporting group title

Part B: Cohort 1, LV 1.25 mg/kg

Reporting group description

Participants with SCLC were administered LV 1.25 mg/kg on Days 1, 8 and 15 of each 21-day cycle (q1wk) as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 2, LV 1.25 mg/kg

Reporting group description

Participants with NSCLC-squamous were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 3, LV 1.25 mg/kg

Reporting group description

Participants with NSCLC-nonsquamous were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 4, LV 1.25 mg/kg

Reporting group description

Participants with HNSCC were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 5, LV 1.25 mg/kg

Reporting group description

Participants with esophageal-squamous were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 6, LV 1.25 mg/kg

Reporting group description

Participants with GEJ were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 7, LV 1.25 mg/kg

Reporting group description

Participants with CRPC were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 8, LV 1.25 mg/kg

Reporting group description

Participants with melanoma were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 1, LV 1.0 mg/kg

Reporting group description

Participants with SCLC were administered LV 1.0 mg/kg q1wk on Days 1, 8 and 15 as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 3, LV 1.0 mg/kg

Reporting group description

Participants with NSCLC-nonsquamous were administered LV 1.0 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 4, LV 1.0 mg/kg

Reporting group description

Participants with HNSCC were administered LV 1.0 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 6, LV 1.0 mg/kg

Reporting group description

Participants with GEJ were administered LV 1.0 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg	Part B: Cohort 1, LV 1.25 mg/kg	Part B: Cohort 2, LV 1.25 mg/kg	Part B: Cohort 3, LV 1.25 mg/kg	Part B: Cohort 4, LV 1.25 mg/kg	Part B: Cohort 5, LV 1.25 mg/kg	Part B: Cohort 6, LV 1.25 mg/kg	Part B: Cohort 7, LV 1.25 mg/kg	Part B: Cohort 8, LV 1.25 mg/kg	Part B: Cohort 1, LV 1.0 mg/kg	Part B: Cohort 3, LV 1.0 mg/kg	Part B: Cohort 4, LV 1.0 mg/kg	Part B: Cohort 6, LV 1.0 mg/kg	Total
Number of subjects	10	2	13	7	5	12	16	16	19	14	17	21	14	31	2	2	2	2	205
Age categorical
Units: Participants
Adults (18-64 years)	5	0	6	4	2	7	9	6	10	8	13	14	4	15	2	1	2	0	108
From 65-84 years	5	2	6	3	2	5	6	10	9	6	4	7	9	16	0	1	0	2	93
85 years and over	0	0	1	0	1	0	1	0	0	0	0	0	1	0	0	0	0	0	4
Age Continuous
Units: Years
arithmetic mean (standard deviation)	63.7 ( 9.5 )	80.5 ( 4.9 )	67.2 ( 13.7 )	63.1 ( 12.3 )	70.8 ( 11.2 )	64.7 ( 10.3 )	65.0 ( 10.7 )	67.3 ( 8.8 )	63.9 ( 9.3 )	63.8 ( 9.9 )	60.5 ( 8.3 )	60.9 ( 8.9 )	71.6 ( 8.3 )	62.9 ( 12.2 )	61.0 ( 1.4 )	66.0 ( 2.8 )	56.0 ( 2.8 )	77.5 ( 6.4 )	-
Sex: Female, Male
Units: Participants
Female	2	1	8	2	1	0	7	4	5	3	2	3	0	8	0	1	0	0	47
Male	8	1	5	5	4	12	9	12	14	11	15	18	14	23	2	1	2	2	158
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian	3	0	2	1	4	8	2	1	3	1	9	4	0	3	0	0	0	0	41
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	1	0	1	0	0	0	0	0	1	1	0	0	1	0	0	0	0	0	5
White	5	2	10	6	1	4	14	13	14	11	5	12	10	26	2	2	2	2	141
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	1	0	0	0	0	0	0	2	1	1	3	5	3	2	0	0	0	0	18
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	1	0	0	3
Not Hispanic or Latino	10	2	13	7	5	12	15	13	18	14	14	16	12	28	2	1	2	2	186
Unknown or Not Reported	0	0	0	0	0	0	1	2	1	0	3	4	2	3	0	0	0	0	16

End points

Top of page

Reporting group title

Part A: Cohort 1, LV 2.5 mg/kg

Reporting group description

Participants with SCLC were administered ladiratuzumab vedotin (LV) 2.5 milligram per kilogram (mg/kg) as intravenous (IV) infusion on Day 1 of each 21-day cycle (q3wk).

Reporting group title

Part A: Cohort 2, LV 2.5 mg/kg

Reporting group description

Participants with NSCLC-squamous were administered LV 2.5 mg/kg as IV infusion q3wk.

Reporting group title

Part A: Cohort 3, LV 2.5 mg/kg

Reporting group description

Participants with NSCLC-nonsquamous were administered LV 2.5 mg/kg as IV infusion q3wk.

Reporting group title

Part A: Cohort 4, LV 2.5 mg/kg

Reporting group description

Participants with HNSCC were administered LV 2.5 mg/kg as IV infusion q3wk.

Reporting group title

Part A: Cohort 5, LV 2.5 mg/kg

Reporting group description

Participants with esophageal-squamous were administered LV 2.5 mg/kg as IV infusion q3wk.

Reporting group title

Part A: Cohort 6, LV 2.5 mg/kg

Reporting group description

Participants with GEJ were administered LV 2.5 mg/kg as IV infusion q3wk.

Reporting group title

Part B: Cohort 1, LV 1.25 mg/kg

Reporting group description

Participants with SCLC were administered LV 1.25 mg/kg on Days 1, 8 and 15 of each 21-day cycle (q1wk) as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 2, LV 1.25 mg/kg

Reporting group description

Participants with NSCLC-squamous were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 3, LV 1.25 mg/kg

Reporting group description

Participants with NSCLC-nonsquamous were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 4, LV 1.25 mg/kg

Reporting group description

Participants with HNSCC were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 5, LV 1.25 mg/kg

Reporting group description

Participants with esophageal-squamous were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 6, LV 1.25 mg/kg

Reporting group description

Participants with GEJ were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 7, LV 1.25 mg/kg

Reporting group description

Participants with CRPC were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 8, LV 1.25 mg/kg

Reporting group description

Participants with melanoma were administered LV 1.25 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 1, LV 1.0 mg/kg

Reporting group description

Participants with SCLC were administered LV 1.0 mg/kg q1wk on Days 1, 8 and 15 as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 3, LV 1.0 mg/kg

Reporting group description

Participants with NSCLC-nonsquamous were administered LV 1.0 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 4, LV 1.0 mg/kg

Reporting group description

Participants with HNSCC were administered LV 1.0 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Reporting group title

Part B: Cohort 6, LV 1.0 mg/kg

Reporting group description

Participants with GEJ were administered LV 1.0 mg/kg on Days 1, 8 and 15 q1wk as a 30-minute IV infusion.

Primary: Part A: Confirmed Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

Top of page

End point title

Part A: Confirmed Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) ^[1] ^[2]

End point description

Confirmed ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (mm). PR was defined as more than or equal to (>=) 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not have at least 2 post-baseline response assessment (initial response and confirmation scan) were counted as non-responders. The full analysis set (FAS) included all participants who received any amount of study drug.

End point type

Primary

End point timeframe

From the first dose of study treatment until the first documented CR or PR or new anticancer therapies or death, whichever occurred first (maximum up to 8.3 months)

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

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	10	2	13	7	5	12
Units: Percentage of participants
number (confidence interval 95%)	10 (0.3 to 44.5)	0 (0.0 to 84.2)	8 (0.2 to 36.0)	14 (0.4 to 57.9)	20 (0.5 to 71.6)	8 (0.2 to 38.5)

No statistical analyses for this end point

Primary: Part B: Confirmed ORR as Determined by Investigator According to RECIST v1.1

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End point title

Part B: Confirmed ORR as Determined by Investigator According to RECIST v1.1 ^[3] ^[4]

End point description

Confirmed ORR was defined as the percentage of participants with a confirmed CR or PR per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR was defined as >= 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not have at least 2 post-baseline response assessment (initial response and confirmation scan) were counted as non-responders. The FAS included all participants who received any amount of study drug. Here, 'Number of Participants Analysed' signifies participants evaluable for this endpoint.

End point type

Primary

End point timeframe

From the first dose of study treatment until the first documented CR or PR or new anticancer therapies or death, whichever occurred first (maximum up to 34.7 months for 1.25 mg/kg and 5.7 months for 1 mg/kg dose level)

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: This endpoint was planned to be analysed only for the specified reporting arms.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

Part B: Cohort 1, LV 1.25 mg/kg

Part B: Cohort 2, LV 1.25 mg/kg

Part B: Cohort 3, LV 1.25 mg/kg

Part B: Cohort 4, LV 1.25 mg/kg

Part B: Cohort 5, LV 1.25 mg/kg

Part B: Cohort 6, LV 1.25 mg/kg

Part B: Cohort 7, LV 1.25 mg/kg

Part B: Cohort 8, LV 1.25 mg/kg

Part B: Cohort 1, LV 1.0 mg/kg

Part B: Cohort 3, LV 1.0 mg/kg

Part B: Cohort 4, LV 1.0 mg/kg

Part B: Cohort 6, LV 1.0 mg/kg

Number of subjects analysed

Units: Percentage of participants

number (confidence interval 95%)

6 (0.2 to 30.2)

13 (1.6 to 38.3)

11 (1.3 to 33.1)

0 (0.0 to 23.2)

18 (3.8 to 43.4)

14 (3.0 to 36.3)

0 (0.0 to 24.7)

20 (7.7 to 38.6)

0 (0.0 to 84.2)

50 (1.3 to 98.7)

No statistical analyses for this end point

Primary: Part B: Confirmed Prostate-Specific Antigen (PSA) Response Rate as Determined by Investigator According to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria, for Prostate Cancer

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End point title

Part B: Confirmed Prostate-Specific Antigen (PSA) Response Rate as Determined by Investigator According to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria, for Prostate Cancer ^[5] ^[6]

End point description

Confirmed PSA response rate was defined as percentage of participants with reduction from baseline PSA level of at least 50%, measured twice >= 3 weeks apart. PSA progression was defined as per PCWG3 criteria- a) if a participant presented first a decline from baseline, progression was defined as the first PSA increase that was >=25% and >=2 nanograms per milliliter (ng/mL) above the nadir, and which was confirmed by a consecutive second value >=3 weeks later that fulfilled the same criteria (that is, a confirmed rising trend); b) if a participant did not present a decline from baseline, progression was defined as the first PSA increase that was >=25% and >=2 ng/mL increased from baseline beyond 12 weeks. The FAS included all participants who received any amount of study drug. As prespecified in protocol, this endpoint was planned to be analysed only in Part B: Cohort 7, LV 1.25 mg/kg arm. Here, 'Number of Participants Analysed' signifies participants evaluable for this endpoint.

End point type

Primary

End point timeframe

From the first dose of study treatment up to the date of last response assessment (maximum up to 13.5 months)

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

End point values	Part B: Cohort 7, LV 1.25 mg/kg
Number of subjects analysed	13
Units: Percentage of participants
number (confidence interval 95%)	23 (5.0 to 53.8)

No statistical analyses for this end point

Secondary: Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Related TEAEs and >= Grade 3 TEAE

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End point title

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Related TEAEs and >= Grade 3 TEAE ^[7]

End point description

Adverse event (AE) was any untoward medical occurrence in a participant/ clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. AEs included both SAEs ad all non-SAEs. TEAEs were defined as newly occurring (not present at baseline)/worsening after first dose of study treatment. TESAEs were any untoward medical occurrence at any dose that: suspected to cause death; life-threatening; required hospitalization; persistent/significant disability/incapacity & may cause congenital anomaly/birth defect. Treatment related TEAEs were related to study treatment and relatedness was judged by investigator. TEAEs were graded according to National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 4.03 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Safety analysis set included all participants who received any amount of study drug.

End point type

Secondary

End point timeframe

From start of study treatment up to 30 days after last dose of study treatment (maximum up to 37.5 months)

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	10	2	13	7	5	12
Units: Participants
TEAEs	10	2	13	7	5	12
TESAEs	5	1	7	2	3	3
Treatment Related TEAEs	9	2	11	7	5	11
TEAEs (>= Grade 3)	7	1	9	4	4	6

No statistical analyses for this end point

Secondary: Part B: Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >= Grade 3 TEAE

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End point title

Part B: Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >= Grade 3 TEAE ^[8]

End point description

AE was any untoward medical occurrence in participant, or clinical investigational participant administered medicinal product, and which does not necessarily have causal relationship with this treatment. AEs included both SAEs and all non-SAEs. TEAEs were defined as newly occurring (not present at baseline) or worsening after first dose of study treatment. TESAEs were any untoward medical occurrence at any dose that: suspected to cause death; life-threatening; required hospitalisation; persistent or significant disability or incapacity and may cause congenital anomaly or birth defect. Treatment related TEAEs were related to study treatment and relatedness was judged by investigator. TEAEs were graded according to NCI-CTCAE v4.03 (grade 1= mild, grade 2= moderate, grade 3= severe and grade 4= life-threatening). Safety analysis set included all participants who received any amount of study drug.

End point type

Secondary

End point timeframe

From start of study treatment up to 30 days after last dose of study treatment (maximum up to 37.5 months)

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part B: Cohort 1, LV 1.25 mg/kg	Part B: Cohort 2, LV 1.25 mg/kg	Part B: Cohort 3, LV 1.25 mg/kg	Part B: Cohort 4, LV 1.25 mg/kg	Part B: Cohort 5, LV 1.25 mg/kg	Part B: Cohort 6, LV 1.25 mg/kg	Part B: Cohort 7, LV 1.25 mg/kg	Part B: Cohort 8, LV 1.25 mg/kg	Part B: Cohort 1, LV 1.0 mg/kg	Part B: Cohort 3, LV 1.0 mg/kg	Part B: Cohort 4, LV 1.0 mg/kg	Part B: Cohort 6, LV 1.0 mg/kg
Number of subjects analysed	16	16	19	14	17	21	13	30	2	2	2	2
Units: Participants
TEAEs	15	16	19	14	17	21	13	30	2	2	2	2
TESAEs	6	5	9	8	9	12	4	11	1	2	1	0
Treatment Related TEAEs	13	16	18	12	17	19	12	28	2	2	2	2
TEAEs (>= Grade 3)	12	11	14	11	13	17	8	17	1	2	1	0

No statistical analyses for this end point

Secondary: Part A: Confirmed Investigator Determined Disease Control Rate (DCR) According to RECIST v1.1

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End point title

Part A: Confirmed Investigator Determined Disease Control Rate (DCR) According to RECIST v1.1 ^[9]

End point description

DCR: percentage of participants who achieved confirmed and unconfirmed CR/PR per RECIST v1.1 or met stable disease (SD) criteria at least once after start of study treatment at minimum interval of 5 weeks. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: >= 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference smallest sum diameters while on study. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included baseline sum if that is smallest). In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 0.5cm. Appearance of one or more new lesions was also considered progression. FAS: all participants who received any amount of study drug.

End point type

Secondary

End point timeframe

From the first dose of study treatment until the first documented CR, PR or SD or new anticancer therapies or death, whichever occurred first (maximum up to 4.1 months)

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	10	2	13	7	5	12
Units: Percentage of participants
number (confidence interval 95%)	40 (12.2 to 73.8)	50 (1.3 to 98.7)	46 (19.2 to 74.9)	57 (18.4 to 90.1)	60 (14.7 to 94.7)	33 (9.9 to 65.1)

No statistical analyses for this end point

Secondary: Part B: Confirmed Investigator Determined DCR According to RECIST v1.1

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End point title

Part B: Confirmed Investigator Determined DCR According to RECIST v1.1 ^[10]

End point description

DCR: percentage of participants who achieved confirmed and unconfirmed CR/PR per RECIST v1.1 or met SD criteria at least once after start of study treatment at minimum interval of 5 weeks. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10mm. PR: >= 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included baseline sum if that is smallest). In addition to relative increase of 20%, sum must also demonstrate absolute increase of at least 0.5 centimeter (cm). Appearance of one or more new lesions was also considered progression. FAS: all participants who received any amount of study drug. 'N'= participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

From the first dose of study treatment until the first documented CR, PR or SD or new anticancer therapies or death, whichever occurred first (maximum up to 5.5 months for 1.25 mg/kg and 1.5 months for 1 mg/kg dose level)

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

Part B: Cohort 1, LV 1.25 mg/kg

Part B: Cohort 2, LV 1.25 mg/kg

Part B: Cohort 3, LV 1.25 mg/kg

Part B: Cohort 4, LV 1.25 mg/kg

Part B: Cohort 5, LV 1.25 mg/kg

Part B: Cohort 6, LV 1.25 mg/kg

Part B: Cohort 7, LV 1.25 mg/kg

Part B: Cohort 8, LV 1.25 mg/kg

Part B: Cohort 1, LV 1.0 mg/kg

Part B: Cohort 3, LV 1.0 mg/kg

Part B: Cohort 4, LV 1.0 mg/kg

Part B: Cohort 6, LV 1.0 mg/kg

Number of subjects analysed

Units: Percentage of participants

number (confidence interval 95%)

19 (4.0 to 45.6)

50 (24.7 to 75.3)

58 (33.5 to 79.7)

64 (35.1 to 87.2)

59 (32.9 to 81.6)

52 (29.8 to 74.3)

62 (31.6 to 86.1)

77 (57.7 to 90.1)

50 (1.3 to 98.7)

0 (0.0 to 84.2)

100 (15.8 to 100.0)

No statistical analyses for this end point

Secondary: Part A: Confirmed Investigator Determined Duration of Response (DOR) According to RECIST v1.1

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End point title

Part A: Confirmed Investigator Determined Duration of Response (DOR) According to RECIST v1.1 ^[11]

End point description

DOR: time from 1st documentation of OR to 1st documentation of PD/death due to any cause, whichever occurred first. CR: disappearance of target lesions (TL). Pathological lymph nodes must have reduction in short axis to <10mm. PR: >= 30% decrease in sum of diameters of TL. Participants don’t have PD, are on study at time of analysis/removed from study prior to documentation of PD = censored at last disease assessment (DA) documenting absence of PD. Participants who started new anticancer treatment prior to documentation of PD = censored at last DA prior to start of new treatment. PD: at least 20% increase in sum of diameters of TL. Sum must demonstrate increase of 0.5 cm. Appearance of 1/more new lesions = progression. Kaplan-Meier method was used. FAS analysed. 'N'=participants evaluable for endpoint. 99999 = 1 participant evaluable, lower & upper limit (UL) of 95% CI could not be estimated. 88888 = no participant had event of interest; results could not be estimated.

End point type

Secondary

End point timeframe

From the first documentation of CR or PR to PD or death or censoring whichever occurred first (maximum up to 5.7 months)

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	1	0 ^[12]	1	1	1	1
Units: Months
median (confidence interval 95%)	5.7 (-99999 to 99999)	( to )	5.5 (-99999 to 99999)	3.7 (-99999 to 99999)	2.7 (-99999 to 99999)	88888 (-88888 to 88888)

Notes
[12] - No participant had CR or PR in this arm.

No statistical analyses for this end point

Secondary: Part B: Confirmed Investigator Determined DOR According to RECIST v1.1

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End point title

Part B: Confirmed Investigator Determined DOR According to RECIST v1.1 ^[13]

End point description

DOR: time from 1st documentation (doc) of OR to 1st doc of PD/death due to any cause, whichever occurred 1st.CR: disappearance of TL. Pathological lymph nodes must have reduction in short axis to <10mm.PR: >=30% decrease in sum of diameters of TL. Participants don’t have PD, are on study at time of analysis/removed from study prior to doc of PD wascensored at last disease assessment (DA)documenting absence of PD. Participants who started new anticancer treatment prior to doc of PD=censored at last DA prior to start of new treatment. PD:at least 20% increase(inc)in sum of diameters of TL. Sum must demonstrate inc of 0.5cm. Appearance of 1/more new lesions=progression. Kaplan-Meier method was used. FAS analysed.'N'=participants evaluable for endpoint.99999=1 participant evaluable, lower & UL of 95% CI could not be estimated. 88888= no participant had event of interest; results could not be estimated. 77777= insufficient number of participants with events to calculate UL of 95%CI.

End point type

Secondary

End point timeframe

From the first documentation of CR or PR to PD or death or censoring whichever occurred first (maximum up to 32.0 months for 1.25 mg/kg and 4.2 months for 1 mg/kg dose level)

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

Part B: Cohort 1, LV 1.25 mg/kg

Part B: Cohort 2, LV 1.25 mg/kg

Part B: Cohort 3, LV 1.25 mg/kg

Part B: Cohort 4, LV 1.25 mg/kg

Part B: Cohort 5, LV 1.25 mg/kg

Part B: Cohort 6, LV 1.25 mg/kg

Part B: Cohort 7, LV 1.25 mg/kg

Part B: Cohort 8, LV 1.25 mg/kg

Part B: Cohort 1, LV 1.0 mg/kg

Part B: Cohort 3, LV 1.0 mg/kg

Part B: Cohort 4, LV 1.0 mg/kg

Part B: Cohort 6, LV 1.0 mg/kg

Number of subjects analysed

0 ^[14]

0 ^[15]

0 ^[16]

0 ^[17]

0 ^[18]

Units: Months

median (confidence interval 95%)

88888 (-88888 to 88888)

7.5 (5.78 to 77777)

77777 (16.59 to 77777)

( to )

77777 (3.06 to 77777)

3.9 (2.60 to 77777)

( to )

8.3 (5.62 to 77777)

( to )

4.2 (-99999 to 99999)

Notes
[14] - No participant had CR or PR in this arm.
[15] - No participant had CR or PR in this arm.
[16] - No participant had CR or PR in this arm.
[17] - No participant had CR or PR in this arm.
[18] - No participant had CR or PR in this arm.

No statistical analyses for this end point

Secondary: Part B: Confirmed Investigator Determined PSA-DOR, for Prostate Cancer

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End point title

Part B: Confirmed Investigator Determined PSA-DOR, for Prostate Cancer ^[19]

End point description

PSA-DOR=time from 1st documentation of PSA response(confirmed 3 weeks apart)to 1st documentation of PSA progression/death due to any cause,whichever occurred first.Confirmed PSA response rate=percentage of participants with reduction from baseline PSA of 50%,measured twice >=3 weeks apart.Participants who don’t have PD,are still on study at time of analysis/removed from study prior to documentation of PD was censored at date of last disease assessment documenting absence of PD.Participants who started new anticancer treatment prior to documentation of PD were censored at date of last disease assessment prior to start of new treatment.Confidence interval (CI) calculated by complementary log-log transformation method.FAS=participants who received any amount of drug.As prespecified in protocol,endpoint was planned to be analysed only in Part B:Cohort 7,LV 1.25mg/kg arm.'N'=participants evaluable for endpoint.77777=insufficient participants with events to calculate upper limit of 95% CI.

End point type

Secondary

End point timeframe

From the first documentation of CR or PR to PD or death or censoring whichever occurred first (maximum up to 3 months)

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part B: Cohort 7, LV 1.25 mg/kg
Number of subjects analysed	3
Units: Months
median (confidence interval 95%)	3.0 (1.9 to 77777)

No statistical analyses for this end point

Secondary: Part A: Confirmed Investigator Determined Progression Free Survival (PFS) According to RECIST v1.1

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End point title

Part A: Confirmed Investigator Determined Progression Free Survival (PFS) According to RECIST v1.1 ^[20]

End point description

PFS:time from start of study treatment to 1st documentation of PD by RECIST v1.1. Participants who do not have PD, are still on study at time of analysis/removed from study prior to documentation of PD were censored at date of last disease assessment documenting absence of PD. Participants who started new anticancer treatment prior to documentation of PD were censored at date of last disease assessment prior to start of new treatment. PD:at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included baseline sum if that is smallest on study). Sum must also demonstrate absolute increase of at least 0.5cm. Appearance of 1 or more new lesions was considered progression. Median was estimated using Kaplan-Meier method; CI was calculated using complementary log-log transformation method. FAS=all participants who received any amount of study drug. 77777=insufficient number of participants with events to calculate upper limit of 95% CI.

End point type

Secondary

End point timeframe

From first dose of study treatment to the date of PD or clinical PD or censoring whichever occurred first (maximum up to 8.3 months)

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	10	2	13	7	5	12
Units: Months
median (confidence interval 95%)	1.4 (0.53 to 2.69)	1.5 (1.25 to 77777)	2.5 (0.46 to 4.17)	2.3 (0.33 to 4.86)	2.9 (0.59 to 77777)	1.4 (1.31 to 4.17)

No statistical analyses for this end point

Secondary: Part B: Confirmed Investigator Determined PFS According to RECIST v1.1

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End point title

Part B: Confirmed Investigator Determined PFS According to RECIST v1.1 ^[21]

End point description

PFS: time from start of treatment to 1st documentation of PD by RECIST v1.1. Participants who do not have PD, are still on study at time of analysis/removed from study prior to documentation of PD were censored at date of last disease assessment documenting absence of PD. Participants who started new anticancer treatment prior to documentation of PD were censored at date of last disease assessment prior to start of new treatment. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. Sum must also demonstrate absolute increase of at least 0.5 cm. Appearance of one or more new lesions was also considered progression. Median was estimated using Kaplan-Meier method and CI was calculated using complementary log-log transformation method. FAS: all participants who received any amount of study drug. 'N'= participants evaluable for endpoint. 77777= insufficient number of participants with events to calculate upper limit of 95% CI.

End point type

Secondary

End point timeframe

From first dose of study treatment to the date of PD or clinical PD or censoring whichever occurred first (maximum up to 34.7 months for 1.25 mg/kg and 5.7 months for 1 mg/kg dose level)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

Part B: Cohort 1, LV 1.25 mg/kg

Part B: Cohort 2, LV 1.25 mg/kg

Part B: Cohort 3, LV 1.25 mg/kg

Part B: Cohort 4, LV 1.25 mg/kg

Part B: Cohort 5, LV 1.25 mg/kg

Part B: Cohort 6, LV 1.25 mg/kg

Part B: Cohort 7, LV 1.25 mg/kg

Part B: Cohort 8, LV 1.25 mg/kg

Part B: Cohort 1, LV 1.0 mg/kg

Part B: Cohort 3, LV 1.0 mg/kg

Part B: Cohort 4, LV 1.0 mg/kg

Part B: Cohort 6, LV 1.0 mg/kg

Number of subjects analysed

Units: Months

median (confidence interval 95%)

1.4 (1.18 to 2.04)

1.8 (1.12 to 5.72)

2.4 (1.31 to 2.96)

2.7 (1.18 to 2.86)

2.8 (1.38 to 3.32)

2.3 (1.25 to 2.73)

4.9 (2.10 to 5.65)

4.2 (2.50 to 6.97)

1.9 (1.02 to 77777)

1.3 (-77777 to 77777)

1.5 (1.35 to 77777)

4.2 (2.76 to 77777)

No statistical analyses for this end point

Secondary: Part B: Confirmed Investigator Determined PSA-PFS, for Prostate Cancer

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End point title

Part B: Confirmed Investigator Determined PSA-PFS, for Prostate Cancer ^[22]

End point description

PSA-PFS: time from start of treatment to 1st documentation of PSA progression/death due to any cause,whichever occurred 1st.Participants who don’t have PD,are still on study at time of analysis/removed from study prior to documentation of PD was censored at date of last disease assessment documenting absence of PD. Participants who started new anticancer treatment prior to documentation of PD were censored at date of last disease assessment prior to start of new treatment.PD: at least 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study.Sum must also demonstrate absolute increase of 0.5cm.Appearance of 1 or more new lesions was considered progression. Median was estimated using Kaplan-Meier;CI was calculated using complementary log-log transformation. FAS:participants who received any amount of study drug.As prespecified in protocol,endpoint planned to be analysed only in Part B:Cohort 7,LV 1.25mg/kg arm.'N'=participants evaluable for endpoint.

End point type

Secondary

End point timeframe

From first dose of study treatment to the date of PD or clinical PD or censoring whichever occurred first (maximum up to 5.7 months)

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part B: Cohort 7, LV 1.25 mg/kg
Number of subjects analysed	9
Units: Months
median (confidence interval 95%)	3.7 (2.8 to 5.1)

No statistical analyses for this end point

Secondary: Part A: Overall Survival (OS)

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End point title

Part A: Overall Survival (OS) ^[23]

End point description

OS was defined as the time from the start of study treatment to date of death due to any cause. Participants who do not have PD and are still on study at the time of an analysis or who are removed from the study prior to documentation of PD was censored at the date of last disease assessment documenting absence of PD. Participants who started a new anticancer treatment prior to documentation of PD were censored at the date of last disease assessment prior to the start of new treatment. Median was estimated using the Kaplan-Meier method. The FAS included all participants who received any amount of study drug. 77777= insufficient number of participants with events to calculate the upper limit of the 95% confidence interval.

End point type

Secondary

End point timeframe

From first dose of study treatment to the date of death or censoring whichever occurred first (maximum up to 27.5 months)

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	10	2	13	7	5	12
Units: Months
median (confidence interval 95%)	6.1 (1.38 to 15.84)	2.5 (1.74 to 77777)	6.5 (2.20 to 16.95)	4.8 (0.33 to 6.97)	7.2 (0.59 to 77777)	8.7 (3.98 to 77777)

No statistical analyses for this end point

Secondary: Part B: Overall Survival

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End point title

Part B: Overall Survival ^[24]

End point description

End point type

Secondary

End point timeframe

From first dose of study treatment to the date of death or censoring whichever occurred first (maximum up to 37.5 months for 1.25 mg/kg and 20.9 months for 1 mg/kg dose level)

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

Part B: Cohort 1, LV 1.25 mg/kg

Part B: Cohort 2, LV 1.25 mg/kg

Part B: Cohort 3, LV 1.25 mg/kg

Part B: Cohort 4, LV 1.25 mg/kg

Part B: Cohort 5, LV 1.25 mg/kg

Part B: Cohort 6, LV 1.25 mg/kg

Part B: Cohort 7, LV 1.25 mg/kg

Part B: Cohort 8, LV 1.25 mg/kg

Part B: Cohort 1, LV 1.0 mg/kg

Part B: Cohort 3, LV 1.0 mg/kg

Part B: Cohort 4, LV 1.0 mg/kg

Part B: Cohort 6, LV 1.0 mg/kg

Number of subjects analysed

Units: Months

median (confidence interval 95%)

4.7 (3.45 to 8.74)

9.0 (4.53 to 12.68)

9.3 (2.92 to 20.14)

5.2 (3.42 to 18.33)

12.7 (4.17 to 15.28)

3.8 (1.77 to 8.61)

10.1 (6.47 to 77777)

11.5 (9.26 to 15.41)

11.1 (1.22 to 77777)

77777 (1.71 to 77777)

5.6 (1.64 to 77777)

14.2 (8.34 to 77777)

No statistical analyses for this end point

Secondary: Part A: Maximum Serum Concentration (Cmax) According to Antibody-Drug Conjugate (ADC) Pharmacokinetic Parameters

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End point title

Part A: Maximum Serum Concentration (Cmax) According to Antibody-Drug Conjugate (ADC) Pharmacokinetic Parameters ^[25]

End point description

Cmax according to ADC pharmacokinetic parameters was reported. The safety analysis set included all participants who received any amount of study drug.

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr, 168hr and 336hr post dose of Cycle 1 (each cycle = 21 days)

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	10	2	13	7	5	12
Units: Micrograms per millilitre
geometric mean (geometric coefficient of variation)	50.4 ( 31.2 )	58.6 ( 1.0 )	55.8 ( 29.6 )	52.3 ( 23.6 )	39.6 ( 14.7 )	55.2 ( 64.9 )

No statistical analyses for this end point

Secondary: Part A: Area Under the Serum Concentration Time Curve Between Days 0 to 21 (AUC21) of Ladiratuzumab Vedotin

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End point title

Part A: Area Under the Serum Concentration Time Curve Between Days 0 to 21 (AUC21) of Ladiratuzumab Vedotin ^[26]

End point description

Area under the observed concentration-time curve from the time of dosing to Day 21 of LV was calculated by noncompartmental analysis. The safety analysis set included all participants who received any amount of study drug. Here, 'Number of Participants Analysed (N)' signifies participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr, 168hr and 336hr post dose of Cycle 1 (each cycle = 21 days)

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	10	2	11	6	5	12
Units: Day*micrograms per millilitre
geometric mean (geometric coefficient of variation)	142.5 ( 18.9 )	175.6 ( 16.5 )	145.3 ( 35.1 )	146.6 ( 28.3 )	123.2 ( 21.7 )	132.0 ( 26.0 )

No statistical analyses for this end point

Secondary: Part A: AUC21 of Total Antibody (TAB)

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End point title

Part A: AUC21 of Total Antibody (TAB) ^[27]

End point description

Area under the observed concentration-time curve from the time of dosing to Day 21 of TAB was calculated by noncompartmental analysis. The safety analysis set included all participants who received any amount of study drug. Here, 'Number of Participants Analysed' signifies participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr, 168hr and 336hr post dose of Cycle 1 (each cycle = 21 days)

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	10	2	10	6	5	10
Units: Day*micrograms per millilitre
geometric mean (geometric coefficient of variation)	302.4 ( 19.7 )	328.5 ( 17.8 )	280.3 ( 34.1 )	292.3 ( 28.2 )	219.8 ( 28.5 )	258.9 ( 31.6 )

No statistical analyses for this end point

Secondary: Part A: Cmax According to TAB Pharmacokinetic Parameters

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End point title

Part A: Cmax According to TAB Pharmacokinetic Parameters ^[28]

End point description

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr, 168hr and 336hr post dose of Cycle 1 (each cycle = 21 days)

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	9	2	11	7	5	10
Units: Micrograms per millilitre
geometric mean (geometric coefficient of variation)	61.6 ( 23.7 )	66.1 ( 20.8 )	68.2 ( 30.5 )	61.4 ( 16.1 )	50.7 ( 38.3 )	57.2 ( 24.1 )

No statistical analyses for this end point

Secondary: Part A: Cmax According to MMAE Pharmacokinetic Parameters

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End point title

Part A: Cmax According to MMAE Pharmacokinetic Parameters ^[29]

End point description

Cmax according to MMAE pharmacokinetic parameters was reported. The safety analysis set included all participants who received any amount of study drug. Here, 'Number of Participants Analysed' signifies participants evaluable for this endpoint. 77777= insufficient number of participants to calculate the geometric coefficient of variation.

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr, 168hr and 336hr post dose of Cycle 1 (each cycle = 21 days)

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	2	1	7	2	2	6
Units: Nanogram per millilitre
geometric mean (geometric coefficient of variation)	2.8 ( 15.7 )	5.7 ( 77777 )	6.4 ( 83.1 )	6.3 ( 10.6 )	11.3 ( 12.6 )	3.6 ( 41.8 )

No statistical analyses for this end point

Secondary: Part A: AUC21 of Monomethyl Auristatin E (MMAE)

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End point title

Part A: AUC21 of Monomethyl Auristatin E (MMAE) ^[30]

End point description

Area under the observed concentration-time curve from the time of dosing to Day 21 of MMAE was calculated by noncompartmental analysis. The safety analysis set included all participants who received any amount of study drug. Here, 'Number of Participants Analysed' signifies participants evaluable for this endpoint. 77777= insufficient number of participants to calculate the geometric coefficient of variation.

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr, 168hr and 336hr post dose of Cycle 1 (each cycle = 21 days)

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	2	1	7	3	2	7
Units: Day*nanogram per milliliter
geometric mean (geometric coefficient of variation)	34.1 ( 21.1 )	50.5 ( 77777 )	62.9 ( 79.3 )	66.2 ( 45.6 )	91.0 ( 19.3 )	35.2 ( 36.9 )

No statistical analyses for this end point

Secondary: Part B: Area Under the Concentration Time Curve Between Day 0 to 7 (AUC7) of ADC

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End point title

Part B: Area Under the Concentration Time Curve Between Day 0 to 7 (AUC7) of ADC ^[31]

End point description

Area under the observed concentration-time curve from the time of dosing to Day 7 of ADC was calculated by noncompartmental analysis. The safety analysis set included all participants who received any amount of study drug. Here, 'Number of Participants Analysed' signifies participants evaluable for this endpoint. 77777= insufficient number of participants to calculate the geometric coefficient of variation. There were insufficient samples to provide pharmacokinetic (PK) estimates for analytes in Part B: Cohort 6, LV 1.0 mg/kg arm.

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose, and pre-dose on day 8 of Cycle 1 (each cycle = 21 days)

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part B: Cohort 1, LV 1.25 mg/kg	Part B: Cohort 2, LV 1.25 mg/kg	Part B: Cohort 3, LV 1.25 mg/kg	Part B: Cohort 4, LV 1.25 mg/kg	Part B: Cohort 5, LV 1.25 mg/kg	Part B: Cohort 6, LV 1.25 mg/kg	Part B: Cohort 7, LV 1.25 mg/kg	Part B: Cohort 8, LV 1.25 mg/kg	Part B: Cohort 1, LV 1.0 mg/kg	Part B: Cohort 3, LV 1.0 mg/kg	Part B: Cohort 4, LV 1.0 mg/kg	Part B: Cohort 6, LV 1.0 mg/kg
Number of subjects analysed	14	11	18	9	14	12	11	25	2	2	1	0 ^[32]
Units: Day*micrograms per millilitre
geometric mean (geometric coefficient of variation)	57.3 ( 23.2 )	51.7 ( 16.9 )	59.5 ( 29.7 )	60.6 ( 36.7 )	43.3 ( 12.6 )	50.7 ( 27.2 )	66.0 ( 42.8 )	46.8 ( 25.0 )	42.1 ( 0.5 )	52.0 ( 0.1 )	44.8 ( 77777 )	( )

Notes
[32] - There were insufficient samples to provide PK estimates for analytes for this arm.

No statistical analyses for this end point

Secondary: Part B: Cmax According to ADC Pharmacokinetic Parameters

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End point title

Part B: Cmax According to ADC Pharmacokinetic Parameters ^[33]

End point description

Cmax according to ADC pharmacokinetic parameters was reported. The safety analysis set included all participants who received any amount of study drug. Here, 'Number of Participants Analysed' signifies participants evaluable for this endpoint. There were insufficient samples to provide PK estimates for analytes in Part B: Cohort 6, LV 1.0 mg/kg arm.

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose and pre-dose and end of infusion on day 8 and 15 of Cycle 1 (each cycle = 21 days)

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

End point values	Part B: Cohort 1, LV 1.25 mg/kg	Part B: Cohort 2, LV 1.25 mg/kg	Part B: Cohort 3, LV 1.25 mg/kg	Part B: Cohort 4, LV 1.25 mg/kg	Part B: Cohort 5, LV 1.25 mg/kg	Part B: Cohort 6, LV 1.25 mg/kg	Part B: Cohort 7, LV 1.25 mg/kg	Part B: Cohort 8, LV 1.25 mg/kg	Part B: Cohort 1, LV 1.0 mg/kg	Part B: Cohort 3, LV 1.0 mg/kg	Part B: Cohort 4, LV 1.0 mg/kg	Part B: Cohort 6, LV 1.0 mg/kg
Number of subjects analysed	16	14	19	14	17	18	12	27	2	2	2	0 ^[34]
Units: Micrograms per millilitre
geometric mean (geometric coefficient of variation)	35.3 ( 35.0 )	27.8 ( 19.7 )	30.9 ( 19.2 )	28.7 ( 28.6 )	25.0 ( 28.8 )	28.0 ( 17.2 )	30.5 ( 15.1 )	25.4 ( 21.9 )	29.5 ( 20.3 )	24.3 ( 10.2 )	24.1 ( 6.2 )	( )

Notes
[34] - There were insufficient samples to provide PK estimates for analytes in this arm.

No statistical analyses for this end point

Secondary: Part B: AUC7 of TAB

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End point title

Part B: AUC7 of TAB ^[35]

End point description

Area under the observed concentration-time curve from the time of dosing to Day 7 of TAB was calculated by noncompartmental analysis. The safety analysis set included all participants who received any amount of study drug. Here, 'Number of Participants Analysed' signifies participants evaluable for this endpoint. 77777= insufficient number of participants to calculate the geometric coefficient of variation. There were insufficient samples to provide PK estimates for analytes in Part B: Cohort 6, LV 1.0 mg/kg arm.

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr post dose and pre-dose and end of infusion on day 8 and 15 of Cycle 1 (each cycle = 21 days)

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part B: Cohort 1, LV 1.25 mg/kg	Part B: Cohort 2, LV 1.25 mg/kg	Part B: Cohort 3, LV 1.25 mg/kg	Part B: Cohort 4, LV 1.25 mg/kg	Part B: Cohort 5, LV 1.25 mg/kg	Part B: Cohort 6, LV 1.25 mg/kg	Part B: Cohort 7, LV 1.25 mg/kg	Part B: Cohort 8, LV 1.25 mg/kg	Part B: Cohort 1, LV 1.0 mg/kg	Part B: Cohort 3, LV 1.0 mg/kg	Part B: Cohort 4, LV 1.0 mg/kg	Part B: Cohort 6, LV 1.0 mg/kg
Number of subjects analysed	14	11	18	9	14	12	11	25	2	2	1	0 ^[36]
Units: Day*micrograms per millilitre
geometric mean (geometric coefficient of variation)	101.1 ( 29.4 )	92.7 ( 18.7 )	106.9 ( 29.8 )	91.2 ( 30.9 )	73.9 ( 20.7 )	85.7 ( 26.0 )	106.5 ( 28.2 )	74.7 ( 26.3 )	76.6 ( 22.6 )	88.6 ( 11.1 )	71.4 ( 77777 )	( )

Notes
[36] - There were insufficient samples to provide PK estimates for analytes in this arm.

No statistical analyses for this end point

Secondary: Part B: Cmax According to TAB Pharmacokinetic Parameters

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End point title

Part B: Cmax According to TAB Pharmacokinetic Parameters ^[37]

End point description

Cmax according to TAB pharmacokinetic parameters was reported. The safety analysis set included all participants who received any amount of study drug. Here, 'Number of Participants Analysed' signifies participants evaluable for this endpoint. There were insufficient samples to provide PK estimates for analytes in Part B: Cohort 6, LV 1.0 mg/kg arm.

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose and pre-dose and end of infusion on day 8 and 15 of Cycle 1 (each cycle = 21 days)

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part B: Cohort 1, LV 1.25 mg/kg	Part B: Cohort 2, LV 1.25 mg/kg	Part B: Cohort 3, LV 1.25 mg/kg	Part B: Cohort 4, LV 1.25 mg/kg	Part B: Cohort 5, LV 1.25 mg/kg	Part B: Cohort 6, LV 1.25 mg/kg	Part B: Cohort 7, LV 1.25 mg/kg	Part B: Cohort 8, LV 1.25 mg/kg	Part B: Cohort 1, LV 1.0 mg/kg	Part B: Cohort 3, LV 1.0 mg/kg	Part B: Cohort 4, LV 1.0 mg/kg	Part B: Cohort 6, LV 1.0 mg/kg
Number of subjects analysed	16	14	19	14	17	17	12	29	2	2	2	0 ^[38]
Units: Micrograms per millilitre
geometric mean (geometric coefficient of variation)	38.3 ( 17.9 )	31.6 ( 16.6 )	36.8 ( 21.8 )	32.1 ( 26.2 )	27.4 ( 28.9 )	31.3 ( 19.7 )	32.6 ( 25.9 )	32.5 ( 73.8 )	26.8 ( 15.6 )	30.6 ( 14.8 )	27.9 ( 2.0 )	( )

Notes
[38] - There were insufficient samples to provide PK estimates for analytes in this arm.

No statistical analyses for this end point

Secondary: Part B: AUC7 OF MMAE

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End point title

Part B: AUC7 OF MMAE ^[39]

End point description

Area under the observed concentration-time curve from the time of dosing to Day 7 of MMAE was calculated by noncompartmental analysis. The safety analysis set included all participants who received any amount of study drug. Here, 'Number of Participants Analysed' signifies participants evaluable for this endpoint. 77777= insufficient number of participants to calculate the geometric coefficient of variation. There were insufficient samples to provide PK estimates for analytes in Part B: Cohort 6, LV 1.0 mg/kg arm.

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose and pre-dose and end of infusion on day 8 and 15 of Cycle 1 (each cycle = 21 days)

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part B: Cohort 1, LV 1.25 mg/kg	Part B: Cohort 2, LV 1.25 mg/kg	Part B: Cohort 3, LV 1.25 mg/kg	Part B: Cohort 4, LV 1.25 mg/kg	Part B: Cohort 5, LV 1.25 mg/kg	Part B: Cohort 6, LV 1.25 mg/kg	Part B: Cohort 7, LV 1.25 mg/kg	Part B: Cohort 8, LV 1.25 mg/kg	Part B: Cohort 1, LV 1.0 mg/kg	Part B: Cohort 3, LV 1.0 mg/kg	Part B: Cohort 4, LV 1.0 mg/kg	Part B: Cohort 6, LV 1.0 mg/kg
Number of subjects analysed	14	11	18	9	14	12	11	25	2	2	1	0 ^[40]
Units: Day*micrograms per millilitre
geometric mean (geometric coefficient of variation)	14.6 ( 63.1 )	16.5 ( 55.6 )	11.9 ( 51.5 )	15.6 ( 51.0 )	17.3 ( 67.6 )	13.7 ( 83.0 )	10.7 ( 57.3 )	13.8 ( 45.2 )	10.8 ( 64.1 )	12.4 ( 25.9 )	8.5 ( 77777 )	( )

Notes
[40] - There were insufficient samples to provide PK estimates for analytes in this arm.

No statistical analyses for this end point

Secondary: Part B: Cmax According to MMAE Pharmacokinetic Parameters

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End point title

Part B: Cmax According to MMAE Pharmacokinetic Parameters ^[41]

End point description

End point type

Secondary

End point timeframe

Pre-dose, end of infusion, 2hr, 4hr, 48hr post-dose and pre-dose and end of infusion on day 8 and 15 of Cycle 1 (each cycle = 21 days)

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part B: Cohort 1, LV 1.25 mg/kg	Part B: Cohort 2, LV 1.25 mg/kg	Part B: Cohort 3, LV 1.25 mg/kg	Part B: Cohort 4, LV 1.25 mg/kg	Part B: Cohort 5, LV 1.25 mg/kg	Part B: Cohort 6, LV 1.25 mg/kg	Part B: Cohort 7, LV 1.25 mg/kg	Part B: Cohort 8, LV 1.25 mg/kg	Part B: Cohort 1, LV 1.0 mg/kg	Part B: Cohort 3, LV 1.0 mg/kg	Part B: Cohort 4, LV 1.0 mg/kg	Part B: Cohort 6, LV 1.0 mg/kg
Number of subjects analysed	10	4	8	8	15	11	8	16	1	0 ^[42]	1	0 ^[43]
Units: Nanograms per millilitre
geometric mean (geometric coefficient of variation)	2.8 ( 60.7 )	4.5 ( 50.4 )	2.6 ( 59.1 )	2.7 ( 39.9 )	3.3 ( 65.8 )	2.9 ( 114.9 )	1.7 ( 28.9 )	2.4 ( 52.7 )	1.4 ( 77777 )	( )	1.7 ( 77777 )	( )

Notes
[42] - There were insufficient samples to provide PK estimates for analytes in this arm.
[43] - There were insufficient samples to provide PK estimates for analytes in this arm.

No statistical analyses for this end point

Secondary: Part A: Number of Participants With Positive Post-Baseline Antitherapeutic Antibody (ATA) Incidence

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End point title

Part A: Number of Participants With Positive Post-Baseline Antitherapeutic Antibody (ATA) Incidence ^[44]

End point description

A positive baseline ATA result was considered positive post-baseline if the post-baseline ATA titer result was at least four times higher than the baseline result. The safety analysis set included all participants who received any amount of study drug.

End point type

Secondary

End point timeframe

Anytime during study (maximum up to 8.8 months)

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part A: Cohort 1, LV 2.5 mg/kg	Part A: Cohort 2, LV 2.5 mg/kg	Part A: Cohort 3, LV 2.5 mg/kg	Part A: Cohort 4, LV 2.5 mg/kg	Part A: Cohort 5, LV 2.5 mg/kg	Part A: Cohort 6, LV 2.5 mg/kg
Number of subjects analysed	10	2	13	7	5	12
Units: Participants
Baseline Negative\|Positive post-baseline	1	0	1	1	0	1
Baseline Positive\|Positive post-baseline	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Part B: Number of Participants With Positive Post-Baseline ATA Incidence

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End point title

Part B: Number of Participants With Positive Post-Baseline ATA Incidence ^[45]

End point description

End point type

Secondary

End point timeframe

Anytime during study (maximum up to 22.1 months for 1.25 mg/kg and 5.1 months for 1 mg/kg)

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be analysed only for the specified reporting arms.

End point values	Part B: Cohort 1, LV 1.25 mg/kg	Part B: Cohort 2, LV 1.25 mg/kg	Part B: Cohort 3, LV 1.25 mg/kg	Part B: Cohort 4, LV 1.25 mg/kg	Part B: Cohort 5, LV 1.25 mg/kg	Part B: Cohort 6, LV 1.25 mg/kg	Part B: Cohort 7, LV 1.25 mg/kg	Part B: Cohort 8, LV 1.25 mg/kg	Part B: Cohort 1, LV 1.0 mg/kg	Part B: Cohort 3, LV 1.0 mg/kg	Part B: Cohort 4, LV 1.0 mg/kg	Part B: Cohort 6, LV 1.0 mg/kg
Number of subjects analysed	16	16	19	14	17	21	13	30	2	2	2	2
Units: Participants
Baseline Negative\|Positive post-baseline	1	1	4	0	2	1	1	4	0	2	0	0
Baseline Positive\|Positive post-baseline	0	1	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From start of study treatment up to 30 days after last dose of study treatment (maximum up to 37.5 months)

Adverse event reporting additional description

Same event may appear as both AE and SAE. What is presented are distinct events. Event may be categorised as serious in one participant and non-serious in another, or participant may have experienced both serious and non-serious event. All-cause mortality included all enrolled participants. SAEs and non-SAEs were analysed in safety analysis set.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

v26.1

Reporting group title

Part A 2.5 mg/kg: Esophageal-squamous

Reporting group description

Part A 2.5 mg/kg: Esophageal-squamous

Reporting group title

Part A 2.5 mg/kg: HNSCC

Reporting group description

Part A 2.5 mg/kg: HNSCC

Reporting group title

Part A 2.5 mg/kg: NSCLC-nonsquamous

Reporting group description

Part A 2.5 mg/kg: NSCLC-nonsquamous

Reporting group title

Part A 2.5 mg/kg: NSCLC-squamous

Reporting group description

Part A 2.5 mg/kg: NSCLC-squamous

Reporting group title

Part A 2.5 mg/kg: SCLC

Reporting group description

Part A 2.5 mg/kg: SCLC

Reporting group title

Part A 2.5 mg/kg: Gastric and GEJ

Reporting group description

Part A 2.5 mg/kg: Gastric and GEJ

Reporting group title

Part B 1.25 mg/kg: Prostate Cancer

Reporting group description

Part B 1.25 mg/kg: Prostate Cancer

Reporting group title

Part B 1.25 mg/kg: Melanoma

Reporting group description

Part B 1.25 mg/kg: Melanoma

Reporting group title

Part B 1.0 mg/kg: SCLC

Reporting group description

Part B 1.0 mg/kg: SCLC

Reporting group title

Part B 1.0 mg/kg: NSCLC-nonsquamous

Reporting group description

Part B 1.0 mg/kg: NSCLC-nonsquamous

Reporting group title

Part B 1.0 mg/kg: HNSCC

Reporting group description

Part B 1.0 mg/kg: HNSCC

Reporting group title

Part B 1.25 mg/kg: Gastric and GEJ

Reporting group description

Part B 1.25 mg/kg: Gastric and GEJ

Reporting group title

Part B 1.25 mg/kg: Esophageal-squamous

Reporting group description

Part B 1.25 mg/kg: Esophageal-squamous

Reporting group title

Part B 1.25 mg/kg: HNSCC

Reporting group description

Part B 1.25 mg/kg: HNSCC

Reporting group title

Part B 1.0 mg/kg: Gastric and GEJ

Reporting group description

Part B 1.0 mg/kg: Gastric and GEJ

Reporting group title

Part B 1.25 mg/kg: NSCLC-squamous

Reporting group description

Part B 1.25 mg/kg: NSCLC-squamous

Reporting group title

Part B 1.25 mg/kg: SCLC

Reporting group description

Part B 1.25 mg/kg: SCLC

Reporting group title

Part B 1.25 mg/kg: NSCLC-nonsquamous

Reporting group description

Part B 1.25 mg/kg: NSCLC-nonsquamous

Part A 2.5 mg/kg: Esophageal-squamous

Part A 2.5 mg/kg: HNSCC

Part A 2.5 mg/kg: NSCLC-nonsquamous

Part A 2.5 mg/kg: NSCLC-squamous

Part A 2.5 mg/kg: SCLC

Part A 2.5 mg/kg: Gastric and GEJ

Part B 1.25 mg/kg: Prostate Cancer

Part B 1.25 mg/kg: Melanoma

Part B 1.0 mg/kg: SCLC

Part B 1.0 mg/kg: NSCLC-nonsquamous

Part B 1.0 mg/kg: HNSCC

Part B 1.25 mg/kg: Gastric and GEJ

Part B 1.25 mg/kg: Esophageal-squamous

Part B 1.25 mg/kg: HNSCC

Part B 1.0 mg/kg: Gastric and GEJ

Part B 1.25 mg/kg: NSCLC-squamous

Part B 1.25 mg/kg: SCLC

Part B 1.25 mg/kg: NSCLC-nonsquamous

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 5 (60.00%)

2 / 7 (28.57%)

7 / 13 (53.85%)

1 / 2 (50.00%)

5 / 10 (50.00%)

3 / 12 (25.00%)

4 / 13 (30.77%)

10 / 30 (33.33%)

1 / 2 (50.00%)

2 / 2 (100.00%)

1 / 2 (50.00%)

12 / 21 (57.14%)

9 / 17 (52.94%)

8 / 14 (57.14%)

0 / 2 (0.00%)

5 / 16 (31.25%)

6 / 16 (37.50%)

9 / 19 (47.37%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Lymphangiosis carcinomatosa

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Tumour haemorrhage

subjects affected / exposed

0 / 5 (0.00%)

2 / 7 (28.57%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

Vascular disorders

Hypotension

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Asthenia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

3 / 12 (25.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

2 / 21 (9.52%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

2 / 5

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

2 / 4

0 / 0

1 / 1

0 / 0

Complication associated with device

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Fatigue

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

Multiple organ dysfunction syndrome

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Non-cardiac chest pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oedema peripheral

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (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

Pyrexia

subjects affected / exposed

0 / 5 (0.00%)

1 / 7 (14.29%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

Bronchial obstruction

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Dyspnoea

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Haemoptysis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Hypoxia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Pharyngeal haemorrhage

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oropharyngeal pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

Interstitial lung disease

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

Pneumonitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

2 / 13 (15.38%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

2 / 17 (11.76%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

1 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

Pneumothorax

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

1 / 2 (50.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Productive cough

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Pulmonary embolism

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

Respiratory distress

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

Respiratory failure

subjects affected / exposed

1 / 5 (20.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

1 / 2 (50.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

Psychiatric disorders

Mental status changes

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Investigations

Brain natriuretic peptide increased

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neutrophil count decreased

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Fall

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Overdose

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Congenital, familial and genetic disorders

Laryngocele

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Cardiac disorders

Acute myocardial infarction

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac arrest

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

2 / 19 (10.53%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 2

Myocardial infarction

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pericardial effusion

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Stress cardiomyopathy

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Acute motor-sensory axonal neuropathy

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebrovascular accident

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Dizziness

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Encephalopathy

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (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

Haemorrhage intracranial

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Metabolic encephalopathy

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Petit mal epilepsy

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal cord compression

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Seizure

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Syncope

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Vocal cord paralysis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Febrile neutropenia

subjects affected / exposed

1 / 5 (20.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

Anaemia

subjects affected / exposed

0 / 5 (0.00%)

1 / 7 (14.29%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 2

0 / 0

0 / 1

Neutropenia

subjects affected / exposed

0 / 5 (0.00%)

1 / 7 (14.29%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Leukocytosis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

3 / 21 (14.29%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 3

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

0 / 1

Abdominal pain lower

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

1 / 16 (6.25%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal pain upper

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Colitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

Constipation

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

2 / 30 (6.67%)

0 / 2 (0.00%)

1 / 2 (50.00%)

2 / 21 (9.52%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

0 / 1

1 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

Diarrhoea

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

1 / 17 (5.88%)

1 / 14 (7.14%)

0 / 2 (0.00%)

1 / 16 (6.25%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

1 / 1

0 / 0

1 / 1

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Dysphagia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Gastrooesophageal reflux disease

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

Ileus

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal obstruction

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Nausea

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Oesophageal pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Oesophageal fistula

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Stomatitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Small intestinal perforation

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

Skin and subcutaneous tissue disorders

Erythema multiforme

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

1 / 16 (6.25%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Hydronephrosis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

Inappropriate antidiuretic hormone secretion

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (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

Adrenal insufficiency

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Arthralgia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Back pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Myalgia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

2 / 10 (20.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

2 / 2

0 / 0

Mobility decreased

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (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

Infections and infestations

Arthritis bacterial

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Biliary sepsis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Biliary tract infection

subjects affected / exposed

1 / 5 (20.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Bronchitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Conjunctivitis bacterial

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Device related infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Infection

subjects affected / exposed

1 / 5 (20.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Periorbital cellulitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Liver abscess

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Pneumonia

subjects affected / exposed

1 / 5 (20.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

1 / 30 (3.33%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

1 / 14 (7.14%)

0 / 2 (0.00%)

1 / 16 (6.25%)

0 / 16 (0.00%)

2 / 19 (10.53%)

occurrences causally related to treatment / all

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

Pneumonia aspiration

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

1 / 1

0 / 0

Staphylococcal infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Urinary tract infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

1 / 14 (7.14%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Staphylococcal sepsis

subjects affected / exposed

0 / 5 (0.00%)

1 / 7 (14.29%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Metabolism and nutrition disorders

Decreased appetite

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

1 / 21 (4.76%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (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

Dehydration

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 13 (7.69%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 13 (7.69%)

1 / 30 (3.33%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

2 / 19 (10.53%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 2

1 / 1

Hyperglycaemia

subjects affected / exposed

0 / 5 (0.00%)

1 / 7 (14.29%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Failure to thrive

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Hypokalaemia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

0 / 17 (0.00%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

1 / 16 (6.25%)

0 / 19 (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

Hyponatraemia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 13 (0.00%)

0 / 2 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 13 (0.00%)

0 / 30 (0.00%)

0 / 2 (0.00%)

0 / 21 (0.00%)

1 / 17 (5.88%)

0 / 14 (0.00%)

0 / 2 (0.00%)

0 / 16 (0.00%)

2 / 16 (12.50%)

0 / 19 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

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

Non-serious adverse events	Part A 2.5 mg/kg: Esophageal-squamous	Part A 2.5 mg/kg: HNSCC	Part A 2.5 mg/kg: NSCLC-nonsquamous	Part A 2.5 mg/kg: NSCLC-squamous	Part A 2.5 mg/kg: SCLC	Part A 2.5 mg/kg: Gastric and GEJ	Part B 1.25 mg/kg: Prostate Cancer	Part B 1.25 mg/kg: Melanoma	Part B 1.0 mg/kg: SCLC	Part B 1.0 mg/kg: NSCLC-nonsquamous	Part B 1.0 mg/kg: HNSCC	Part B 1.25 mg/kg: Gastric and GEJ	Part B 1.25 mg/kg: Esophageal-squamous	Part B 1.25 mg/kg: HNSCC	Part B 1.0 mg/kg: Gastric and GEJ	Part B 1.25 mg/kg: NSCLC-squamous	Part B 1.25 mg/kg: SCLC	Part B 1.25 mg/kg: NSCLC-nonsquamous
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 5 (100.00%)	6 / 7 (85.71%)	13 / 13 (100.00%)	2 / 2 (100.00%)	10 / 10 (100.00%)	12 / 12 (100.00%)	13 / 13 (100.00%)	30 / 30 (100.00%)	2 / 2 (100.00%)	2 / 2 (100.00%)	2 / 2 (100.00%)	19 / 21 (90.48%)	17 / 17 (100.00%)	14 / 14 (100.00%)	2 / 2 (100.00%)	16 / 16 (100.00%)	15 / 16 (93.75%)	19 / 19 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Cancer pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 21 (9.52%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0
Hypotension
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	2 / 10 (20.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1	0	2	0	0	2	0	0	1	0	1	0	0	0	0	4
Arterial occlusive disease
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Flushing
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1
Hypertension
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	1 / 2 (50.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	3 / 30 (10.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1	1	0	0	0	3	0	0	0	1	0	1	0	0	0	1
Raynaud's phenomenon
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 5 (0.00%)	2 / 7 (28.57%)	2 / 13 (15.38%)	1 / 2 (50.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	2 / 13 (15.38%)	4 / 30 (13.33%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	2 / 14 (14.29%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	2 / 19 (10.53%)
occurrences all number	0	2	2	1	1	1	2	6	1	0	0	0	0	2	0	0	1	2
Fatigue
subjects affected / exposed	2 / 5 (40.00%)	5 / 7 (71.43%)	10 / 13 (76.92%)	0 / 2 (0.00%)	1 / 10 (10.00%)	2 / 12 (16.67%)	7 / 13 (53.85%)	13 / 30 (43.33%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	11 / 21 (52.38%)	12 / 17 (70.59%)	7 / 14 (50.00%)	1 / 2 (50.00%)	9 / 16 (56.25%)	7 / 16 (43.75%)	12 / 19 (63.16%)
occurrences all number	2	5	10	0	1	2	8	18	1	0	0	12	12	7	1	11	8	13
Oedema peripheral
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	3 / 30 (10.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	3 / 19 (15.79%)
occurrences all number	0	0	2	0	0	0	1	3	0	0	0	1	2	0	0	0	1	4
Pyrexia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	3 / 30 (10.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	2 / 17 (11.76%)	5 / 14 (35.71%)	1 / 2 (50.00%)	0 / 16 (0.00%)	5 / 16 (31.25%)	2 / 19 (10.53%)
occurrences all number	0	0	1	0	1	1	0	7	0	1	0	0	3	5	1	0	6	2
Chest pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Chills
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	2
Face oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Gait disturbance
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	1	0	1
Influenza like illness
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1
Injection site irritation
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Localised oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	2 / 14 (14.29%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	3	1	0	0	0	0	1	2	0	0	1	0
Oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0
Pain
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	2 / 14 (14.29%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	1	1	0	0	0	0	0	2	0	0	0	0
Swelling face
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Swelling
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Peripheral swelling
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Immune system disorders
Seasonal allergy
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Reproductive system and breast disorders
Genital burning sensation
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	2 / 5 (40.00%)	0 / 7 (0.00%)	4 / 13 (30.77%)	0 / 2 (0.00%)	3 / 10 (30.00%)	1 / 12 (8.33%)	3 / 13 (23.08%)	1 / 30 (3.33%)	2 / 2 (100.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	3 / 17 (17.65%)	1 / 14 (7.14%)	0 / 2 (0.00%)	4 / 16 (25.00%)	4 / 16 (25.00%)	5 / 19 (26.32%)
occurrences all number	2	0	4	0	3	2	3	1	2	0	0	1	4	1	0	4	5	5
Haemoptysis
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	2
Productive cough
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	2 / 12 (16.67%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	2 / 19 (10.53%)
occurrences all number	0	0	0	0	1	2	0	0	0	0	0	0	1	0	0	0	2	2
Cough
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 13 (15.38%)	0 / 2 (0.00%)	2 / 10 (20.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	3 / 14 (21.43%)	0 / 2 (0.00%)	2 / 16 (12.50%)	1 / 16 (6.25%)	4 / 19 (21.05%)
occurrences all number	0	0	2	0	2	0	1	2	0	0	0	1	1	3	0	2	1	4
Pulmonary embolism
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	1	1	0	0	1	0	1
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Aspiration
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Dysphonia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Dyspnoea exertional
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0	0	0	1	1	0	0	0	0	0	1	0	1	0	0
Haemothorax
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hiccups
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	1
Hypoxia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0	0	0	1	0	1	0	2
Laryngeal inflammation
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Laryngeal ventricle prolapse
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1
Pleural effusion
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	1	0	0	2	2
Pneumonitis
subjects affected / exposed	2 / 5 (40.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	2	0	0	0	0	0	1	1	0	0	0	1	1	0	0	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1
Rhinitis allergic
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Wheezing
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1	1	0	0	0	0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 13 (15.38%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	2	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Anxiety
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 13 (15.38%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	2 / 13 (15.38%)	0 / 30 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	2	0	2	0	2	0	0	1	0	1	0	1	0	0	0	1
Insomnia
subjects affected / exposed	2 / 5 (40.00%)	1 / 7 (14.29%)	2 / 13 (15.38%)	0 / 2 (0.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	4 / 13 (30.77%)	6 / 30 (20.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	4 / 21 (19.05%)	3 / 17 (17.65%)	2 / 14 (14.29%)	0 / 2 (0.00%)	1 / 16 (6.25%)	2 / 16 (12.50%)	3 / 19 (15.79%)
occurrences all number	2	1	2	0	1	1	5	6	0	1	0	4	3	2	0	1	2	3
Depression
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	1	1	0	0	0	2
Hallucination
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Delirium
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0
Poor quality sleep
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	1 / 5 (20.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	3 / 13 (23.08%)	8 / 30 (26.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	3 / 21 (14.29%)	1 / 17 (5.88%)	2 / 14 (14.29%)	0 / 2 (0.00%)	2 / 16 (12.50%)	2 / 16 (12.50%)	1 / 19 (5.26%)
occurrences all number	1	1	0	0	1	1	3	11	0	0	0	3	1	2	0	3	2	2
Alanine aminotransferase increased
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	2 / 13 (15.38%)	10 / 30 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 21 (9.52%)	1 / 17 (5.88%)	1 / 14 (7.14%)	0 / 2 (0.00%)	2 / 16 (12.50%)	2 / 16 (12.50%)	1 / 19 (5.26%)
occurrences all number	1	0	0	0	1	1	3	11	0	0	0	2	1	1	0	2	2	1
Weight decreased
subjects affected / exposed	1 / 5 (20.00%)	1 / 7 (14.29%)	3 / 13 (23.08%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	7 / 30 (23.33%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	4 / 21 (19.05%)	6 / 17 (35.29%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	3 / 16 (18.75%)	3 / 19 (15.79%)
occurrences all number	1	1	3	0	1	0	0	8	0	1	0	4	6	0	0	0	3	3
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Blood creatinine increased
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 21 (9.52%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	1	0	0	0	0	1	1	0	0	0	3	0	0	0	0	0	1
Blood magnesium decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0
International normalised ratio increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	2 / 16 (12.50%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1
Iron binding capacity total decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Liver function test increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Lymphocyte count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Neutrophil count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 21 (9.52%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	2 / 16 (12.50%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	5	0	0	0	0	4	0
Troponin increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Weight increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
White blood cell count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	2 / 16 (12.50%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	4	1
Injury, poisoning and procedural complications
Burns first degree
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin abrasion
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Infusion related reaction
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Fall
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	2 / 16 (12.50%)	2 / 19 (10.53%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	2	2
Craniocerebral injury
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Clavicle fracture
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 13 (15.38%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	1 / 2 (50.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	2	0	0	0	0	2	0	0	1	0	0	0	1	0	0	1
Tachycardia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	2
Pericardial effusion
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	1
Palpitations
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0
Atrial fibrillation
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	1 / 2 (50.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	2 / 10 (20.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	4 / 30 (13.33%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	1 / 14 (7.14%)	0 / 2 (0.00%)	2 / 16 (12.50%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	2	1	0	6	1	0	0	1	1	1	0	3	1	0
Dizziness
subjects affected / exposed	1 / 5 (20.00%)	1 / 7 (14.29%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	2 / 13 (15.38%)	1 / 30 (3.33%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	2 / 17 (11.76%)	0 / 14 (0.00%)	0 / 2 (0.00%)	2 / 16 (12.50%)	0 / 16 (0.00%)	3 / 19 (15.79%)
occurrences all number	1	1	2	0	0	1	2	2	1	0	0	0	2	0	0	2	0	4
Disturbance in attention
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Sciatica
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Peripheral sensory neuropathy
subjects affected / exposed	2 / 5 (40.00%)	1 / 7 (14.29%)	3 / 13 (23.08%)	0 / 2 (0.00%)	1 / 10 (10.00%)	3 / 12 (25.00%)	3 / 13 (23.08%)	15 / 30 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	7 / 21 (33.33%)	3 / 17 (17.65%)	8 / 14 (57.14%)	0 / 2 (0.00%)	4 / 16 (25.00%)	1 / 16 (6.25%)	7 / 19 (36.84%)
occurrences all number	2	1	3	0	3	3	4	17	0	0	0	7	3	8	0	5	1	7
Paraesthesia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	2 / 13 (15.38%)	4 / 30 (13.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	3 / 16 (18.75%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	1	0	0	1	2	6	0	0	0	1	0	0	0	3	0	2
Amnesia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Asterixis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Aphasia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dizziness postural
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Dysgeusia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 21 (9.52%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0	3	1	0	0	0	0	0
Dysarthria
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypoaesthesia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hypogeusia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lethargy
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Lumbar radiculopathy
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Memory impairment
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Neuralgia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1
Neurotoxicity
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Seizure
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Peripheral motor neuropathy
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	2	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0
Peripheral sensorimotor neuropathy
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0
Syncope
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Taste disorder
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Transient ischaemic attack
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Tremor
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 5 (20.00%)	1 / 7 (14.29%)	2 / 13 (15.38%)	0 / 2 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	1 / 13 (7.69%)	7 / 30 (23.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	6 / 21 (28.57%)	2 / 17 (11.76%)	2 / 14 (14.29%)	1 / 2 (50.00%)	0 / 16 (0.00%)	2 / 16 (12.50%)	2 / 19 (10.53%)
occurrences all number	1	1	2	0	0	3	1	8	0	0	1	8	4	2	1	0	3	3
Neutropenia
subjects affected / exposed	3 / 5 (60.00%)	1 / 7 (14.29%)	1 / 13 (7.69%)	0 / 2 (0.00%)	2 / 10 (20.00%)	4 / 12 (33.33%)	5 / 13 (38.46%)	8 / 30 (26.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 21 (9.52%)	6 / 17 (35.29%)	1 / 14 (7.14%)	0 / 2 (0.00%)	2 / 16 (12.50%)	3 / 16 (18.75%)	3 / 19 (15.79%)
occurrences all number	4	2	1	0	2	6	8	10	0	0	0	3	8	3	0	5	3	3
Leukocytosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Lymphopenia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0
Leukopenia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	2 / 14 (14.29%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	0	0	1	0	0	4	0	0	0	1	0	2	0	0	0	3
Febrile neutropenia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Anaemia macrocytic
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	1	1	0	0	0	1	0	0	0	0	0	0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Eye disorders
Cataract
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Visual impairment
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 5 (0.00%)	2 / 7 (28.57%)	1 / 13 (7.69%)	0 / 2 (0.00%)	3 / 10 (30.00%)	4 / 12 (33.33%)	2 / 13 (15.38%)	8 / 30 (26.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	6 / 21 (28.57%)	4 / 17 (23.53%)	1 / 14 (7.14%)	0 / 2 (0.00%)	2 / 16 (12.50%)	1 / 16 (6.25%)	3 / 19 (15.79%)
occurrences all number	0	2	1	0	3	5	4	10	0	0	0	7	6	1	0	2	1	3
Abdominal pain upper
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1	0	0	2	0	4	0	0	0	0	0	1	0	0	0	1
Constipation
subjects affected / exposed	2 / 5 (40.00%)	1 / 7 (14.29%)	4 / 13 (30.77%)	2 / 2 (100.00%)	2 / 10 (20.00%)	4 / 12 (33.33%)	4 / 13 (30.77%)	13 / 30 (43.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	5 / 21 (23.81%)	6 / 17 (35.29%)	3 / 14 (21.43%)	1 / 2 (50.00%)	4 / 16 (25.00%)	2 / 16 (12.50%)	4 / 19 (21.05%)
occurrences all number	2	2	4	2	2	4	6	13	0	0	0	6	8	4	1	4	2	6
Diarrhoea
subjects affected / exposed	2 / 5 (40.00%)	3 / 7 (42.86%)	6 / 13 (46.15%)	0 / 2 (0.00%)	0 / 10 (0.00%)	4 / 12 (33.33%)	4 / 13 (30.77%)	14 / 30 (46.67%)	1 / 2 (50.00%)	0 / 2 (0.00%)	2 / 2 (100.00%)	8 / 21 (38.10%)	5 / 17 (29.41%)	5 / 14 (35.71%)	1 / 2 (50.00%)	9 / 16 (56.25%)	6 / 16 (37.50%)	6 / 19 (31.58%)
occurrences all number	2	3	9	0	0	4	6	24	1	0	2	11	7	5	2	17	8	11
Dyspepsia
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	2 / 13 (15.38%)	3 / 30 (10.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 21 (9.52%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	1	0	0	1	0	2	3	0	0	0	2	0	0	0	0	0	1
Gastrointestinal pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 5 (20.00%)	3 / 7 (42.86%)	8 / 13 (61.54%)	1 / 2 (50.00%)	3 / 10 (30.00%)	3 / 12 (25.00%)	4 / 13 (30.77%)	16 / 30 (53.33%)	1 / 2 (50.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	9 / 21 (42.86%)	8 / 17 (47.06%)	6 / 14 (42.86%)	0 / 2 (0.00%)	7 / 16 (43.75%)	6 / 16 (37.50%)	11 / 19 (57.89%)
occurrences all number	1	3	10	1	6	4	4	22	1	1	0	11	9	7	0	8	8	13
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	4 / 19 (21.05%)
occurrences all number	0	0	0	0	0	0	2	1	0	0	0	1	0	1	0	1	0	4
Stomatitis
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	2 / 13 (15.38%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	2 / 21 (9.52%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)
occurrences all number	1	0	2	0	0	0	0	0	0	1	0	2	0	1	0	0	1	1
Vomiting
subjects affected / exposed	1 / 5 (20.00%)	1 / 7 (14.29%)	4 / 13 (30.77%)	0 / 2 (0.00%)	2 / 10 (20.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	8 / 30 (26.67%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	6 / 21 (28.57%)	3 / 17 (17.65%)	2 / 14 (14.29%)	0 / 2 (0.00%)	3 / 16 (18.75%)	2 / 16 (12.50%)	7 / 19 (36.84%)
occurrences all number	1	1	7	0	3	1	0	8	0	1	0	6	3	2	0	5	2	12
Abdominal discomfort
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	2
Abdominal distension
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	2
Abdominal pain lower
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	1 / 2 (50.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	1	0	0	0	2	0	0	0	0	0	1	0	0	0	0
Ascites
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 21 (9.52%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Dry mouth
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	2 / 19 (10.53%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	1	1	1	0	0	1	2
Dysphagia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	2 / 17 (11.76%)	2 / 14 (14.29%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	2	2	0	0	0	0
Haematochezia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Flatulence
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0
Gastritis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	1	0	0	0	0
Hiatus hernia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Retching
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Swollen tongue
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Melaena
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Odynophagia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Oesophagitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Oral pain
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tongue ulceration
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hepatobiliary disorders
Hypertransaminasaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	1
Hyperbilirubinaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Jaundice
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	1 / 5 (20.00%)	4 / 7 (57.14%)	5 / 13 (38.46%)	0 / 2 (0.00%)	3 / 10 (30.00%)	7 / 12 (58.33%)	4 / 13 (30.77%)	17 / 30 (56.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	7 / 21 (33.33%)	7 / 17 (41.18%)	4 / 14 (28.57%)	0 / 2 (0.00%)	5 / 16 (31.25%)	3 / 16 (18.75%)	5 / 19 (26.32%)
occurrences all number	1	4	5	0	3	7	4	18	0	0	0	7	7	4	0	5	3	5
Hyperhidrosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 13 (15.38%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	3 / 21 (14.29%)	0 / 17 (0.00%)	2 / 14 (14.29%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	2	0	0	1	0	1	0	0	0	3	0	2	0	0	0	3
Pruritus
subjects affected / exposed	1 / 5 (20.00%)	1 / 7 (14.29%)	1 / 13 (7.69%)	1 / 2 (50.00%)	2 / 10 (20.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	4 / 30 (13.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	3 / 17 (17.65%)	1 / 14 (7.14%)	0 / 2 (0.00%)	1 / 16 (6.25%)	1 / 16 (6.25%)	2 / 19 (10.53%)
occurrences all number	1	1	1	1	3	1	0	7	0	0	0	0	3	1	0	3	1	2
Dermatitis acneiform
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Dermatitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0
Decubitus ulcer
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dry skin
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	1 / 16 (6.25%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1
Erythema
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	1	0	0	0	1	0
Rash maculo-papular
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	1	0	0	0	0	0	0
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	2 / 13 (15.38%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	1	0
Erythema multiforme
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Rash papular
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Skin maceration
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Skin hyperpigmentation
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin toxicity
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Skin ulcer
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0	1	0	0	1	0	0	0	0	1	0	0	0	0	0
Urticaria
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	4	0	0	0	0	0	0	0	0	0	0	0	0
Renal and urinary disorders
Chromaturia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Acute kidney injury
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dysuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0	1	1	0	0	0	0	1	0	0	0	1	0
Haematuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Hydronephrosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0
Micturition urgency
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Nephrolithiasis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pollakiuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0
Urinary retention
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Endocrine disorders
Androgen deficiency
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Adrenal insufficiency
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	1	0	0
Hyperprolactinaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hypothyroidism
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 5 (20.00%)	2 / 7 (28.57%)	2 / 13 (15.38%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	2 / 13 (15.38%)	5 / 30 (16.67%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	3 / 21 (14.29%)	2 / 17 (11.76%)	2 / 14 (14.29%)	0 / 2 (0.00%)	3 / 16 (18.75%)	3 / 16 (18.75%)	3 / 19 (15.79%)
occurrences all number	1	2	2	0	1	0	2	6	1	0	0	3	2	2	0	3	3	4
Back pain
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	1 / 2 (50.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	6 / 30 (20.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	2 / 14 (14.29%)	0 / 2 (0.00%)	1 / 16 (6.25%)	1 / 16 (6.25%)	1 / 19 (5.26%)
occurrences all number	0	1	0	1	1	0	0	6	0	1	1	1	1	2	0	1	1	2
Muscular weakness
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	3 / 13 (23.08%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	3	2	0	0	0	1	1	0	0	0	1	1
Myalgia
subjects affected / exposed	2 / 5 (40.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	2 / 12 (16.67%)	1 / 13 (7.69%)	5 / 30 (16.67%)	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	3 / 14 (21.43%)	0 / 2 (0.00%)	2 / 16 (12.50%)	3 / 16 (18.75%)	2 / 19 (10.53%)
occurrences all number	3	0	0	0	1	2	1	10	1	0	1	2	2	3	0	2	3	2
Pain in extremity
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	3 / 30 (10.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	2 / 17 (11.76%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	3 / 19 (15.79%)
occurrences all number	0	0	1	0	0	0	1	4	0	0	0	0	2	0	0	1	0	3
Neck pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	1	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2
Muscle spasms
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Groin pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1
Bone pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	2 / 16 (12.50%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	1	1	0	0	0	0	0	1	0	0	2	1	0
Bursitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Soft tissue necrosis
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pain in jaw
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	1	0	0	0	0	0	0
Musculoskeletal discomfort
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Infections and infestations
Conjunctivitis bacterial
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Gingivitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	1 / 2 (50.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Oral candidiasis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	2 / 14 (14.29%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	0	0	0	0	1	2	0	0	0	1	1	2	0	0	0	2
Pneumonia
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	2 / 14 (14.29%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	1	0	0	1	0	1	0	1	0	0	1	2	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	1 / 2 (50.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Bronchitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
COVID-19
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	3 / 30 (10.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Escherichia infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Herpes simplex
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Lymphangitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Oral fungal infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Pneumonia aspiration
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Rash pustular
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	1	0	0	0	1	0
Urinary tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	2 / 13 (15.38%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0	0	0	1	1	0	0	0	0	0
Tooth infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Tooth abscess
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Sputum purulent
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 5 (0.00%)	2 / 7 (28.57%)	4 / 13 (30.77%)	1 / 2 (50.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	2 / 13 (15.38%)	1 / 30 (3.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	2 / 14 (14.29%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	2 / 19 (10.53%)
occurrences all number	0	2	4	1	1	0	2	1	0	0	0	0	1	2	0	0	2	2
Decreased appetite
subjects affected / exposed	3 / 5 (60.00%)	4 / 7 (57.14%)	6 / 13 (46.15%)	0 / 2 (0.00%)	3 / 10 (30.00%)	2 / 12 (16.67%)	6 / 13 (46.15%)	11 / 30 (36.67%)	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	8 / 21 (38.10%)	10 / 17 (58.82%)	6 / 14 (42.86%)	2 / 2 (100.00%)	2 / 16 (12.50%)	7 / 16 (43.75%)	5 / 19 (26.32%)
occurrences all number	3	5	6	0	3	2	6	12	1	0	1	9	12	6	2	2	7	6
Hypercalcaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	1 / 16 (6.25%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	1	0	0	1	0	0
Hyperglycaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	2 / 10 (20.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	6 / 30 (20.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	1 / 2 (50.00%)	5 / 16 (31.25%)	1 / 16 (6.25%)	2 / 19 (10.53%)
occurrences all number	0	0	1	0	3	0	1	9	0	0	0	1	0	0	1	6	1	2
Hypokalaemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	4 / 13 (30.77%)	1 / 2 (50.00%)	3 / 10 (30.00%)	1 / 12 (8.33%)	3 / 13 (23.08%)	1 / 30 (3.33%)	0 / 2 (0.00%)	2 / 2 (100.00%)	0 / 2 (0.00%)	2 / 21 (9.52%)	1 / 17 (5.88%)	2 / 14 (14.29%)	1 / 2 (50.00%)	2 / 16 (12.50%)	3 / 16 (18.75%)	5 / 19 (26.32%)
occurrences all number	1	0	5	1	3	1	3	1	0	3	0	2	1	4	1	2	6	7
Hypomagnesaemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	4 / 13 (30.77%)	0 / 2 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	2 / 13 (15.38%)	0 / 30 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	2 / 14 (14.29%)	0 / 2 (0.00%)	2 / 16 (12.50%)	4 / 16 (25.00%)	3 / 19 (15.79%)
occurrences all number	1	0	4	0	1	0	2	0	0	1	0	0	1	3	0	2	4	5
Hyponatraemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 13 (15.38%)	0 / 2 (0.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	1 / 30 (3.33%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	2 / 17 (11.76%)	1 / 14 (7.14%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	4 / 19 (21.05%)
occurrences all number	0	0	2	0	1	1	0	1	1	0	0	2	2	1	0	0	1	4
Abnormal loss of weight
subjects affected / exposed	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gout
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cachexia
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypercreatininaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hypermagnesaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hyperkalaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 13 (7.69%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	2	0
Malnutrition
subjects affected / exposed	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Hypophosphataemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 13 (0.00%)	2 / 30 (6.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 14 (7.14%)	0 / 2 (0.00%)	1 / 16 (6.25%)	1 / 16 (6.25%)	0 / 19 (0.00%)
occurrences all number	1	0	0	0	0	0	0	3	0	0	0	0	0	1	0	1	1	0
Hypocalcaemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 13 (0.00%)	0 / 2 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 13 (7.69%)	0 / 30 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 14 (0.00%)	0 / 2 (0.00%)	0 / 16 (0.00%)	0 / 16 (0.00%)	2 / 19 (10.53%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	2

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Were there any global substantial amendments to the protocol? Yes

23 Mar 2020

Added a weekly LV dosing schedule for all cohorts (tumor types) (Part B [q1wk dosing]). The existing dosing schedule for LV every 3 weeks is defined as Part A (q3wk dosing). Wording throughout the protocol was revised to reflect Part A and Part B as appropriate. Added clarifying language regarding timing of safety assessments. The assessment of safety during the course of this study will consist of the surveillance and recording of AEs including SAEs, recording of concomitant medication, and measurements of protocol-specified physical examination findings, vital signs, pregnancy testing, and laboratory tests. Safety assessments will be performed at prespecified time points through the EOT visit and in some circumstances beyond the EOT visit. AEs and SAEs will be reported through the EOT visit or 30 days after the last study treatment, whichever is later.

27 Aug 2020

Added tumor types: Cohort 7: castration-resistant prostate cancer and Cohort 8: melanoma. Wording throughout the protocol was revised to reflect the addition of Cohort 7 and Cohort 8 as appropriate. Added section “Safety data of LV q1wk”. Added tumor assessment for prostate cancer participants. Updated rationale for selection of q1wk LV doses.

12 Oct 2020

Revised wording added: Withhold until toxicity resolves to <= Grade 2 or baseline, then reduce dose to the next lower dose level if treatment is resumed. If the dose is held >48 hours, the dose may be omitted, and dosing may resume on the next scheduled dosing day. If Grade 4 neutropenia recurs, reduce dose to the next lower dose level if treatment is resumed, or discontinue at the discretion of the investigator. Revised wording added: The sponsor will report all SAEs, including SUSARs, to regulatory authorities as required per local legislation or regulatory reporting requirements. Revised wording added: Results of all clinical laboratory tests except pregnancy and PSA tests are to be submitted to iRIS.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part A: Confirmed Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

Primary: Part A: Confirmed Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

Primary: Part B: Confirmed ORR as Determined by Investigator According to RECIST v1.1

Primary: Part B: Confirmed ORR as Determined by Investigator According to RECIST v1.1

Primary: Part B: Confirmed Prostate-Specific Antigen (PSA) Response Rate as Determined by Investigator According to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria, for Prostate Cancer

Primary: Part B: Confirmed Prostate-Specific Antigen (PSA) Response Rate as Determined by Investigator According to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria, for Prostate Cancer

Secondary: Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Related TEAEs and >= Grade 3 TEAE

Secondary: Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Related TEAEs and >= Grade 3 TEAE

Secondary: Part B: Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >= Grade 3 TEAE

Secondary: Part B: Number of Participants With TEAEs, TESAEs, Treatment Related TEAEs and >= Grade 3 TEAE

Secondary: Part A: Confirmed Investigator Determined Disease Control Rate (DCR) According to RECIST v1.1

Secondary: Part A: Confirmed Investigator Determined Disease Control Rate (DCR) According to RECIST v1.1

Secondary: Part B: Confirmed Investigator Determined DCR According to RECIST v1.1

Secondary: Part B: Confirmed Investigator Determined DCR According to RECIST v1.1

Secondary: Part A: Confirmed Investigator Determined Duration of Response (DOR) According to RECIST v1.1

Secondary: Part A: Confirmed Investigator Determined Duration of Response (DOR) According to RECIST v1.1

Secondary: Part B: Confirmed Investigator Determined DOR According to RECIST v1.1

Secondary: Part B: Confirmed Investigator Determined DOR According to RECIST v1.1

Secondary: Part B: Confirmed Investigator Determined PSA-DOR, for Prostate Cancer

Secondary: Part B: Confirmed Investigator Determined PSA-DOR, for Prostate Cancer

Secondary: Part A: Confirmed Investigator Determined Progression Free Survival (PFS) According to RECIST v1.1

Secondary: Part A: Confirmed Investigator Determined Progression Free Survival (PFS) According to RECIST v1.1

Secondary: Part B: Confirmed Investigator Determined PFS According to RECIST v1.1

Secondary: Part B: Confirmed Investigator Determined PFS According to RECIST v1.1

Secondary: Part B: Confirmed Investigator Determined PSA-PFS, for Prostate Cancer

Secondary: Part B: Confirmed Investigator Determined PSA-PFS, for Prostate Cancer

Secondary: Part A: Overall Survival (OS)

Secondary: Part A: Overall Survival (OS)

Secondary: Part B: Overall Survival

Secondary: Part B: Overall Survival

Secondary: Part A: Maximum Serum Concentration (Cmax) According to Antibody-Drug Conjugate (ADC) Pharmacokinetic Parameters

Secondary: Part A: Maximum Serum Concentration (Cmax) According to Antibody-Drug Conjugate (ADC) Pharmacokinetic Parameters

Secondary: Part A: Area Under the Serum Concentration Time Curve Between Days 0 to 21 (AUC21) of Ladiratuzumab Vedotin

Secondary: Part A: Area Under the Serum Concentration Time Curve Between Days 0 to 21 (AUC21) of Ladiratuzumab Vedotin

Secondary: Part A: AUC21 of Total Antibody (TAB)

Secondary: Part A: AUC21 of Total Antibody (TAB)

Secondary: Part A: Cmax According to TAB Pharmacokinetic Parameters

Secondary: Part A: Cmax According to TAB Pharmacokinetic Parameters

Secondary: Part A: Cmax According to MMAE Pharmacokinetic Parameters

Secondary: Part A: Cmax According to MMAE Pharmacokinetic Parameters

Secondary: Part A: AUC21 of Monomethyl Auristatin E (MMAE)

Secondary: Part A: AUC21 of Monomethyl Auristatin E (MMAE)

Secondary: Part B: Area Under the Concentration Time Curve Between Day 0 to 7 (AUC7) of ADC

Secondary: Part B: Area Under the Concentration Time Curve Between Day 0 to 7 (AUC7) of ADC

Secondary: Part B: Cmax According to ADC Pharmacokinetic Parameters

Secondary: Part B: Cmax According to ADC Pharmacokinetic Parameters

Secondary: Part B: AUC7 of TAB

Secondary: Part B: AUC7 of TAB

Secondary: Part B: Cmax According to TAB Pharmacokinetic Parameters

Secondary: Part B: Cmax According to TAB Pharmacokinetic Parameters

Secondary: Part B: AUC7 OF MMAE

Secondary: Part B: AUC7 OF MMAE

Secondary: Part B: Cmax According to MMAE Pharmacokinetic Parameters

Secondary: Part B: Cmax According to MMAE Pharmacokinetic Parameters

Secondary: Part A: Number of Participants With Positive Post-Baseline Antitherapeutic Antibody (ATA) Incidence

Secondary: Part A: Number of Participants With Positive Post-Baseline Antitherapeutic Antibody (ATA) Incidence

Secondary: Part B: Number of Participants With Positive Post-Baseline ATA Incidence

Secondary: Part B: Number of Participants With Positive Post-Baseline ATA Incidence

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors