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Clinical Trial Results:
A phase I/II, open-label, multi-center study of the safety and efficacy of BLZ945 as single agent and in combination with PDR001 in adults patients with advanced solid tumors

Summary
EudraCT number	2015-005806-12
Trial protocol	ES
Global end of trial date	01 Dec 2022

Results information
Results version number	v2(current)
This version publication date	03 Feb 2024
First version publication date	01 Dec 2023
Other versions	v1
Version creation reason	New data added to full data set To add in one endpoint two reporting groups that were accidentally missed

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

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Trial information

Top of page

Sponsor protocol code

CBLZ945X2101

ISRCTN number

US NCT number

NCT02829723

WHO universal trial number (UTN)

Sponsor organisation name

Novartis

Sponsor organisation address

Novartis Campus, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis, 41 613241111, Novartis.email@novartis.com

Scientific contact

Clinical Disclosure Office, Novartis, 41 613241111, Novartis.email@novartis.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

01 Dec 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

01 Dec 2022

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objectives of the trial were: • Phase I: To characterize the safety and tolerability and to estimate the maximum tolerated doses (MTDs) and/or recommended phase 2 doses (RP2Ds) of BLZ945 as a single agent (in non- Japanese and Japanese patients, separately) and in combination with PDR001. • Phase II: To assess the anti-tumor activity of BLZ945 in combination with PDR001 (and BLZ945 as single agent if appropriate)

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Oct 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Israel: 13

Country: Number of subjects enrolled

Italy: 31

Country: Number of subjects enrolled

Japan: 8

Country: Number of subjects enrolled

Singapore: 13

Country: Number of subjects enrolled

Spain: 49

Country: Number of subjects enrolled

Switzerland: 1

Country: Number of subjects enrolled

Taiwan: 25

Country: Number of subjects enrolled

United States: 52

Worldwide total number of subjects

192

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)

138

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Participants took part in 14 investigative sites in 8 countries.

Screening details

The screening period began once patients had signed the study informed consent. Screening evaluations were performed within 28 days prior to the first dose of study medication. After screening, the treatment period started on Cycle 1 Day 1.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Phase I: BLZ945 150 mg 7d on/7d off QD

Arm description

BLZ945 150 mg once per day administered for 7 days and suspended for 7 days

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 150 mg once per day administered for 7 days and suspended for 7 days

Phase I: BLZ945 300 mg 7d on/7d off QD

Arm description

BLZ945 300 mg once per day administered for 7 days and suspended for 7 days

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 300 mg once per day administered for 7 days and suspended for 7 days

Phase I: BLZ945 300 mg Q1W QD

Arm description

BLZ945 300 mg once per day once weekly

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 300 mg once per day (in the morning) once weekly

Phase I: BLZ945 450 mg Q1W QD

Arm description

BLZ945 450 mg once per day once weekly

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 450 mg once per day (in the morning) once weekly

Phase I: BLZ945 600 mg Q1W QD

Arm description

BLZ945 600 mg once per day once weekly

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 600 mg once per day (in the morning) once weekly

Phase I: BLZ945 1000 mg Q1W QD

Arm description

BLZ945 1000 mg once per day once weekly

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 1000 mg once per day (in the morning) once weekly

Phase I: BLZ945 1600 mg Q1W QD

Arm description

BLZ945 1600 mg once per day once weekly

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 1600 mg once per day (in the morning) once weekly

Phase I: BLZ945 300 mg 4d on/10d off QD

Arm description

BLZ945 300 mg once per day administered for 4 days and suspended for 10 days

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 300 mg once per day administered for 4 days and suspended for 10 days

Phase I: BLZ945 600 mg 4d on/10d off QD

Arm description

BLZ945 600 mg once per day administered for 4 days and suspended for 10 days

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 600 mg once per day administered for 4 days and suspended for 10 days

Phase I: BLZ945 800 mg 4d on/10d off QD

Arm description

BLZ945 800 mg once per day administered for 4 days and suspended for 10 days

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 800 mg once per day administered for 4 days and suspended for 10 days

Phase I: BLZ945 1200 mg 4d on/10d off QD

Arm description

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days

Phase I: BLZ945 600 mg Q1W BID

Arm description

BLZ945 600 mg twice per day once weekly

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 600 mg twice per day (in the morning and in the evening) once weekly

Phase I: BLZ945 600 mg 4d on/10d off BID

Arm description

BLZ945 600 mg twice per day administered for 4 days and suspended for 10 days

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 600 mg twice per day administered for 4 days and suspended for 10 days

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Arm description

BLZ945 150 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 150 mg once per day (in the morning) once weekly

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Arm description

BLZ945 300 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 300 mg once per day (in the morning) once weekly

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Arm description

BLZ945 600 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 600 mg once per day (in the morning) once weekly

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Arm description

BLZ945 1000 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 1000 mg once per day (in the morning) once weekly

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Arm description

BLZ945 1400 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 1400 mg once per day (in the morning) once weekly

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Arm description

BLZ945 300 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 300 mg once per day administered for 4 days and suspended for 10 days

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Arm description

BLZ945 450 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 450 mg once per day administered for 4 days and suspended for 10 days

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Arm description

BLZ945 700 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 700 mg once per day administered for 4 days and suspended for 10 days

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Arm description

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Arm description

BLZ945 600 mg twice per day once weekly in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 600 mg twice per day (in the morning and in the evening) once weekly

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Arm description

BLZ945 800 mg twice per day once weekly in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 600 mg twice per day (in the morning and in the evening) once weekly

Phase II: BLZ945 1200 mg 4d on/10d off QD

Arm description

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days

Arm type

Experimental

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days

Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Arm description

BLZ945 700 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Arm type

Experimental

Investigational medicinal product name

spartalizumab

Investigational medicinal product code

PDR001

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 400 mg administered via i.v. infusion every 4 weeks

Investigational medicinal product name

sotuletinib

Investigational medicinal product code

BLZ945

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

BLZ945 700 mg once per day administered for 4 days and suspended for 10 days

Number of subjects in period 1	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Started	5	7	5	6	3	5	6	8	9	5	10	5	6	4	5	9	5	6	5	11	9	4	6	5	22	21
Safety Set	5	7	5	6	3	5	6	8	9	5	10	4	6	4	5	9	5	6	5	11	9	4	6	5	22	21
Japanese cohort	0	0	0	0	0	0	0	3	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	5	7	5	6	3	5	6	8	9	5	10	5	6	4	5	9	5	6	5	11	9	4	6	5	22	21
Physician decision	-	-	-	-	-	-	-	-	-	1	1	-	1	-	-	2	-	-	-	-	-	1	1	1	1	3
Adverse Event	-	-	1	1	-	-	-	1	-	-	-	-	-	1	1	1	2	1	1	3	-	-	1	1	3	5
Death	1	-	1	1	-	-	2	-	1	-	-	2	1	-	-	-	-	-	-	-	2	-	-	-	1	2
Study terminated by sponsor	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-
Progressive disease	4	6	3	3	3	5	4	6	8	4	9	3	4	2	4	5	3	4	4	7	6	3	3	3	16	10
Subject/guardian decision	-	1	-	1	-	-	-	1	-	-	-	-	-	1	-	1	-	1	-	1	-	-	1	-	1	1

Baseline characteristics

Top of page

Reporting group title

Phase I: BLZ945 150 mg 7d on/7d off QD

Reporting group description

BLZ945 150 mg once per day administered for 7 days and suspended for 7 days

Reporting group title

Phase I: BLZ945 300 mg 7d on/7d off QD

Reporting group description

BLZ945 300 mg once per day administered for 7 days and suspended for 7 days

Reporting group title

Phase I: BLZ945 300 mg Q1W QD

Reporting group description

BLZ945 300 mg once per day once weekly

Reporting group title

Phase I: BLZ945 450 mg Q1W QD

Reporting group description

BLZ945 450 mg once per day once weekly

Reporting group title

Phase I: BLZ945 600 mg Q1W QD

Reporting group description

BLZ945 600 mg once per day once weekly

Reporting group title

Phase I: BLZ945 1000 mg Q1W QD

Reporting group description

BLZ945 1000 mg once per day once weekly

Reporting group title

Phase I: BLZ945 1600 mg Q1W QD

Reporting group description

BLZ945 1600 mg once per day once weekly

Reporting group title

Phase I: BLZ945 300 mg 4d on/10d off QD

Reporting group description

BLZ945 300 mg once per day administered for 4 days and suspended for 10 days

Reporting group title

Phase I: BLZ945 600 mg 4d on/10d off QD

Reporting group description

BLZ945 600 mg once per day administered for 4 days and suspended for 10 days

Reporting group title

Phase I: BLZ945 800 mg 4d on/10d off QD

Reporting group description

BLZ945 800 mg once per day administered for 4 days and suspended for 10 days

Reporting group title

Phase I: BLZ945 1200 mg 4d on/10d off QD

Reporting group description

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days

Reporting group title

Phase I: BLZ945 600 mg Q1W BID

Reporting group description

BLZ945 600 mg twice per day once weekly

Reporting group title

Phase I: BLZ945 600 mg 4d on/10d off BID

Reporting group description

BLZ945 600 mg twice per day administered for 4 days and suspended for 10 days

Reporting group title

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 150 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 300 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 600 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 1000 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 1400 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 300 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 450 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 700 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Reporting group description

BLZ945 600 mg twice per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Reporting group description

BLZ945 800 mg twice per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase II: BLZ945 1200 mg 4d on/10d off QD

Reporting group description

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days

Reporting group title

Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 700 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Reporting group values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Total
Number of subjects	5	7	5	6	3	5	6	8	9	5	10	5	6	4	5	9	5	6	5	11	9	4	6	5	22	21	192
Age Categorical
Units: participants
18 - < 65 years	5	5	4	5	3	3	3	6	6	4	5	4	3	2	5	9	3	5	3	6	7	3	1	4	15	19	138
65 - < 85 years	0	2	1	1	0	2	3	2	3	1	5	1	3	2	0	0	2	1	2	5	2	1	5	1	7	2	54
Age Continuous
Units: years
arithmetic mean (standard deviation)	50.8 ( 9.42 )	55.0 ( 17.68 )	59.2 ( 13.33 )	55.3 ( 9.40 )	59.0 ( 3.61 )	55.4 ( 18.85 )	60.7 ( 14.24 )	55.5 ( 15.11 )	54.6 ( 17.48 )	57.6 ( 6.95 )	63.0 ( 8.94 )	52.8 ( 15.64 )	57.0 ( 16.80 )	53.5 ( 18.77 )	59.6 ( 3.21 )	46.7 ( 9.11 )	58.2 ( 13.52 )	50.7 ( 16.68 )	49.8 ( 19.77 )	58.9 ( 13.26 )	50.6 ( 15.42 )	46.3 ( 15.59 )	67.2 ( 9.37 )	53.2 ( 13.31 )	56.8 ( 12.64 )	55.0 ( 8.79 )	-
Sex: Female, Male
Units: participants
Female	2	3	3	3	0	4	3	4	5	3	5	0	2	3	2	4	1	2	2	4	2	2	3	3	8	6	79
Male	3	4	2	3	3	1	3	4	4	2	5	5	4	1	3	5	4	4	3	7	7	2	3	2	14	15	113
Race/Ethnicity, Customized
Units: Subjects
Asian	1	5	1	1	2	0	1	3	6	1	2	0	2	1	1	4	0	3	2	3	2	2	3	1	1	1	49
Black or African American	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2	1	0	0	0	0	0	7
White	4	2	4	2	1	5	5	5	3	4	7	4	4	3	4	4	5	3	3	6	6	2	3	4	20	20	133
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Other	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2

End points

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Reporting group title

Phase I: BLZ945 150 mg 7d on/7d off QD

Reporting group description

BLZ945 150 mg once per day administered for 7 days and suspended for 7 days

Reporting group title

Phase I: BLZ945 300 mg 7d on/7d off QD

Reporting group description

BLZ945 300 mg once per day administered for 7 days and suspended for 7 days

Reporting group title

Phase I: BLZ945 300 mg Q1W QD

Reporting group description

BLZ945 300 mg once per day once weekly

Reporting group title

Phase I: BLZ945 450 mg Q1W QD

Reporting group description

BLZ945 450 mg once per day once weekly

Reporting group title

Phase I: BLZ945 600 mg Q1W QD

Reporting group description

BLZ945 600 mg once per day once weekly

Reporting group title

Phase I: BLZ945 1000 mg Q1W QD

Reporting group description

BLZ945 1000 mg once per day once weekly

Reporting group title

Phase I: BLZ945 1600 mg Q1W QD

Reporting group description

BLZ945 1600 mg once per day once weekly

Reporting group title

Phase I: BLZ945 300 mg 4d on/10d off QD

Reporting group description

BLZ945 300 mg once per day administered for 4 days and suspended for 10 days

Reporting group title

Phase I: BLZ945 600 mg 4d on/10d off QD

Reporting group description

BLZ945 600 mg once per day administered for 4 days and suspended for 10 days

Reporting group title

Phase I: BLZ945 800 mg 4d on/10d off QD

Reporting group description

BLZ945 800 mg once per day administered for 4 days and suspended for 10 days

Reporting group title

Phase I: BLZ945 1200 mg 4d on/10d off QD

Reporting group description

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days

Reporting group title

Phase I: BLZ945 600 mg Q1W BID

Reporting group description

BLZ945 600 mg twice per day once weekly

Reporting group title

Phase I: BLZ945 600 mg 4d on/10d off BID

Reporting group description

BLZ945 600 mg twice per day administered for 4 days and suspended for 10 days

Reporting group title

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 150 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 300 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 600 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 1000 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 1400 mg once per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 300 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 450 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 700 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Reporting group description

BLZ945 600 mg twice per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Reporting group description

BLZ945 800 mg twice per day once weekly in combination with PDR001 400 mg every 4 weeks

Reporting group title

Phase II: BLZ945 1200 mg 4d on/10d off QD

Reporting group description

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days

Reporting group title

Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 700 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks

Subject analysis set title

Phase I-II: BLZ945 1200 mg 4d on/10d off QD

Subject analysis set type

Full analysis

Subject analysis set description

BLZ945 1200 mg once per day administered for 4 days and suspended for 10 days. Patients from phase I and II treated at the same dose level and regimen pooled.

Subject analysis set title

Phase I-II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Subject analysis set type

Full analysis

Subject analysis set description

BLZ945 700 mg once per day administered for 4 days and suspended for 10 days in combination with PDR001 400 mg every 4 weeks. Patients from phase I and II treated at the same dose level and regimen pooled.

Subject analysis set title

Phase I: BLZ945 300 mg Q1W BID

Subject analysis set type

Safety analysis

Subject analysis set description

Patients assigned to BLZ945 600 mg Q1W BID who actually received BLZ945 300 mg Q1W BID

Primary: Phase I: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the on-treatment period

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End point title

Phase I: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the on-treatment period ^[1] ^[2]

End point description

Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.

End point type

Primary

End point timeframe

From first dose of study medication up to 30 days after last dose, with a maximum duration of 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis were planned for this endpoint
[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 only applies to Phase I

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W BID
Number of subjects analysed	5	7	5	6	3	5	6	8	9	5	10	4	6	4	5	9	5	6	5	11	9	4	6	5	1
Units: participants
AEs	5	7	5	6	3	5	6	8	9	5	10	4	6	4	5	9	5	6	5	11	9	4	6	5	1
Treatment-related AEs	3	7	5	4	3	5	5	6	8	4	7	4	6	2	4	7	5	4	4	8	4	4	5	4	0
SAEs	3	1	3	2	0	3	3	4	3	3	5	3	5	1	1	5	4	3	1	5	7	4	2	1	0
Treatment-related SAEs	0	0	0	1	0	0	0	1	2	0	0	0	0	0	0	2	0	0	0	1	1	3	0	1	0
Fatal SAEs	1	0	0	1	0	0	1	0	1	0	0	2	0	0	0	0	0	0	0	0	2	0	1	0	0

No statistical analyses for this end point

Primary: Phase I: Number of participants with dose reductions and dose interruptions of BLZ945

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End point title

Phase I: Number of participants with dose reductions and dose interruptions of BLZ945 ^[3] ^[4]

End point description

Number of participants with at least one dose reduction of BLZ945 and number of participants with at least one dose interruption of BLZ945.

End point type

Primary

End point timeframe

From first dose of study medication up to last dose, with a maximum duration of 3 years for BLZ945 single agent and 4 years for BLZ945 in combination with PDR001

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis were planned for this endpoint
[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 only applies to Phase I

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W BID
Number of subjects analysed	5	7	5	6	3	5	6	8	9	5	10	4	6	4	5	9	5	6	5	11	9	4	6	5	1
Units: participants
At least one dose reduction	0	2	0	0	1	0	0	0	0	0	1	1	2	0	0	0	1	1	0	1	0	0	1	2	0
At least one dose interruption	4	2	2	3	1	3	1	2	0	2	5	1	1	0	1	4	2	3	1	4	6	2	2	1	0

No statistical analyses for this end point

Primary: Phase I: Number of participants with dose reductions and dose interruptions of PDR001

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End point title

Phase I: Number of participants with dose reductions and dose interruptions of PDR001 ^[5] ^[6]

End point description

Number of participants with at least one dose reduction of PDR001 and number of participants with at least one dose interruption of PDR001. Dose reductions were not permitted for PDR001.

End point type

Primary

End point timeframe

From first dose of study medication up to last dose, with a maximum duration of 4 years

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: No statistical analysis were planned for this endpoint
[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 only applies to BLZ945+PDR001 combination group

End point values	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W
Number of subjects analysed	4	5	9	5	6	5	11	9	4	6	5
Units: participants
At least one dose reduction	0	0	0	0	0	0	0	0	0	0	0
At least one dose interruption	0	0	1	0	0	0	3	2	0	1	1

No statistical analyses for this end point

Primary: Phase I: Dose intensity of BLZ945

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End point title

Phase I: Dose intensity of BLZ945 ^[7] ^[8]

End point description

Dose intensity of BLZ945 was calculated as cumulative actual dose in milligrams divided by the number of dose days scheduled per protocol during the treatment period. The denominator was calculated considering that patients received doses 7 days out of every 14 in the 7 days on/7 days off regimen, 4 days out of every 14 in the 4 days on/10 days off regimen and 1 day out of every 7 in the Q1W regimen. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.

End point type

Primary

End point timeframe

From first dose of study medication up to last dose, with a maximum duration of 3 years for BLZ945 single agent and 4 years for BLZ945 in combination with PDR001

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis were planned for this endpoint
[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 only applies to Phase I

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W BID
Number of subjects analysed	5	7	5	6	3	5	6	8	9	5	10	4	6	4	5	9	5	6	5	11	9	4	6	5	1
Units: mg/day
arithmetic mean (standard deviation)	141.4 ( 5.16 )	250.1 ( 39.30 )	281.8 ( 52.50 )	399.2 ( 63.71 )	525.0 ( 129.90 )	959.5 ( 132.40 )	1570.9 ( 153.93 )	277.8 ( 25.70 )	578.8 ( 27.27 )	705.1 ( 98.99 )	1055.0 ( 103.62 )	1063.1 ( 321.62 )	1105.5 ( 71.77 )	160.0 ( 14.14 )	293.5 ( 14.50 )	566.3 ( 51.79 )	945.7 ( 87.13 )	1259.0 ( 209.04 )	286.0 ( 18.49 )	416.1 ( 32.30 )	606.9 ( 56.03 )	862.0 ( 243.73 )	1125.1 ( 224.13 )	1448.0 ( 386.16 )	600.0 ( 999 )

No statistical analyses for this end point

Primary: Phase I: Dose intensity of PDR001

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End point title

Phase I: Dose intensity of PDR001 ^[9] ^[10]

End point description

Dose intensity of PDR001 was calculated as cumulative actual dose in milligrams divided by the number of dose days scheduled per protocol during the treatment period. The denominator was calculated considering that patients received doses 1 day out of every 28 in the Q4W regimen.

End point type

Primary

End point timeframe

From first dose of study medication up to last dose, with a maximum duration of 4 years

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis were planned for this endpoint
[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 only applies to BLZ945+PDR001 combination group

End point values	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W
Number of subjects analysed	4	5	9	5	6	5	11	9	4	6	5
Units: mg/day
arithmetic mean (standard deviation)	533.3 ( 188.56 )	400.0 ( 0.00 )	400.0 ( 0.00 )	426.7 ( 59.63 )	433.3 ( 81.65 )	420.0 ( 44.72 )	390.5 ( 31.46 )	393.1 ( 14.05 )	400.0 ( 0.00 )	466.7 ( 163.30 )	453.3 ( 202.21 )

No statistical analyses for this end point

Primary: Phase I: Number of participants with Dose-Limiting Toxicities (DLTs) (non-Japanese cohort)

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End point title

Phase I: Number of participants with Dose-Limiting Toxicities (DLTs) (non-Japanese cohort) ^[11] ^[12]

End point description

A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 28 days of treatment with BLZ945 as single agent or in combination with PDR001 during the dose escalation part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

End point type

Primary

End point timeframe

28 days

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis were planned for this endpoint
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint only applies to Phase I non-Japanese cohort

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W BID
Number of subjects analysed	5	7	5	6	3	5	6	5	4	4	9	4	6	4	5	9	5	6	5	11	8	3	6	4	0 ^[13]
Units: participants	0	2	0	1	0	0	1	0	0	0	1	1	1	0	0	0	0	0	1	1	1	2	0	2

Notes
[13] - No patients met the minimum exposure criteria to be included in this analysis set

No statistical analyses for this end point

Primary: Phase I: Number of participants with Dose-Limiting Toxicities (DLTs) (Japanese cohort)

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End point title

Phase I: Number of participants with Dose-Limiting Toxicities (DLTs) (Japanese cohort) ^[14] ^[15]

End point description

End point type

Primary

End point timeframe

28 days

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

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 300 mg Q1W BID

Number of subjects analysed

0 ^[16]

0 ^[17]

0 ^[18]

0 ^[19]

0 ^[20]

0 ^[21]

0 ^[22]

0 ^[23]

0 ^[24]

0 ^[25]

0 ^[26]

0 ^[27]

Units: participants

Notes
[16] - No patients in the Japanese cohort
[17] - No patients in the Japanese cohort
[18] - No patients in the Japanese cohort
[19] - No patients in the Japanese cohort
[20] - No patients in the Japanese cohort
[21] - No patients in the Japanese cohort
[22] - No patients in the Japanese cohort
[23] - No patients in the Japanese cohort
[24] - No patients in the Japanese cohort
[25] - No patients in the Japanese cohort
[26] - No patients in the Japanese cohort
[27] - No patients in the Japanese cohort

No statistical analyses for this end point

Primary: Phase II: Progression-Free Survival rate at 6 months (PFS6) per RANO criteria for glioblastoma

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End point title

Phase II: Progression-Free Survival rate at 6 months (PFS6) per RANO criteria for glioblastoma ^[28] ^[29]

End point description

PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment per Response Assessment in Neuro Oncology (RANO) criteria. PFS was analyzed using Kaplan-Meier estimates.

End point type

Primary

End point timeframe

6 months

Notes
[28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis were planned for this endpoint
[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 only applies to Phase II

End point values	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	22	21
Units: percentage of participants
number (confidence interval 95%)	15.2 (3.8 to 33.9)	22.2 (7.1 to 42.6)

No statistical analyses for this end point

Secondary: Phase I: Progression-Free Survival (PFS) per RECIST v1.1

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End point title

Phase I: Progression-Free Survival (PFS) per RECIST v1.1 ^[30]

End point description

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. PFS was analyzed using Kaplan-Meier estimates. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not available’). Therefore, not available values because of insufficient number of participants with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until first documented progression or death due to any cause, assessed up to 3.1 years for BLZ945 single agent and 4.4 years for BLZ945 in combination with PDR001

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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

Units: months

median (confidence interval 95%)

999 (1.6 to 999)

999 (999 to 999)

999 (1.7 to 999)

999 (999 to 999)

999 (1.7 to 999)

999 (999 to 999)

1.9 (1.8 to 999)

999 (1.8 to 999)

999 (999 to 999)

7.9 (1.9 to 999)

999 (999 to 999)

999 (1.9 to 999)

3.5 (-999 to 999)

999 (999 to 999)

999 (1.1 to 999)

999 (1.8 to 999)

40.1 (-999 to 999)

999 (0.0 to 999)

999 (1.8 to 999)

No statistical analyses for this end point

Secondary: Phase I: Progression-Free Survival (PFS) per irRC

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End point title

Phase I: Progression-Free Survival (PFS) per irRC ^[31]

End point description

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per immune-related Response Criteria (irRC). PFS was analyzed using Kaplan-Meier estimates. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not available’). Therefore, not available values because of insufficient number of participants with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until first documented progression or death due to any cause, assessed up to 3.1 years for BLZ945 single agent and 4.4 years for BLZ945 in combination with PDR001

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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

Units: months

median (confidence interval 95%)

999 (1.6 to 999)

999 (999 to 999)

999 (1.7 to 999)

999 (999 to 999)

999 (1.7 to 999)

999 (999 to 999)

1.9 (1.8 to 999)

999 (1.8 to 999)

999 (999 to 999)

7.9 (1.9 to 999)

999 (999 to 999)

999 (1.9 to 999)

3.5 (-999 to 999)

999 (999 to 999)

999 (1.1 to 999)

999 (1.8 to 999)

40.1 (-999 to 999)

999 (0.0 to 999)

2.6 (0.0 to 999)

999 (1.8 to 999)

No statistical analyses for this end point

Secondary: Phase I: Progression-Free Survival (PFS) per RANO

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End point title

Phase I: Progression-Free Survival (PFS) per RANO ^[32]

End point description

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per response assessment in neuro-oncology (RANO) criteria. PFS was analyzed using Kaplan-Meier estimates. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not available’). Therefore, not available values because of insufficient number of participants with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until first documented progression or death due to any cause, assessed up to 3.1 years for BLZ945 single agent and 4.4 years for BLZ945 in combination with PDR001

Notes
[32] - 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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[33]

0 ^[34]

0 ^[35]

0 ^[36]

0 ^[37]

0 ^[38]

0 ^[39]

0 ^[40]

3 ^[41]

0 ^[42]

0 ^[43]

0 ^[44]

0 ^[45]

0 ^[46]

Units: months

median (confidence interval 95%)

( to )

1.9 (-999 to 999)

( to )

0.2 (-999 to 999)

( to )

1.9 (1.3 to 999)

2.8 (0.2 to 999)

1.9 (1.9 to 999)

( to )

1.9 (-999 to 999)

3.6 (-999 to 999)

1.9 (1.4 to 999)

0.7 (0.5 to 999)

0.8 (-999 to 999)

( to )

1.1 (0.3 to 999)

Notes
[33] - No patients with glioblastoma
[34] - No patients with glioblastoma
[35] - No patients with glioblastoma
[36] - No patients with glioblastoma
[37] - No patients with glioblastoma
[38] - No patients with glioblastoma
[39] - No patients with glioblastoma
[40] - No patients with glioblastoma
[41] - No patients with glioblastoma
[42] - No patients with glioblastoma
[43] - No patients with glioblastoma
[44] - No patients with glioblastoma
[45] - No patients with glioblastoma
[46] - No patients with glioblastoma

No statistical analyses for this end point

Secondary: Phase I and II: Progression-Free Survival (PFS) per iRANO

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End point title

Phase I and II: Progression-Free Survival (PFS) per iRANO

End point description

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per immune response assessment in neuro-oncology (iRANO) criteria. PFS was analyzed using Kaplan-Meier estimates. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not available’). Therefore, not available values because of insufficient number of participants with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until first documented progression or death due to any cause, assessed up to 3.1 years for BLZ945 single agent and 4.4 years for BLZ945 in combination with PDR001

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Phase II: BLZ945 1200 mg 4d on/10d off QD

Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[47]

0 ^[48]

0 ^[49]

0 ^[50]

0 ^[51]

0 ^[52]

0 ^[53]

0 ^[54]

3 ^[55]

0 ^[56]

0 ^[57]

0 ^[58]

0 ^[59]

0 ^[60]

Units: months

median (confidence interval 95%)

( to )

999 (999 to 999)

( to )

999 (999 to 999)

( to )

999 (999 to 999)

999 (1.6 to 999)

999 (999 to 999)

( to )

2.2 (-999 to 999)

999 (999 to 999)

12.0 (3.6 to 999)

1.2 (0.5 to 999)

999 (999 to 999)

( to )

3.2 (-999 to 999)

6.7 (1.1 to 999)

3.0 (1.3 to 999)

Notes
[47] - No patients with glioblastoma
[48] - No patients with glioblastoma
[49] - No patients with glioblastoma
[50] - No patients with glioblastoma
[51] - No patients with glioblastoma
[52] - No patients with glioblastoma
[53] - No patients with glioblastoma
[54] - No patients with glioblastoma
[55] - No patients with glioblastoma
[56] - No patients with glioblastoma
[57] - No patients with glioblastoma
[58] - No patients with glioblastoma
[59] - No patients with glioblastoma
[60] - No patients with glioblastoma

No statistical analyses for this end point

Secondary: Phase I: Progression-Free Survival (PFS) per guidelines for efficacy evaluation in lymphoma studies

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End point title

Phase I: Progression-Free Survival (PFS) per guidelines for efficacy evaluation in lymphoma studies ^[61]

End point description

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per guidelines for efficacy evaluation in lymphoma studies. PFS was analyzed using Kaplan-Meier estimates. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not available’). Therefore, not available values because of insufficient number of participants with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until first documented progression or death due to any cause, assessed up to 3.1 years for BLZ945 single agent and 4.4 years for BLZ945 in combination with PDR001

Notes
[61] - 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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[62]

0 ^[63]

0 ^[64]

0 ^[65]

0 ^[66]

0 ^[67]

0 ^[68]

0 ^[69]

0 ^[70]

0 ^[71]

0 ^[72]

0 ^[73]

0 ^[74]

0 ^[75]

0 ^[76]

0 ^[77]

0 ^[78]

0 ^[79]

0 ^[80]

0 ^[81]

0 ^[82]

0 ^[83]

Units: months

median (confidence interval 95%)

( to )

999 (999 to 999)

( to )

2.2 (1.5 to 999)

( to )

Notes
[62] - No patients with lymphoma
[63] - No patients with lymphoma
[64] - No patients with lymphoma
[65] - No patients with lymphoma
[66] - No patients with lymphoma
[67] - No patients with lymphoma
[68] - No patients with lymphoma
[69] - No patients with lymphoma
[70] - No patients with lymphoma
[71] - No patients with lymphoma
[72] - No patients with lymphoma
[73] - No patients with lymphoma
[74] - No patients with lymphoma
[75] - No patients with lymphoma
[76] - No patients with lymphoma
[77] - No patients with lymphoma
[78] - No patients with lymphoma
[79] - No patients with lymphoma
[80] - No patients with lymphoma
[81] - No patients with lymphoma
[82] - No patients with lymphoma
[83] - No patients with lymphoma

No statistical analyses for this end point

Secondary: Phase I: Best Overall Response (BOR) with confirmation per RECIST v1.1

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End point title

Phase I: Best Overall Response (BOR) with confirmation per RECIST v1.1 ^[84]

End point description

BOR is defined as the best response recorded from the start of the study treatment until disease progression/recurrence, based on local investigator assessment per RECIST v1.1. However, any assessments taken more than 30 days after the last dose of study therapy were not included in the best overall response derivation. Complete Response (CR) and Partial response (PR) had to be confirmed by a new assessment after at least 4 weeks.

End point type

Secondary

End point timeframe

From start of treatment until disease progression, assessed up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

Notes
[84] - 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 only applies to Phase I

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W
Number of subjects analysed	5	7	5	6	3	5	5	8	8	5	7	1	3	4	5	7	5	5	4	6	4	3	6	3
Units: participants
Complete Response (CR)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Partial Response (PR)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Stable Disease (SD)	3	1	1	4	0	2	0	4	3	2	2	0	1	3	2	3	1	2	2	2	4	0	1	1
Progressive Disease (PD)	1	6	4	0	3	3	3	4	4	3	4	1	2	1	3	3	3	3	1	3	0	2	4	2
Unknown	1	0	0	2	0	0	2	0	1	0	1	0	0	0	0	0	1	0	1	1	0	1	1	0
Non-CR/Non-PD (NCRNPD)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Phase I: Best Overall Response (BOR) with confirmation per irRC

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End point title

Phase I: Best Overall Response (BOR) with confirmation per irRC ^[85]

End point description

BOR is defined as the best response recorded from the start of the study treatment until disease progression/recurrence, based on local investigator assessment per irRC. However, any assessments taken more than 30 days after the last dose of study therapy were not included in the best overall response derivation. Complete Response (CR) and Partial response (PR) had to be confirmed by a new assessment after at least 4 weeks. Additionally, for irRC, progressive disease had to be confirmed.

End point type

Secondary

End point timeframe

From start of treatment until disease progression, assessed up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

Notes
[85] - 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 only applies to Phase I

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W
Number of subjects analysed	5	7	5	6	3	5	5	8	8	5	7	1	3	4	5	7	5	5	4	6	4	3	6	3
Units: participants
Complete Response (irCR)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Partial Response (irPR)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Stable Disease (irSD)	3	1	1	4	0	2	0	4	3	2	2	0	1	3	2	3	1	2	2	2	4	0	2	1
Progressive Disease (irPD)	1	6	4	0	3	3	3	4	4	3	4	1	2	1	3	3	3	3	1	3	0	2	3	2
Unknown	1	0	0	2	0	0	2	0	1	0	1	0	0	0	0	0	1	0	1	1	0	1	1	0

No statistical analyses for this end point

Secondary: Phase I and II: Best Overall Response (BOR) (sustained) per RANO

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End point title

Phase I and II: Best Overall Response (BOR) (sustained) per RANO

End point description

BOR is defined as the best response recorded from the start of the study treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started), based on local investigator assessment per RANO criteria. However, any assessments taken more than 30 days after the last dose of study therapy were not included in the best overall response derivation. If a response recorded at one scheduled magnetic resonance imaging (MRI) did not persist at the next regular scheduled MRI, the response was recorded based on the prior scan, but was designated as a non-sustained response. If the response was sustained, i.e. still present on the subsequent MRI, it was recorded as a sustained response, lasting until the time of tumor progression. CR and PR had to be confirmed by repeat assessments performed not less than 4 weeks after the criteria for response were first met.

End point type

Secondary

End point timeframe

From start of treatment until disease progression, assessed up to 4.1 years in Phase I and 1.4 years in Phase II

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	0 ^[86]	0 ^[87]	0 ^[88]	0 ^[89]	0 ^[90]	0 ^[91]	1	0 ^[92]	1	0 ^[93]	3	4	3	0 ^[94]	0 ^[95]	0 ^[96]	0 ^[97]	1	1	5	3	1	0 ^[98]	2	22	21
Units: participants
Complete Response (CR)							0		0		0	0	0					0	0	0	0	0		0	0	0
Partial Response (PR)							0		0		1	0	0					0	0	0	0	0		0	3	0
Stable Disease (SD)							0		0		0	2	1					0	1	2	0	0		0	3	5
Progressive Disease (PD) per tumor assessment							1		0		2	0	1					1	0	3	2	1		1	10	11
Progressive Disease (PD) per clinical assessment							0		1		0	1	1					0	0	0	0	0		1	4	1
Unknown							0		0		0	1	0					0	0	0	1	0		0	2	4

Notes
[86] - No patients with glioblastoma
[87] - No patients with glioblastoma
[88] - No patients with glioblastoma
[89] - No patients with glioblastoma
[90] - No patients with glioblastoma
[91] - No patients with glioblastoma
[92] - No patients with glioblastoma
[93] - No patients with glioblastoma
[94] - No patients with glioblastoma
[95] - No patients with glioblastoma
[96] - No patients with glioblastoma
[97] - No patients with glioblastoma
[98] - No patients with glioblastoma

No statistical analyses for this end point

Secondary: Phase I and II: Best Overall Response (BOR) (sustained) per iRANO

Top of page

End point title

Phase I and II: Best Overall Response (BOR) (sustained) per iRANO

End point description

BOR is defined as the best response recorded from the start of the study treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started), based on local investigator assessment per iRANO. However, any assessments taken more than 30 days after the last dose of study therapy were not included in the best overall response derivation. If a response recorded at one scheduled magnetic resonance imaging (MRI) did not persist at the next regular scheduled MRI, the response was recorded based on the prior scan, but was designated as a non-sustained response. If the response was sustained, i.e. still present on the subsequent MRI, it was recorded as a sustained response, lasting until the time of tumor progression. CR and PR had to be confirmed by repeat assessments performed not less than 4 weeks after the criteria for response were first met. Additionally, for iRANO, progressive disease had to be confirmed.

End point type

Secondary

End point timeframe

From start of treatment until disease progression, assessed up to 4.1 years in Phase I and 1.4 years in Phase II

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	0 ^[99]	0 ^[100]	0 ^[101]	0 ^[102]	0 ^[103]	0 ^[104]	1	0 ^[105]	1	0 ^[106]	3	4	3	0 ^[107]	0 ^[108]	0 ^[109]	0 ^[110]	1	1	5	3	1	0 ^[111]	2	22	21
Units: participants
Complete Response (CR)							0		0		0	0	0					0	0	0	0	0		0	0	0
Partial Response (PR)							0		0		1	0	0					0	1	0	0	0		0	3	0
Stable Disease (SD)							0		0		0	2	1					0	0	2	0	0		0	3	5
Progressive Disease (PD) per tumor assessment							0		0		0	0	0					0	0	0	1	0		0	1	0
Progressive Disease (PD) per clinical assessment							0		0		0	0	0					0	0	0	0	0		0	0	0
Unknown							1		1		2	2	2					1	0	3	2	1		2	15	16

Notes
[99] - No patients with glioblastoma
[100] - No patients with glioblastoma
[101] - No patients with glioblastoma
[102] - No patients with glioblastoma
[103] - No patients with glioblastoma
[104] - No patients with glioblastoma
[105] - No patients with glioblastoma
[106] - No patients with glioblastoma
[107] - No patients with glioblastoma
[108] - No patients with glioblastoma
[109] - No patients with glioblastoma
[110] - No patients with glioblastoma
[111] - No patients with glioblastoma

No statistical analyses for this end point

Secondary: Phase I: Best Overall Response (BOR) per guidelines for efficacy evaluation in lymphoma studies

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End point title

Phase I: Best Overall Response (BOR) per guidelines for efficacy evaluation in lymphoma studies ^[112]

End point description

BOR is defined as the best response recorded from the start of the study treatment until disease progression/recurrence, based on local investigator assessment per guidelines for efficacy evaluation in lymphoma studies. However, any assessments taken more than 30 days after the last dose of study therapy were not included in the best overall response derivation.

End point type

Secondary

End point timeframe

From start of treatment until disease progression, assessed up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

Notes
[112] - 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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[113]

0 ^[114]

0 ^[115]

0 ^[116]

0 ^[117]

0 ^[118]

0 ^[119]

0 ^[120]

0 ^[121]

0 ^[122]

0 ^[123]

0 ^[124]

0 ^[125]

0 ^[126]

0 ^[127]

0 ^[128]

0 ^[129]

0 ^[130]

0 ^[131]

0 ^[132]

0 ^[133]

0 ^[134]

Units: participants

Complete Response (CR)

Partial response (PR)

Stable disease (SD)

Progressive Disease (PD)

Unknown

Notes
[113] - No patients with lymphoma
[114] - No patients with lymphoma
[115] - No patients with lymphoma
[116] - No patients with lymphoma
[117] - No patients with lymphoma
[118] - No patients with lymphoma
[119] - No patients with lymphoma
[120] - No patients with lymphoma
[121] - No patients with lymphoma
[122] - No patients with lymphoma
[123] - No patients with lymphoma
[124] - No patients with lymphoma
[125] - No patients with lymphoma
[126] - No patients with lymphoma
[127] - No patients with lymphoma
[128] - No patients with lymphoma
[129] - No patients with lymphoma
[130] - No patients with lymphoma
[131] - No patients with lymphoma
[132] - No patients with lymphoma
[133] - No patients with lymphoma
[134] - No patients with lymphoma

No statistical analyses for this end point

Secondary: Phase I: Overall Response Rate (ORR) per RECIST v1.1

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End point title

Phase I: Overall Response Rate (ORR) per RECIST v1.1 ^[135]

End point description

ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1.

End point type

Secondary

End point timeframe

Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

Notes
[135] - 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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

Units: percentage of participants

number (confidence interval 90%)

0 (0.0 to 45.1)

0 (0.0 to 34.8)

0 (0.0 to 45.1)

0 (0.0 to 39.3)

0 (0.0 to 63.2)

0 (0.0 to 45.1)

0 (0.0 to 31.2)

0 (0.0 to 45.1)

0 (0.0 to 34.8)

0 (0.0 to 95.0)

0 (0.0 to 63.2)

0 (0.0 to 52.7)

0 (0.0 to 45.1)

14.3 (0.7 to 52.1)

0 (0.0 to 45.1)

0 (0.0 to 52.7)

0 (0.0 to 39.3)

0 (0.0 to 52.7)

0 (0.0 to 63.2)

0 (0.0 to 39.3)

0 (0.0 to 63.2)

No statistical analyses for this end point

Secondary: Phase I: Overall Response Rate (ORR) per irRC

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End point title

Phase I: Overall Response Rate (ORR) per irRC ^[136]

End point description

ORR is the percentage of patients with a best overall response of complete response (irCR) or partial response (irPR), based on local investigator assessment per irRC.

End point type

Secondary

End point timeframe

Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

Notes
[136] - 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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

Units: percentage of participants

number (confidence interval 90%)

0 (0.0 to 45.1)

0 (0.0 to 34.8)

0 (0.0 to 45.1)

0 (0.0 to 39.3)

0 (0.0 to 63.2)

0 (0.0 to 45.1)

0 (0.0 to 31.2)

0 (0.0 to 45.1)

0 (0.0 to 34.8)

0 (0.0 to 95.0)

0 (0.0 to 63.2)

0 (0.0 to 52.7)

0 (0.0 to 45.1)

14.3 (0.7 to 52.1)

0 (0.0 to 45.1)

0 (0.0 to 52.7)

0 (0.0 to 39.3)

0 (0.0 to 52.7)

0 (0.0 to 63.2)

0 (0.0 to 39.3)

0 (0.0 to 63.2)

No statistical analyses for this end point

Secondary: Phase I: Overall Response Rate (ORR) per guidelines for efficacy evaluation in lymphoma studies

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End point title

Phase I: Overall Response Rate (ORR) per guidelines for efficacy evaluation in lymphoma studies ^[137]

End point description

ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per guidelines for efficacy evaluation in lymphoma studies.

End point type

Secondary

End point timeframe

Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

Notes
[137] - 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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[138]

0 ^[139]

0 ^[140]

0 ^[141]

0 ^[142]

0 ^[143]

0 ^[144]

0 ^[145]

0 ^[146]

0 ^[147]

0 ^[148]

0 ^[149]

0 ^[150]

0 ^[151]

0 ^[152]

0 ^[153]

0 ^[154]

0 ^[155]

0 ^[156]

0 ^[157]

0 ^[158]

0 ^[159]

Units: percentage of participants

number (confidence interval 90%)

( to )

0 (0.0 to 77.6)

( to )

50.0 (2.5 to 97.5)

( to )

Notes
[138] - No patients with lymphoma
[139] - No patients with lymphoma
[140] - No patients with lymphoma
[141] - No patients with lymphoma
[142] - No patients with lymphoma
[143] - No patients with lymphoma
[144] - No patients with lymphoma
[145] - No patients with lymphoma
[146] - No patients with lymphoma
[147] - No patients with lymphoma
[148] - No patients with lymphoma
[149] - No patients with lymphoma
[150] - No patients with lymphoma
[151] - No patients with lymphoma
[152] - No patients with lymphoma
[153] - No patients with lymphoma
[154] - No patients with lymphoma
[155] - No patients with lymphoma
[156] - No patients with lymphoma
[157] - No patients with lymphoma
[158] - No patients with lymphoma
[159] - No patients with lymphoma

No statistical analyses for this end point

Secondary: Phase I: Disease Control Rate (DCR) per RECIST v1.1

Top of page

End point title

Phase I: Disease Control Rate (DCR) per RECIST v1.1 ^[160]

End point description

DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per RECIST v1.1.

End point type

Secondary

End point timeframe

Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

Notes
[160] - 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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

Units: percentage of participants

number (confidence interval 90%)

60.0 (18.9 to 92.4)

14.3 (0.7 to 52.1)

20.0 (1.0 to 65.7)

66.7 (27.1 to 93.7)

0 (0.0 to 63.2)

40.0 (7.6 to 81.1)

0 (0.0 to 45.1)

50.0 (19.3 to 80.7)

37.5 (11.1 to 71.1)

40.0 (7.6 to 81.1)

28.6 (5.3 to 65.9)

0 (0.0 to 95.0)

33.3 (1.7 to 86.5)

75.0 (24.9 to 98.7)

40.0 (7.6 to 81.1)

57.1 (22.5 to 87.1)

20.0 (1.0 to 65.7)

40.0 (7.6 to 81.1)

50.0 (9.8 to 90.2)

33.3 (6.3 to 72.9)

100 (47.3 to 100.0)

0 (0.0 to 63.2)

16.7 (0.9 to 58.2)

33.3 (1.7 to 86.5)

No statistical analyses for this end point

Secondary: Phase I: Disease Control Rate (DCR) per irRC

Top of page

End point title

Phase I: Disease Control Rate (DCR) per irRC ^[161]

End point description

DCR is the percentage of patients with a best overall response of complete response (irCR), partial response (irPR) or stable disease (irSD), based on local investigator assessment per irRC.

End point type

Secondary

End point timeframe

Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

Notes
[161] - 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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

Units: percentage of participants

number (confidence interval 90%)

60.0 (18.9 to 92.4)

14.3 (0.7 to 52.1)

20.0 (1.0 to 65.7)

66.7 (27.1 to 93.7)

0 (0.0 to 63.2)

40.0 (7.6 to 81.1)

0 (0.0 to 45.1)

50.0 (19.3 to 80.7)

37.5 (11.1 to 71.1)

40.0 (7.6 to 81.1)

28.6 (5.3 to 65.9)

0 (0.0 to 95.0)

33.3 (1.7 to 86.5)

75.0 (24.9 to 98.7)

40.0 (7.6 to 81.1)

57.1 (22.5 to 87.1)

20.0 (1.0 to 65.7)

40.0 (7.6 to 81.1)

50.0 (9.8 to 90.2)

33.3 (6.3 to 72.9)

100 (47.3 to 100)

0 (0.0 to 63.2)

33.3 (6.3 to 72.9)

33.3 (1.7 to 86.5)

No statistical analyses for this end point

Secondary: Phase I and II: Disease Control Rate (DCR) per RANO

Top of page

End point title

Phase I and II: Disease Control Rate (DCR) per RANO

End point description

DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per RANO criteria.

End point type

Secondary

End point timeframe

Up to 4.1 years in Phase I and 1.4 years in Phase II

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Phase II: BLZ945 1200 mg 4d on/10d off QD

Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[162]

0 ^[163]

0 ^[164]

0 ^[165]

0 ^[166]

0 ^[167]

0 ^[168]

0 ^[169]

3 ^[170]

0 ^[171]

0 ^[172]

0 ^[173]

0 ^[174]

0 ^[175]

Units: percentage of participants

number (confidence interval 90%)

( to )

0 (0.0 to 95.0)

( to )

0 (0.0 to 95.0)

( to )

33.3 (1.7 to 86.5)

50.0 (9.8 to 90.2)

33.3 (1.7 to 86.5)

( to )

0 (0.0 to 95.0)

100 (5.0 to 100)

40.0 (7.6 to 81.1)

0 (0.0 to 63.2)

0 (0.0 to 95.0)

( to )

0 (0.0 to 77.6)

27.3 (12.6 to 46.9)

23.8 (9.9 to 43.7)

Notes
[162] - No patients with glioblastoma
[163] - No patients with glioblastoma
[164] - No patients with glioblastoma
[165] - No patients with glioblastoma
[166] - No patients with glioblastoma
[167] - No patients with glioblastoma
[168] - No patients with glioblastoma
[169] - No patients with glioblastoma
[170] - No patients with glioblastoma
[171] - No patients with glioblastoma
[172] - No patients with glioblastoma
[173] - No patients with glioblastoma
[174] - No patients with glioblastoma
[175] - No patients with glioblastoma

No statistical analyses for this end point

Secondary: Phase I and II: Disease Control Rate (DCR) per iRANO

Top of page

End point title

Phase I and II: Disease Control Rate (DCR) per iRANO

End point description

DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per iRANO criteria.

End point type

Secondary

End point timeframe

Up to 4.1 years in Phase I and 1.4 years in Phase II

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Phase II: BLZ945 1200 mg 4d on/10d off QD

Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[176]

0 ^[177]

0 ^[178]

0 ^[179]

0 ^[180]

0 ^[181]

0 ^[182]

0 ^[183]

0 ^[184]

0 ^[185]

0 ^[186]

0 ^[187]

0 ^[188]

Units: percentage of participants

number (confidence interval 90%)

( to )

0 (0.0 to 95.0)

( to )

0 (0.0 to 95.0)

( to )

33.3 (1.7 to 86.5)

50.0 (9.8 to 90.2)

33.3 (1.7 to 86.5)

( to )

0 (0.0 to 95.0)

100 (5.0 to 100.0)

40.0 (7.6 to 81.1)

0 (0.0 to 63.2)

0 (0.0 to 95.0)

( to )

0 (0.0 to 77.6)

27.3 (12.6 to 46.9)

23.8 (9.9 to 43.7)

Notes
[176] - No patients with glioblastoma
[177] - No patients with glioblastoma
[178] - No patients with glioblastoma
[179] - No patients with glioblastoma
[180] - No patients with glioblastoma
[181] - No patients with glioblastoma
[182] - No patients with glioblastoma
[183] - No patients with glioblastoma
[184] - No patients with glioblastoma
[185] - No patients with glioblastoma
[186] - No patients with glioblastoma
[187] - No patients with glioblastoma
[188] - No patients with glioblastoma

No statistical analyses for this end point

Secondary: Phase I: Disease Control Rate (DCR) per guidelines for efficacy evaluation in lymphoma studies

Top of page

End point title

Phase I: Disease Control Rate (DCR) per guidelines for efficacy evaluation in lymphoma studies ^[189]

End point description

DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per guidelines for efficacy evaluation in lymphoma studies.

End point type

Secondary

End point timeframe

Up to 3.1 years for BLZ945 single agent and 4.1 years for BLZ945 in combination with PDR001

Notes
[189] - 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 only applies to Phase I

Phase I: BLZ945 150 mg 7d on/7d off QD

Phase I: BLZ945 300 mg 7d on/7d off QD

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 300 mg 4d on/10d off QD

Phase I: BLZ945 600 mg 4d on/10d off QD

Phase I: BLZ945 800 mg 4d on/10d off QD

Phase I: BLZ945 1200 mg 4d on/10d off QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 600 mg 4d on/10d off BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[190]

0 ^[191]

0 ^[192]

0 ^[193]

0 ^[194]

0 ^[195]

0 ^[196]

0 ^[197]

0 ^[198]

0 ^[199]

0 ^[200]

0 ^[201]

0 ^[202]

0 ^[203]

0 ^[204]

0 ^[205]

0 ^[206]

0 ^[207]

0 ^[208]

0 ^[209]

0 ^[210]

0 ^[211]

Units: percentage of participants

number (confidence interval 90%)

( to )

0 (0.0 to 77.6)

( to )

50.0 (2.5 to 97.5)

( to )

Notes
[190] - No patients with lymphoma
[191] - No patients with lymphoma
[192] - No patients with lymphoma
[193] - No patients with lymphoma
[194] - No patients with lymphoma
[195] - No patients with lymphoma
[196] - No patients with lymphoma
[197] - No patients with lymphoma
[198] - No patients with lymphoma
[199] - No patients with lymphoma
[200] - No patients with lymphoma
[201] - No patients with lymphoma
[202] - No patients with lymphoma
[203] - No patients with lymphoma
[204] - No patients with lymphoma
[205] - No patients with lymphoma
[206] - No patients with lymphoma
[207] - No patients with lymphoma
[208] - No patients with lymphoma
[209] - No patients with lymphoma
[210] - No patients with lymphoma
[211] - No patients with lymphoma

No statistical analyses for this end point

Secondary: Phase II: Duration of Response (DOR) per RANO

Top of page

End point title

Phase II: Duration of Response (DOR) per RANO ^[212]

End point description

DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RANO. DOR is defined as the time from the date of first documented response to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not available’). Therefore, not available values because of insufficient number of participants with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

Up to 1.4 years for BLZ945 single agent and 0.6 years for BLZ945 in combination with PDR001

Notes
[212] - 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 only applies to Phase II

End point values	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	3	0 ^[213]
Units: months
median (confidence interval 95%)	7.3 (6.7 to 999)	( to )

Notes
[213] - No patients with CR or PR

No statistical analyses for this end point

Secondary: Phase II: Duration of Response (DOR) per iRANO

Top of page

End point title

Phase II: Duration of Response (DOR) per iRANO ^[214]

End point description

DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per iRANO. DOR is defined as the time from the date of first documented response to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not available’). Therefore, not available values because of insufficient number of participants with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

Up to 1.4 years for BLZ945 single agent and 0.6 years for BLZ945 in combination with PDR001

Notes
[214] - 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 only applies to Phase II

End point values	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	3	0 ^[215]
Units: months
median (confidence interval 95%)	16.2 (6.7 to 999)	( to )

Notes
[215] - No patients with CR or PR

No statistical analyses for this end point

Secondary: Phase II: Overall Survival (OS)

Top of page

End point title

Phase II: Overall Survival (OS) ^[216]

End point description

OS is defined as the time from date of start of treatment to date of death due to any cause. If a patient was not known to have died, OS time was censored at the date of last contact. OS was estimated using Kaplan-Meier estimates.

End point type

Secondary

End point timeframe

From start of treatment until death due to any cause, assessed up to 1.9 years for BLZ945 single agent and 1.3 years for BLZ945 in combination with PDR001

Notes
[216] - 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 only applies to Phase II

End point values	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	22	21
Units: months
median (confidence interval 95%)	8.4 (6.4 to 13.7)	7.0 (2.3 to 10.9)

No statistical analyses for this end point

Secondary: Phase II: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the on-treatment period

Top of page

End point title

Phase II: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the on-treatment period ^[217]

End point description

End point type

Secondary

End point timeframe

From first dose of study medication up to 30 days after last dose, with a maximum duration of 1.4 years for BLZ945 single agent and 0.6 years for BLZ945 in combination with PDR001

Notes
[217] - 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 only applies to Phase II

End point values	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	22	21
Units: participants
AEs	22	20
Treatment-related AEs	14	14
SAEs	10	10
Treatment-related SAEs	2	4
Fatal SAEs	0	1

No statistical analyses for this end point

Secondary: Phase II: Number of participants with dose reductions and dose interruptions of BLZ945

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End point title

Phase II: Number of participants with dose reductions and dose interruptions of BLZ945 ^[218]

End point description

Number of participants with at least one dose reduction of BLZ945 and number of participants with at least one dose interruption of BLZ945.

End point type

Secondary

End point timeframe

From first dose of study medication up to last dose, with a maximum duration of 1.3 years for BLZ945 single agent and 0.5 years for BLZ945 in combination with PDR001

Notes
[218] - 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 only applies to Phase II

End point values	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	22	21
Units: participants
At least one dose reduction	1	1
At least one dose interruption	7	5

No statistical analyses for this end point

Secondary: Phase II: Number of participants with dose reductions and dose interruptions of PDR001

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End point title

Phase II: Number of participants with dose reductions and dose interruptions of PDR001 ^[219]

End point description

Number of participants with at least one dose reduction of PDR001 and number of participants with at least one dose interruption of PDR001. Dose reductions were not permitted for PDR001.

End point type

Secondary

End point timeframe

From first dose of study medication up to last dose, with a maximum duration of 0.5 years

Notes
[219] - 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 only applies to Phase II

End point values	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	0 ^[220]	21
Units: participants
At least one dose reduction		0
At least one dose interruption		1

Notes
[220] - Not applicable

No statistical analyses for this end point

Secondary: Phase II: Dose intensity of BLZ945

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End point title

Phase II: Dose intensity of BLZ945 ^[221]

End point description

End point type

Secondary

End point timeframe

From first dose of study medication up to last dose, with a maximum duration of 1.3 years for BLZ945 single agent and 0.5 years for BLZ945 in combination with PDR001

Notes
[221] - 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 only applies to Phase II

End point values	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	22	21
Units: mg/day
arithmetic mean (standard deviation)	1104.7 ( 119.63 )	610.4 ( 83.00 )

No statistical analyses for this end point

Secondary: Phase II: Dose intensity of PDR001

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End point title

Phase II: Dose intensity of PDR001 ^[222]

End point description

End point type

Secondary

End point timeframe

From first dose of study medication up to last dose, with a maximum duration of 0.5 years

Notes
[222] - 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 only applies to Phase II

End point values	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	0 ^[223]	21
Units: mg/day
arithmetic mean (standard deviation)	( )	395.2 ( 21.82 )

Notes
[223] - Not applicable

No statistical analyses for this end point

Secondary: Phase I and II: Maximum observed serum concentration (Cmax) of BLZ945 (7d on/7d off regimen)

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End point title

Phase I and II: Maximum observed serum concentration (Cmax) of BLZ945 (7d on/7d off regimen) ^[224]

End point description

Pharmacokinetic (PK) parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 7 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose

Notes
[224] - 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 only applies to the following dosing schedule: BLZ945 7d on/7d off regimen

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD
Number of subjects analysed	5 ^[225]	7 ^[226]
Units: µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1)	4.48 ( 1.42 )	9.33 ( 2.8 )
Cycle 1 Day 7 (C1D7)	6.58 ( 2.07 )	13.9 ( 4.51 )

Notes
[225] - n=4 (C1D1), 5 (C1D7)
[226] - n=7 (C1D1), 5 (C1D7)

No statistical analyses for this end point

Secondary: Phase I and II: Maximum observed serum concentration (Cmax) of BLZ945 (Q1W regimen)

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End point title

Phase I and II: Maximum observed serum concentration (Cmax) of BLZ945 (Q1W regimen) ^[227]

End point description

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 8 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose (QD dosing); pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post morning dose (and pre evening dose) and 12 hours post evening dose (BID dosing)

Notes
[227] - 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 only applies to the following dosing schedule: BLZ945 Q1W regimen

End point values	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W
Number of subjects analysed	5 ^[228]	6 ^[229]	3 ^[230]	5 ^[231]	6 ^[232]	3 ^[233]	4 ^[234]	5 ^[235]	8 ^[236]	5 ^[237]	6 ^[238]	5 ^[239]	3 ^[240]
Units: µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1)	8.39 ( 1.39 )	15.4 ( 3.04 )	13 ( 3.42 )	20.1 ( 3.07 )	26.4 ( 6.42 )	15 ( 3.04 )	3.94 ( 0.847 )	9.02 ( 2.14 )	16.5 ( 2.97 )	18.9 ( 2.09 )	25.3 ( 4.84 )	15.5 ( 3.13 )	17.6 ( 3.12 )
Cycle 1 Day 8 (C1D8)	8.74 ( 1.84 )	13.2 ( 4.81 )	15.8 ( 3.18 )	27.1 ( 3.3 )	29.6 ( 7.22 )	13.6 ( 3.64 )	4.68 ( 0.731 )	9.05 ( 2.94 )	17.3 ( 2.44 )	20.6 ( 4.89 )	33.9 ( 6.92 )	16.4 ( 3.83 )	16.4 ( 3.66 )

Notes
[228] - n=5 (C1D1), 4 (C1D8)
[229] - n=5 (C1D1), 6 (C1D8)
[230] - n=3 (C1D1), 3 (C1D8)
[231] - n=3 (C1D1), 5 (C1D8)
[232] - n=5 (C1D1), 6 (C1D8)
[233] - n=3 (C1D1), 3 (C1D8)
[234] - n=4 (C1D1), 3 (C1D8)
[235] - n=5 (C1D1), 5 (C1D8)
[236] - n=8 (C1D1), 8 (C1D8)
[237] - n=5 (C1D1), 5 (C1D8)
[238] - n=6 (C1D1), 5 (C1D8)
[239] - n=5 (C1D1), 5 (C1D8)
[240] - n=3 (C1D1), 3 (C1D8)

No statistical analyses for this end point

Secondary: Phase I and II: Maximum observed serum concentration (Cmax) of BLZ945 (4d on/10d off regimen)

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End point title

Phase I and II: Maximum observed serum concentration (Cmax) of BLZ945 (4d on/10d off regimen) ^[241]

End point description

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 4 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose (QD dosing); pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post morning dose (and pre evening dose) and 12 hours post evening dose (BID dosing)

Notes
[241] - 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 only applies to the following dosing schedule: BLZ945 4d on/10d off regimen

End point values	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I-II: BLZ945 1200 mg 4d on/10d off QD	Phase I-II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	8 ^[242]	8 ^[243]	5 ^[244]	6 ^[245]	5 ^[246]	11 ^[247]	4 ^[248]	30 ^[249]	27 ^[250]
Units: µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1)	9.59 ( 2.86 )	18.2 ( 3.44 )	16.2 ( 5.15 )	16.5 ( 3.06 )	9.31 ( 3.47 )	11.8 ( 3.35 )	25 ( 5.4 )	24.5 ( 5.79 )	16.7 ( 4.45 )
Cycle 1 Day 4 (C1D4)	14.4 ( 4.4 )	28.1 ( 4.26 )	23.6 ( 6.78 )	30.5 ( 5.65 )	14.1 ( 3.29 )	19.3 ( 7.53 )	40.3 ( 11.9 )	38.2 ( 10.1 )	26 ( 8.54 )

Notes
[242] - n=8 (C1D1), 8 (C1D4)
[243] - n=8 (C1D1), 8 (C1D4)
[244] - n=4 (C1D1), 5 (C1D4)
[245] - n=6 (C1D1), 6 (C1D4)
[246] - n=5 (C1D1), 5 (C1D4)
[247] - n=11 (C1D1), 11 (C1D4)
[248] - n=4 (C1D1), 3 (C1D4)
[249] - n=30 (C1D1), 26 (C1D4)
[250] - n=27 (C1D1), 26 (C1D4)

No statistical analyses for this end point

Secondary: Phase I and II: Time to reach maximum serum concentration (Tmax) of BLZ945 (7d on/7d off regimen)

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End point title

Phase I and II: Time to reach maximum serum concentration (Tmax) of BLZ945 (7d on/7d off regimen) ^[251]

End point description

Pharmacokinetic (PK) parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 7 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose

Notes
[251] - 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 only applies to the following dosing schedule: BLZ945 7d on/7d off regimen

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD
Number of subjects analysed	5 ^[252]	7 ^[253]
Units: hours
median (full range (min-max))
Cycle 1 Day 1 (C1D1)	1.29 (0.5 to 2)	1.88 (0.5 to 6)
Cycle 1 Day 7 (C1D7)	1 (0.5 to 2)	2.03 (1.1 to 4)

Notes
[252] - n=4 (C1D1), 5 (C1D7)
[253] - n=7 (C1D1), 5 (C1D7)

No statistical analyses for this end point

Secondary: Phase I and II: Time to reach maximum serum concentration (Tmax) of BLZ945 (Q1W regimen)

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End point title

Phase I and II: Time to reach maximum serum concentration (Tmax) of BLZ945 (Q1W regimen) ^[254]

End point description

End point type

Secondary

End point timeframe

Notes
[254] - 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 only applies to the following dosing schedule: BLZ945 Q1W regimen

Phase I: BLZ945 300 mg Q1W QD

Phase I: BLZ945 450 mg Q1W QD

Phase I: BLZ945 600 mg Q1W QD

Phase I: BLZ945 1000 mg Q1W QD

Phase I: BLZ945 1600 mg Q1W QD

Phase I: BLZ945 600 mg Q1W BID

Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Number of subjects analysed

5 ^[255]

6 ^[256]

3 ^[257]

5 ^[258]

6 ^[259]

3 ^[260]

4 ^[261]

5 ^[262]

8 ^[263]

5 ^[264]

6 ^[265]

5 ^[266]

3 ^[267]

Units: hours

median (full range (min-max))

Cycle 1 Day 1 (C1D1)

2.03 (1.02 to 3.92)

1.9 (1 to 2.05)

3.83 (2 to 4)

2.07 (2.07 to 3.92)

3.82 (2 to 6.13)

2.17 (1.02 to 4.13)

1.43 (0.533 to 1.95)

1.17 (1 to 3.88)

1.78 (0.5 to 4.37)

2.1 (1.57 to 8)

2.43 (1.48 to 4)

1.88 (1.55 to 11)

1.8 (1.6 to 4.15)

Cycle 1 Day 8 (C1D8)

1.88 (0.867 to 3.92)

1.53 (0.883 to 4.23)

2 (1.92 to 2)

4.07 (1.95 to 7.35)

3 (2 to 7.05)

2.12 (1.85 to 3.95)

1.9 (1.08 to 2.13)

1.03 (0.5 to 1.95)

1.98 (0.5 to 4)

1.02 (0.5 to 2.12)

2.07 (1 to 6)

2.05 (0.883 to 4)

7.1 (2 to 10)

Notes
[255] - n=5 (C1D1), 4 (C1D8)
[256] - n=5 (C1D1), 6 (C1D8)
[257] - n=3 (C1D1), 3 (C1D8)
[258] - n=3 (C1D1), 5 (C1D8)
[259] - n=5 (C1D1), 6 (C1D8)
[260] - n=3 (C1D1), 3 (C1D8)
[261] - n=4 (C1D1), 3 (C1D8)
[262] - n=5 (C1D1), 5 (C1D8)
[263] - n=8 (C1D1), 8 (C1D8)
[264] - n=5 (C1D1), 5 (C1D8)
[265] - n=6 (C1D1), 5 (C1D8)
[266] - n=5 (C1D1), 5 (C1D8)
[267] - n=3 (C1D1), 3 (C1D8)

No statistical analyses for this end point

Secondary: Phase I and II: Time to reach maximum serum concentration (Tmax) of BLZ945 (4d on/10d off regimen)

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End point title

Phase I and II: Time to reach maximum serum concentration (Tmax) of BLZ945 (4d on/10d off regimen) ^[268]

End point description

End point type

Secondary

End point timeframe

Notes
[268] - 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 only applies to the following dosing schedule: BLZ945 4d on/10d off regimen

End point values	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I-II: BLZ945 1200 mg 4d on/10d off QD	Phase I-II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	8 ^[269]	8 ^[270]	5 ^[271]	6 ^[272]	5 ^[273]	11 ^[274]	4 ^[275]	30 ^[276]	27 ^[277]
Units: hours
median (full range (min-max))
Cycle 1 Day 1 (C1D1)	1.54 (1.03 to 2.05)	2 (0.6 to 25.4)	2.07 (1.22 to 6)	0.933 (0.567 to 3.97)	1.95 (1 to 25.6)	2 (0.5 to 5.83)	3 (1.23 to 5.12)	2.06 (0.483 to 6.2)	2 (0.5 to 24.4)
Cycle 1 Day 4 (C1D4)	1.05 (0.983 to 2.02)	2.03 (0.883 to 4.05)	4 (2.08 to 7)	1.93 (1.18 to 5.85)	2.02 (1.08 to 3.95)	1.95 (1 to 27.9)	4 (3.88 to 6.13)	2.04 (0.5 to 23.9)	1.92 (0.5 to 7)

Notes
[269] - n=8 (C1D1), 8 (C1D4)
[270] - n=8 (C1D1), 8 (C1D4)
[271] - n=4 (C1D1), 5 (C1D4)
[272] - n=6 (C1D1), 6 (C1D4)
[273] - n=5 (C1D1), 5 (C1D4)
[274] - n=11 (C1D1), 11 (C1D4)
[275] - n=4 (C1D1), 3 (C1D4)
[276] - n=30 (C1D1), 26 (C1D4)
[277] - n=27 (C1D1), 26 (C1D4)

No statistical analyses for this end point

Secondary: Phase I and II: Area under the serum concentration-time curve from time zero to 24 hours post dose (AUC0-24hr) of BLZ945 (7d on/7d off regimen)

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End point title

Phase I and II: Area under the serum concentration-time curve from time zero to 24 hours post dose (AUC0-24hr) of BLZ945 (7d on/7d off regimen) ^[278]

End point description

PK parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-24hr calculation.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 7 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose

Notes
[278] - 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 only applies to the following dosing schedule: BLZ945 7d on/7d off regimen

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD
Number of subjects analysed	5 ^[279]	6 ^[280]
Units: hr*µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1)	56.2 ( 9.43 )	125 ( 30.8 )
Cycle 1 Day 7 (C1D7)	89.8 ( 35.9 )	226 ( 72.1 )

Notes
[279] - n=4 (C1D1), 5 (C1D7)
[280] - n=6 (C1D1), 4 (C1D7)

No statistical analyses for this end point

Secondary: Phase I and II: Area under the serum concentration-time curve from time zero to 24 hours post dose (AUC0-24hr) of BLZ945 (Q1W regimen, QD dosing)

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End point title

Phase I and II: Area under the serum concentration-time curve from time zero to 24 hours post dose (AUC0-24hr) of BLZ945 (Q1W regimen, QD dosing) ^[281]

End point description

PK parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-24hr calculation.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 8 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose

Notes
[281] - 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 only applies to the following dosing schedule: BLZ945 Q1W regimen, QD dosing

End point values	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W
Number of subjects analysed	5 ^[282]	6 ^[283]	3 ^[284]	3 ^[285]	6 ^[286]	0 ^[287]	4 ^[288]	5 ^[289]	8 ^[290]	5 ^[291]	6 ^[292]	0 ^[293]	0 ^[294]
Units: hr*µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1)	118 ( 17.3 )	187 ( 43.3 )	211 ( 44.1 )	326 ( 39.9 )	399 ( 48.1 )	( )	51.6 ( 20.8 )	118 ( 27 )	218 ( 19.5 )	290 ( 20.5 )	410 ( 76 )	( )	( )
Cycle 1 Day 8 (C1D8)	136 ( 31.9 )	182 ( 71.9 )	226 ( 48.5 )	422 ( 95 )	481 ( 126 )	( )	69.4 ( 8.67 )	120 ( 27.7 )	233 ( 37.3 )	323 ( 105 )	486 ( 118 )	( )	( )

Notes
[282] - n=5 (C1D1), 3 (C1D8)
[283] - n=5 (C1D1), 6 (C1D8)
[284] - n=3 (C1D1), 3 (C1D8)
[285] - n=3 (C1D1), 3 (C1D8)
[286] - n=4 (C1D1), 6 (C1D8)
[287] - Not applicable
[288] - n=4 (C1D1), 3 (C1D8)
[289] - n=5 (C1D1), 5 (C1D8)
[290] - n=7 (C1D1), 8 (C1D8)
[291] - n=4 (C1D1), 5 (C1D8)
[292] - n=6 (C1D1), 5 (C1D8)
[293] - Not applicable
[294] - Not applicable

No statistical analyses for this end point

Secondary: Phase I and II: Area under the serum concentration-time curve from time zero to 12 hours post dose (AUC0-12hr) of BLZ945 (Q1W regimen, BID dosing)

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End point title

Phase I and II: Area under the serum concentration-time curve from time zero to 12 hours post dose (AUC0-12hr) of BLZ945 (Q1W regimen, BID dosing) ^[295]

End point description

PK parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 8 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post morning dose (and pre evening dose) and 12 hours post evening dose

Notes
[295] - 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 only applies to the following dosing schedule: BLZ945 Q1W regimen, BID dosing

End point values	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W
Number of subjects analysed	0 ^[296]	0 ^[297]	0 ^[298]	0 ^[299]	0 ^[300]	2 ^[301]	0 ^[302]	0 ^[303]	0 ^[304]	0 ^[305]	0 ^[306]	5 ^[307]	2 ^[308]
Units: hr*µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1)	( )	( )	( )	( )	( )	127 ( 38.8 )	( )	( )	( )	( )	( )	119 ( 1.69 )	159 ( 27.2 )
Cycle 1 Day 8 (C1D8)	( )	( )	( )	( )	( )	999 ( 999 )	( )	( )	( )	( )	( )	142 ( 30.4 )	165 ( 999 )

Notes
[296] - Not applicable
[297] - Not applicable
[298] - Not applicable
[299] - Not applicable
[300] - Not applicable
[301] - n=2 (C1D1), 0 (C1D8)
[302] - Not applicable
[303] - Not applicable
[304] - Not applicable
[305] - Not applicable
[306] - Not applicable
[307] - n=2 (C1D1), 5 (C1D8)
[308] - n=2 (C1D1), 1 (C1D8)

No statistical analyses for this end point

Secondary: Phase I and II: Area under the serum concentration-time curve from time zero to 24 hours post dose (AUC0-24hr) of BLZ945 (4d on/10d off regimen, QD dosing)

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End point title

Phase I and II: Area under the serum concentration-time curve from time zero to 24 hours post dose (AUC0-24hr) of BLZ945 (4d on/10d off regimen, QD dosing) ^[309]

End point description

PK parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-24hr calculation.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 4 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose

Notes
[309] - 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 only applies to the following dosing schedule: BLZ945 4d on/10d off regimen, QD dosing

End point values	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I-II: BLZ945 1200 mg 4d on/10d off QD	Phase I-II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	8 ^[310]	8 ^[311]	4 ^[312]	0 ^[313]	5 ^[314]	11 ^[315]	3 ^[316]	26 ^[317]	27 ^[318]
Units: hr*µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1)	117 ( 26.7 )	268 ( 32.2 )	241 ( 74.2 )	( )	138 ( 39.2 )	165 ( 54.1 )	424 ( 87.9 )	371 ( 88.6 )	231 ( 62.2 )
Cycle 1 Day 4 (C1D4)	212 ( 71.7 )	444 ( 88.6 )	418 ( 73.1 )	( )	197 ( 95.6 )	301 ( 124 )	656 ( 224 )	653 ( 189 )	431 ( 156 )

Notes
[310] - n=8 (C1D1), 8 (C1D4)
[311] - n=8 (C1D1), 7 (C1D4)
[312] - n=4 (C1D1), 4 (C1D4)
[313] - Not applicable
[314] - n=5 (C1D1), 4 (C1D4)
[315] - n=10 (C1D1), 11 (C1D4)
[316] - n=3 (C1D1), 2 (C1D4)
[317] - n=26 (C1D1), 20 (C1D4)
[318] - n=27 (C1D1), 21 (C1D4)

No statistical analyses for this end point

Secondary: Phase I and II: Area under the serum concentration-time curve from time zero to 12 hours post dose (AUC0-12hr) of BLZ945 (4d on/10d off regimen, BID dosing)

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End point title

Phase I and II: Area under the serum concentration-time curve from time zero to 12 hours post dose (AUC0-12hr) of BLZ945 (4d on/10d off regimen, BID dosing) ^[319]

End point description

PK parameters were calculated based on BLZ945 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 4 (1 cycle=28 days): pre-dose, 0.5, 1, 2, 4, 6, 8 and 12 hours post morning dose (and pre evening dose) and 12 hours post evening dose

Notes
[319] - 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 only applies to the following dosing schedule: BLZ945 4d on/10d off regimen, BID dosing

End point values	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I-II: BLZ945 1200 mg 4d on/10d off QD	Phase I-II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	0 ^[320]	0 ^[321]	0 ^[322]	4 ^[323]	0 ^[324]	0 ^[325]	0 ^[326]	0 ^[327]	0 ^[328]
Units: hr*µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1)	( )	( )	( )	123 ( 31.4 )	( )	( )	( )	( )	( )
Cycle 1 Day 4 (C1D4)	( )	( )	( )	235 ( 51.9 )	( )	( )	( )	( )	( )

Notes
[320] - Not applicable
[321] - Not applicable
[322] - Not applicable
[323] - n=4 (C1D1), 3 (C1D4)
[324] - Not applicable
[325] - Not applicable
[326] - Not applicable
[327] - Not applicable
[328] - Not applicable

No statistical analyses for this end point

Secondary: Phase I and II: Maximum observed serum concentration (Cmax) of PDR001

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End point title

Phase I and II: Maximum observed serum concentration (Cmax) of PDR001 ^[329]

End point description

Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.

End point type

Secondary

End point timeframe

pre-infusion and 1, 24, 168, 336 and 672 hours after completion of the infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The average duration of the infusion was 30 minutes. The duration of one cycle was 28 days.

Notes
[329] - 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 only applies to BLZ945+PDR001 combination group

End point values	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase I-II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	4 ^[330]	5 ^[331]	9 ^[332]	4 ^[333]	6 ^[334]	5 ^[335]	10 ^[336]	4 ^[337]	5 ^[338]	5 ^[339]	26 ^[340]
Units: µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1)	102 ( 13.6 )	93.8 ( 26.3 )	102 ( 20.9 )	96.3 ( 25.7 )	111 ( 25.2 )	102 ( 10.5 )	102 ( 19.4 )	122 ( 5.35 )	111 ( 25.1 )	102 ( 28 )	99.4 ( 27.6 )
Cycle 3 Day 1 (C3D1)	120 ( 42.3 )	132 ( 16.1 )	142 ( 38.1 )	114 ( 40.4 )	138 ( 54.2 )	137 ( 55.4 )	156 ( 48.5 )	999 ( 999 )	118 ( 44.3 )	999 ( 999 )	126 ( 55.6 )

Notes
[330] - n=4 (C1D1), 2 (C3D1)
[331] - n=5 (C1D1), 3 (C3D1)
[332] - n=9 (C1D1), 3 (C3D1)
[333] - n=4 (C1D1), 2 (C3D1)
[334] - n=6 (C1D1), 2 (C3D1)
[335] - n=5 (C1D1), 2 (C3D1)
[336] - n=10 (C1D1), 5 (C3D1)
[337] - n=4 (C1D1), 0 (C3D1)
[338] - n=5 (C1D1), 2 (C3D1)
[339] - n=5 (C1D1), 0 (C3D1)
[340] - n=26 (C1D1), 4 (C3D1)

No statistical analyses for this end point

Secondary: Phase I and II: Time to reach maximum serum concentration (Tmax) of PDR001

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End point title

Phase I and II: Time to reach maximum serum concentration (Tmax) of PDR001 ^[341]

End point description

Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[341] - 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 only applies to BLZ945+PDR001 combination group

End point values	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase I-II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	4 ^[342]	5 ^[343]	9 ^[344]	4 ^[345]	6 ^[346]	5 ^[347]	10 ^[348]	4 ^[349]	5 ^[350]	5 ^[351]	26 ^[352]
Units: hours
median (full range (min-max))
Cycle 1 Day 1 (C1D1)	1.67 (0.833 to 24.2)	1.45 (0.833 to 1.67)	1.5 (0.85 to 1.67)	1.28 (0.933 to 2.1)	1.48 (0.983 to 24.5)	1.42 (0.3 to 23)	1.48 (1.03 to 23.2)	1.46 (1.28 to 23.8)	1.53 (1.28 to 24.5)	1.55 (1.4 to 23)	1.79 (1 to 90.6)
Cycle 3 Day 1 (C3D1)	1.48 (1.42 to 1.55)	1.45 (0 to 1.55)	1.58 (1.53 to 1.65)	1.81 (1.5 to 2.12)	13 (2.05 to 24)	1.53 (1.52 to 1.53)	1.53 (1.42 to 24)	999 (999 to 999)	94.4 (1.6 to 187)	999 (999 to 999)	12.7 (1.5 to 336)

Notes
[342] - n=4 (C1D1), 2 (C3D1)
[343] - n=5 (C1D1), 3 (C3D1)
[344] - n=9 (C1D1), 3 (C3D1)
[345] - n=4 (C1D1), 2 (C3D1)
[346] - n=6 (C1D1), 2 (C3D1)
[347] - n=5 (C1D1), 2 (C3D1)
[348] - n=10 (C1D1), 5 (C3D1)
[349] - n=4 (C1D1), 0 (C3D1)
[350] - n=5 (C1D1), 2 (C3D1)
[351] - n=5 (C1D1), 0 (C3D1)
[352] - n=26 (C1D1), 4 (C3D1)

No statistical analyses for this end point

Secondary: Phase I and II: Area under the serum concentration-time curve from time zero to 28 days post dose (AUC0-28day) of PDR001

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End point title

Phase I and II: Area under the serum concentration-time curve from time zero to 28 days post dose (AUC0-28day) of PDR001 ^[353]

End point description

PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-28day calculation. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[353] - 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 only applies to BLZ945+PDR001 combination group

End point values	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase I-II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	4 ^[354]	4 ^[355]	8 ^[356]	3 ^[357]	5 ^[358]	5 ^[359]	8 ^[360]	3 ^[361]	0 ^[362]	0 ^[363]	19 ^[364]
Units: day*µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1)	1390 ( 250 )	1120 ( 203 )	1160 ( 228 )	1130 ( 274 )	1310 ( 301 )	1350 ( 468 )	1270 ( 204 )	1330 ( 183 )	( )	( )	1230 ( 308 )
Cycle 3 Day 1 (C3D1)	1960 ( 297 )	1780 ( 999 )	1930 ( 630 )	1480 ( 999 )	1240 ( 999 )	1750 ( 838 )	2350 ( 439 )	999 ( 999 )	( )	( )	1950 ( 1220 )

Notes
[354] - n=4 (C1D1), 2 (C3D1)
[355] - n=4 (C1D1), 1 (C3D1)
[356] - n=8 (C1D1), 3 (C3D1)
[357] - n=3 (C1D1), 1 (C3D1)
[358] - n=5 (C1D1), 1 (C3D1)
[359] - n=5 (C1D1), 2 (C3D1)
[360] - n=8 (C1D1), 5 (C3D1)
[361] - n=3 (C1D1), 0 (C3D1)
[362] - No data available
[363] - No data available
[364] - n=19 (C1D1), 2 (C3D1)

No statistical analyses for this end point

Secondary: Phase I and II: Number of participants with anti-PDR001 antibodies

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End point title

Phase I and II: Number of participants with anti-PDR001 antibodies ^[365]

End point description

Immunogenicity was evaluated in serum in a validated three-tiered assay approach. Samples were screened for potential anti-PDR001 antibodies and positive screen results were confirmed using a confirmatory assay. For confirmed anti-drug antibodies (ADA) positive samples, titers were determined. Patient ADA status was defined as follows: • ADA-negative at baseline: ADA-negative sample at baseline • ADA-positive at baseline: ADA-positive sample at baseline • ADA-negative post-baseline: patient with ADA-negative sample at baseline and at least 1 post baseline determinant sample, all of which are ADA-negative samples • Treatment-induced ADA-positive = ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample • Treatment-boosted ADA-positive = ADA-positive sample at baseline and at least 1 treatment-boosted ADA-positive sample

End point type

Secondary

End point timeframe

Baseline (before first dose) and post-baseline (assessed throughout the treatment and safety follow-up, up to 4.4 years in phase I and 0.9 years in phase II).

Notes
[365] - 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 only applies to BLZ945+PDR001 combination group

End point values	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W
Number of subjects analysed	3 ^[366]	5 ^[367]	6 ^[368]	5 ^[369]	6 ^[370]	5 ^[371]	10 ^[372]	7 ^[373]	4 ^[374]	5 ^[375]	4 ^[376]	17 ^[377]
Units: participants
ADA-negative at baseline	3	5	5	4	6	4	10	7	4	5	4	17
ADA-positive at baseline	0	0	1	1	0	1	0	0	0	0	0	0
ADA-negative post-baseline	3	5	4	4	6	4	8	7	4	5	4	17
Treatment-induced ADA-positive	0	0	1	0	0	0	2	0	0	0	0	0
Treatment-boosted ADA-positive	0	0	0	0	0	0	0	0	0	0	0	0

Notes
[366] - n=3 (baseline), 3 (post-baseline)
[367] - n=5 (baseline), 5 (post-baseline)
[368] - n=6 (baseline), 5 (post-baseline)
[369] - n=5 (baseline), 4 (post-baseline)
[370] - n=6 (baseline), 6 (post-baseline)
[371] - n=5 (baseline), 4 (post-baseline)
[372] - n=10 (baseline), 10 (post-baseline)
[373] - n=7 (baseline), 7 (post-baseline)
[374] - n=4 (baseline), 4 (post-baseline)
[375] - n=5 (baseline), 5 (post-baseline)
[376] - n=4 (baseline), 4 (post-baseline)
[377] - n=17 (baseline), 17 (post-baseline)

No statistical analyses for this end point

Post-hoc: All-Collected Deaths

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End point title

All-Collected Deaths

End point description

On-treatment and post-treatment safety follow-up deaths were collected from first dose of study medication to 30 days after last dose (BLZ945 single agent; SA) and to 150 days after last dose (BLZ945+PDR001; combo). Survival follow-up deaths were collected from 31 days (SA) and 151 days (combo) after last dose until end of study. All deaths refer to the sum of on-treatment and post-treatment safety follow-up deaths plus survival follow-up deaths.

End point type

Post-hoc

End point timeframe

On&post-treatment safety: up to 3.1 years (phase I)/1.4 years (phase II) for SA and 4.4 years (phase I)/0.9 years (phase II) for combo. Survival: up to 3.1 years (phase I)/1.9 years (phase II) for SA and 4.4 years (phase I)/1.3 years (phase II) for combo

End point values	Phase I: BLZ945 150 mg 7d on/7d off QD	Phase I: BLZ945 300 mg 7d on/7d off QD	Phase I: BLZ945 300 mg Q1W QD	Phase I: BLZ945 450 mg Q1W QD	Phase I: BLZ945 600 mg Q1W QD	Phase I: BLZ945 1000 mg Q1W QD	Phase I: BLZ945 1600 mg Q1W QD	Phase I: BLZ945 300 mg 4d on/10d off QD	Phase I: BLZ945 600 mg 4d on/10d off QD	Phase I: BLZ945 800 mg 4d on/10d off QD	Phase I: BLZ945 1200 mg 4d on/10d off QD	Phase I: BLZ945 600 mg Q1W BID	Phase I: BLZ945 600 mg 4d on/10d off BID	Phase I: BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 450 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 1200 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	Phase I: BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	Phase II: BLZ945 1200 mg 4d on/10d off QD	Phase II: BLZ945 700 mg 4d on/10d off QD + PDR001 400 mg Q4W	Phase I: BLZ945 300 mg Q1W BID
Number of subjects analysed	5 ^[378]	7 ^[379]	5 ^[380]	6 ^[381]	3 ^[382]	5 ^[383]	6 ^[384]	8 ^[385]	9 ^[386]	5 ^[387]	10 ^[388]	4 ^[389]	6 ^[390]	4 ^[391]	5 ^[392]	9 ^[393]	5 ^[394]	6 ^[395]	5 ^[396]	11 ^[397]	9 ^[398]	4 ^[399]	6 ^[400]	5 ^[401]	22 ^[402]	21 ^[403]	1 ^[404]
Units: participants
On-treatment and post-treatment safety FU deaths	1	0	1	2	0	0	2	0	1	0	1	2	1	0	4	3	3	3	2	6	4	3	4	2	2	8	0
Survival follow-up deaths	4	4	3	3	3	5	3	7	7	4	6	2	5	2	1	3	2	1	0	2	2	0	1	3	14	9	1
All deaths	5	4	4	5	3	5	5	7	8	4	7	4	6	2	5	6	5	4	2	8	6	3	5	5	16	17	1

Notes
[378] - n=5 (on-treatment and safety FU), 4 (survival), 5 (all)
[379] - n=7 (on-treatment and safety FU), 7 (survival), 7 (all)
[380] - n=5 (on-treatment and safety FU), 4 (survival), 5 (all)
[381] - n=6 (on-treatment and safety FU), 4 (survival), 6 (all)
[382] - n=3 (on-treatment and safety FU), 3 (survival), 3 (all)
[383] - n=5 (on-treatment and safety FU), 5 (survival), 5 (all)
[384] - n=6 (on-treatment and safety FU), 4 (survival), 6 (all)
[385] - n=8 (on-treatment and safety FU), 8 (survival), 8 (all)
[386] - n=9 (on-treatment and safety FU), 8 (survival), 9 (all)
[387] - n=5 (on-treatment and safety FU), 5 (survival), 5 (all)
[388] - n=10 (on-treatment and safety FU), 9 (survival), 10 (all)
[389] - n=4 (on-treatment and safety FU), 2 (survival), 4 (all)
[390] - n=6 (on-treatment and safety FU), 5 (survival), 6 (all)
[391] - n=4 (on-treatment and safety FU), 4 (survival), 4 (all)
[392] - n=5 (on-treatment and safety FU), 1 (survival), 5 (all)
[393] - n=9 (on-treatment and safety FU), 6 (survival), 9 (all)
[394] - n=5 (on-treatment and safety FU), 2 (survival), 5 (all)
[395] - n=6 (on-treatment and safety FU), 3 (survival), 6 (all)
[396] - n=5 (on-treatment and safety FU), 3 (survival), 5 (all)
[397] - n=11 (on-treatment and safety FU), 5 (survival), 11 (all)
[398] - n=9 (on-treatment and safety FU), 5 (survival), 9 (all)
[399] - n=4 (on-treatment and safety FU), 1 (survival), 4 (all)
[400] - n=6 (on-treatment and safety FU), 2 (survival), 6 (all)
[401] - n=5 (on-treatment and safety FU), 3 (survival), 5 (all)
[402] - n=22 (on-treatment and safety FU), 20 (survival), 22 (all)
[403] - n=21 (on-treatment and safety FU), 13 (survival), 21 (all)
[404] - n=1 (on-treatment and safety FU), 1 (survival), 1 (all)

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From first dose of study treatment to 30 days after last dose (single agent; SA) and to 150 days after last dose (combo), up to 3.1 years (phase I)/1.4 years (phase II) for SA and 4.4 years (phase I)/0.9 years (phase II) for combo.

Adverse event reporting additional description

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

BLZ945 150mg 7d on/ 7d off QD

Reporting group description

BLZ945 150mg 7d on/ 7d off QD

Reporting group title

BLZ945 300mg Q1W QD

Reporting group description

BLZ945 300mg Q1W QD

Reporting group title

BLZ945 300mg 7d on/ 7d off QD

Reporting group description

BLZ945 300mg 7d on/ 7d off QD

Reporting group title

BLZ945 450mg Q1W QD

Reporting group description

BLZ945 450mg Q1W QD

Reporting group title

BLZ945 600mg Q1W QD

Reporting group description

BLZ945 600mg Q1W QD

Reporting group title

BLZ945 1600mg Q1W QD

Reporting group description

BLZ945 1600mg Q1W QD

Reporting group title

BLZ945 1000mg Q1W QD

Reporting group description

BLZ945 1000mg Q1W QD

Reporting group title

BLZ945 300 mg 4d on/ 10d off QD

Reporting group description

BLZ945 300 mg 4d on/ 10d off QD

Reporting group title

BLZ945 600 mg 4d on/ 10d off QD

Reporting group description

BLZ945 600 mg 4d on/ 10d off QD

Reporting group title

BLZ945 800 mg 4d on/ 10d off QD

Reporting group description

BLZ945 800 mg 4d on/ 10d off QD

Reporting group title

BLZ945 1200 mg 4d on/ 10d off QD

Reporting group description

BLZ945 1200 mg 4d on/ 10d off QD

Reporting group title

BLZ945 300 mg Q1W BID

Reporting group description

BLZ945 300 mg Q1W BID

Reporting group title

BLZ945 600 mg Q1W BID

Reporting group description

BLZ945 600 mg Q1W BID

Reporting group title

BLZ945 600 mg 4d on/ 10d off BID

Reporting group description

BLZ945 600 mg 4d on/ 10d off BID

Reporting group title

BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

Reporting group title

BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

Reporting group title

BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

Reporting group title

BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

Reporting group title

BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

Reporting group title

BLZ945 300 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 300 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Reporting group title

BLZ945 700 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 700 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Reporting group title

BLZ945 450 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 450 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Reporting group title

BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Reporting group description

BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

Reporting group title

BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Reporting group description

BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

Reporting group title

BLZ945 1200 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Reporting group description

BLZ945 1200 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Reporting group title

Phase II SA BLZ945 1200 mg 4d on/ 10d off QD

Reporting group description

Phase II SA BLZ945 1200 mg 4d on/ 10d off QD

Reporting group title

Phase II BLZ945 700 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Reporting group description

Phase II BLZ945 700 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

BLZ945 150mg 7d on/ 7d off QD

BLZ945 300mg Q1W QD

BLZ945 300mg 7d on/ 7d off QD

BLZ945 450mg Q1W QD

BLZ945 600mg Q1W QD

BLZ945 1600mg Q1W QD

BLZ945 1000mg Q1W QD

BLZ945 300 mg 4d on/ 10d off QD

BLZ945 600 mg 4d on/ 10d off QD

BLZ945 800 mg 4d on/ 10d off QD

BLZ945 1200 mg 4d on/ 10d off QD

BLZ945 300 mg Q1W BID

BLZ945 600 mg Q1W BID

BLZ945 600 mg 4d on/ 10d off BID

BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W

BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W

BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W

BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W

BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W

BLZ945 300 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

BLZ945 700 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

BLZ945 450 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W

BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W

BLZ945 1200 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Phase II SA BLZ945 1200 mg 4d on/ 10d off QD

Phase II BLZ945 700 mg 4d on/ 10d off QD + PDR001 400 mg Q4W

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 5 (60.00%)

1 / 7 (14.29%)

2 / 6 (33.33%)

0 / 3 (0.00%)

3 / 6 (50.00%)

3 / 5 (60.00%)

4 / 8 (50.00%)

3 / 9 (33.33%)

3 / 5 (60.00%)

5 / 10 (50.00%)

0 / 1 (0.00%)

3 / 4 (75.00%)

5 / 6 (83.33%)

1 / 4 (25.00%)

2 / 5 (40.00%)

6 / 9 (66.67%)

4 / 5 (80.00%)

3 / 6 (50.00%)

1 / 5 (20.00%)

7 / 9 (77.78%)

6 / 11 (54.55%)

1 / 5 (20.00%)

2 / 6 (33.33%)

4 / 4 (100.00%)

10 / 22 (45.45%)

11 / 21 (52.38%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Acute myeloid leukaemia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cutaneous T-cell lymphoma

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 22 (4.55%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intraductal proliferative breast lesion

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Laryngeal cancer

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant ascites

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peritumoural oedema

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 22 (4.55%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour haemorrhage

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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 pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Deep vein thrombosis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 22 (4.55%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypertensive urgency

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Surgical and medical procedures

Nephrostomy

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Condition aggravated

subjects affected / exposed

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fatigue

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

General physical health deterioration

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

2 / 9 (22.22%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

1 / 22 (4.55%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sudden death

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

Respiratory, thoracic and mediastinal disorders

Aspiration

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 22 (4.55%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemoptysis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

Interstitial lung disease

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Pneumonitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumothorax

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

2 / 21 (9.52%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

2 / 2

deaths causally related to treatment / all

0 / 0

Aspartate aminotransferase increased

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Blood creatine phosphokinase increased

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Platelet count decreased

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SARS-CoV-2 test positive

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Troponin T increased

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Brain herniation

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Head injury

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Radiation necrosis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Spinal compression fracture

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

Cerebral palsy

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Brain oedema

subjects affected / exposed

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

2 / 22 (9.09%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

2 / 2

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebral haemorrhage

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 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 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

Cognitive disorder

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dizziness

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Epilepsy

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 22 (4.55%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemorrhage intracranial

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Headache

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 22 (4.55%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hemiparesis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

2 / 21 (9.52%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Lethargy

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 22 (4.55%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Loss of consciousness

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

Nervous system disorder

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Neurological decompensation

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 22 (4.55%)

0 / 21 (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

Partial seizures

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

Seizure

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 22 (4.55%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Syncope

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

2 / 6 (33.33%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Disseminated intravascular coagulation

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

Thrombocytopenia

subjects affected / exposed

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

1 / 5 (20.00%)

1 / 10 (10.00%)

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

Abdominal pain lower

subjects affected / exposed

0 / 5 (0.00%)

1 / 7 (14.29%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal wall haemorrhage

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ascites

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

Colitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dysphagia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

Haemoperitoneum

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemorrhoids

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ileus

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

Intestinal perforation

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower gastrointestinal haemorrhage

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Oesophagitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subileus

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 22 (0.00%)

0 / 21 (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 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

2 / 8 (25.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 6

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Cholangitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperbilirubinaemia

subjects affected / exposed

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune-mediated hepatitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Rash maculo-papular

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Haematuria

subjects affected / exposed

0 / 5 (0.00%)

1 / 7 (14.29%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

Adrenal insufficiency

subjects affected / exposed

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Autoimmune arthritis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Back pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Abdominal abscess

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Anal abscess

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Appendicitis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Clostridium difficile infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

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 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diverticulitis

subjects affected / exposed

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Empyema

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Enterococcal infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Kidney infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

1 / 9 (11.11%)

2 / 5 (40.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

1 / 5 (20.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Pneumonia bacterial

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 22 (4.55%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis acute

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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

Septic shock

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (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%)

1 / 5 (20.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 15

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular device infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Decreased appetite

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 9 (11.11%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoglycaemia

subjects affected / exposed

0 / 5 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 22 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	BLZ945 150mg 7d on/ 7d off QD	BLZ945 300mg Q1W QD	BLZ945 300mg 7d on/ 7d off QD	BLZ945 450mg Q1W QD	BLZ945 600mg Q1W QD	BLZ945 1600mg Q1W QD	BLZ945 1000mg Q1W QD	BLZ945 300 mg 4d on/ 10d off QD	BLZ945 600 mg 4d on/ 10d off QD	BLZ945 800 mg 4d on/ 10d off QD	BLZ945 1200 mg 4d on/ 10d off QD	BLZ945 300 mg Q1W BID	BLZ945 600 mg Q1W BID	BLZ945 600 mg 4d on/ 10d off BID	BLZ945 150 mg Q1W QD + PDR001 400 mg Q4W	BLZ945 300 mg Q1W QD + PDR001 400 mg Q4W	BLZ945 600 mg Q1W QD + PDR001 400 mg Q4W	BLZ945 1000 mg Q1W QD + PDR001 400 mg Q4W	BLZ945 1400 mg Q1W QD + PDR001 400 mg Q4W	BLZ945 300 mg 4d on/ 10d off QD + PDR001 400 mg Q4W	BLZ945 700 mg 4d on/ 10d off QD + PDR001 400 mg Q4W	BLZ945 450 mg 4d on/ 10d off QD + PDR001 400 mg Q4W	BLZ945 800 mg Q1W BID + PDR001 400 mg Q4W	BLZ945 600 mg Q1W BID + PDR001 400 mg Q4W	BLZ945 1200 mg 4d on/ 10d off QD + PDR001 400 mg Q4W	Phase II SA BLZ945 1200 mg 4d on/ 10d off QD	Phase II BLZ945 700 mg 4d on/ 10d off QD + PDR001 400 mg Q4W
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 5 (100.00%)	5 / 5 (100.00%)	7 / 7 (100.00%)	6 / 6 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	5 / 5 (100.00%)	8 / 8 (100.00%)	9 / 9 (100.00%)	5 / 5 (100.00%)	10 / 10 (100.00%)	1 / 1 (100.00%)	4 / 4 (100.00%)	6 / 6 (100.00%)	4 / 4 (100.00%)	5 / 5 (100.00%)	9 / 9 (100.00%)	5 / 5 (100.00%)	6 / 6 (100.00%)	5 / 5 (100.00%)	9 / 9 (100.00%)	11 / 11 (100.00%)	5 / 5 (100.00%)	6 / 6 (100.00%)	4 / 4 (100.00%)	20 / 22 (90.91%)	19 / 21 (90.48%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer fatigue
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Oncologic complication
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0
Infected neoplasm
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Cancer pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tumour pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	2	0	0	0	0	0	1	0	1	1	0	0
Tumour haemorrhage
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypertension
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	2	1	0	0	2	0	2	3	0	0	0	1	0	1	1	2	0	3	0	1	0
Haematoma
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Embolism
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0
Lymphoedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Raynaud's phenomenon
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hypotension
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 9 (11.11%)	2 / 11 (18.18%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	2	0	0	0	0	0
Thrombophlebitis migrans
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
General disorders and administration site conditions
Administration site haematoma
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asthenia
subjects affected / exposed	1 / 5 (20.00%)	1 / 5 (20.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	6 / 22 (27.27%)	2 / 21 (9.52%)
occurrences all number	1	1	1	0	0	0	0	0	6	0	1	0	1	2	0	1	0	0	1	1	1	0	0	1	2	8	2
Axillary pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Face oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Chills
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	2	0	0	0	0	0	0	1	0	0	0	0	0
Fatigue
subjects affected / exposed	2 / 5 (40.00%)	2 / 5 (40.00%)	1 / 7 (14.29%)	2 / 6 (33.33%)	2 / 3 (66.67%)	1 / 6 (16.67%)	2 / 5 (40.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	2 / 5 (40.00%)	2 / 10 (20.00%)	0 / 1 (0.00%)	2 / 4 (50.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	2 / 5 (40.00%)	2 / 9 (22.22%)	2 / 5 (40.00%)	0 / 6 (0.00%)	2 / 5 (40.00%)	4 / 9 (44.44%)	4 / 11 (36.36%)	4 / 5 (80.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	7 / 22 (31.82%)	3 / 21 (14.29%)
occurrences all number	2	2	1	2	2	1	2	0	3	2	2	0	2	2	1	2	2	3	0	2	4	6	4	3	0	8	3
Feeling jittery
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Gait disturbance
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	1	0
Influenza like illness
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	2 / 9 (22.22%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Oedema peripheral
subjects affected / exposed	1 / 5 (20.00%)	1 / 5 (20.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 22 (4.55%)	2 / 21 (9.52%)
occurrences all number	1	1	1	0	1	1	1	0	0	0	0	0	1	1	0	2	0	0	0	0	0	3	0	1	0	1	2
Pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pyrexia
subjects affected / exposed	5 / 5 (100.00%)	2 / 5 (40.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	4 / 9 (44.44%)	3 / 5 (60.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	1 / 5 (20.00%)	2 / 6 (33.33%)	1 / 5 (20.00%)	1 / 9 (11.11%)	3 / 11 (27.27%)	2 / 5 (40.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	3 / 22 (13.64%)	3 / 21 (14.29%)
occurrences all number	10	3	0	0	1	0	1	0	6	4	1	0	3	2	0	2	1	1	2	1	1	3	4	1	2	3	4
Swelling face
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Xerosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Immune system disorders
Contrast media allergy
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypersensitivity
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Reproductive system and breast disorders
Breast inflammation
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Breast pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Nipple pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Pelvic pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Vaginal haemorrhage
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Scrotal oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Rectocele
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Vulvovaginal burning sensation
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Cough
subjects affected / exposed	1 / 5 (20.00%)	1 / 5 (20.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 9 (11.11%)	2 / 11 (18.18%)	1 / 5 (20.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	1	2	0	0	0	1	0	0	1	0	0	1	0	0	0	1	0	1	0	6	3	1	0	1	0	0
Dysphonia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dyspnoea
subjects affected / exposed	2 / 5 (40.00%)	0 / 5 (0.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 5 (40.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 9 (22.22%)	1 / 5 (20.00%)	2 / 6 (33.33%)	0 / 5 (0.00%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 5 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	2	0	2	0	0	0	2	0	1	0	0	0	0	1	0	0	2	1	2	0	1	2	0	2	0	0	0
Epistaxis
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Dyspnoea exertional
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Laryngeal oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Haemoptysis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Pleural effusion
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	1	0
Pneumonitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Pneumothorax
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Productive cough
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Pulmonary embolism
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Rhinitis allergic
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 9 (22.22%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	1	0
Sinus pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Stridor
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Wheezing
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 22 (9.09%)	1 / 21 (4.76%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	1	0	0	0	0	2	1
Bradyphrenia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	1	1
Confusional state
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1	0
Delirium
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Depression
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	1
Euphoric mood
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Psychotic disorder
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
Insomnia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 9 (11.11%)	2 / 11 (18.18%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	3 / 22 (13.64%)	3 / 21 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	1	1	0	0	0	1	1	0	8	2	1	1	0	3	3
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 5 (0.00%)	4 / 5 (80.00%)	3 / 7 (42.86%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	3 / 8 (37.50%)	3 / 9 (33.33%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	3 / 6 (50.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	3 / 9 (33.33%)	2 / 5 (40.00%)	1 / 6 (16.67%)	2 / 5 (40.00%)	1 / 9 (11.11%)	7 / 11 (63.64%)	3 / 5 (60.00%)	2 / 6 (33.33%)	3 / 4 (75.00%)	3 / 22 (13.64%)	11 / 21 (52.38%)
occurrences all number	0	4	3	0	0	1	1	3	4	0	1	0	1	3	1	1	5	3	1	2	1	8	8	3	3	3	14
Amylase
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Amylase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	3 / 7 (42.86%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 5 (40.00%)	4 / 8 (50.00%)	3 / 9 (33.33%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	1 / 5 (20.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	2 / 9 (22.22%)	4 / 11 (36.36%)	0 / 5 (0.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	5 / 22 (22.73%)	9 / 21 (42.86%)
occurrences all number	0	0	4	0	0	1	2	9	5	0	5	0	2	5	0	1	1	1	1	1	4	8	0	0	2	9	9
Aspartate aminotransferase
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Aspartate aminotransferase decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 5 (20.00%)	4 / 5 (80.00%)	5 / 7 (71.43%)	1 / 6 (16.67%)	2 / 3 (66.67%)	3 / 6 (50.00%)	3 / 5 (60.00%)	4 / 8 (50.00%)	5 / 9 (55.56%)	2 / 5 (40.00%)	5 / 10 (50.00%)	0 / 1 (0.00%)	2 / 4 (50.00%)	3 / 6 (50.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	5 / 9 (55.56%)	4 / 5 (80.00%)	3 / 6 (50.00%)	3 / 5 (60.00%)	2 / 9 (22.22%)	7 / 11 (63.64%)	4 / 5 (80.00%)	3 / 6 (50.00%)	2 / 4 (50.00%)	4 / 22 (18.18%)	12 / 21 (57.14%)
occurrences all number	2	4	5	1	2	3	3	6	10	2	5	0	2	3	1	0	6	4	4	3	2	10	12	6	2	5	17
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	2 / 8 (25.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	1 / 5 (20.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	3 / 21 (14.29%)
occurrences all number	0	0	1	0	0	0	1	2	1	0	1	0	0	2	0	1	1	1	1	1	0	0	0	0	0	0	3
Blood albumin decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0	1	0	0	0	1	0	0
Blood chloride decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 22 (13.64%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	3	1	0	0	1	0	0	0	0	3	1
Blood chloride increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Blood creatine increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	3 / 7 (42.86%)	2 / 6 (33.33%)	0 / 3 (0.00%)	3 / 6 (50.00%)	1 / 5 (20.00%)	3 / 8 (37.50%)	5 / 9 (55.56%)	0 / 5 (0.00%)	3 / 10 (30.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	3 / 9 (33.33%)	3 / 5 (60.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	3 / 11 (27.27%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	8 / 22 (36.36%)	7 / 21 (33.33%)
occurrences all number	0	0	3	3	0	3	1	7	11	0	4	0	2	2	0	0	3	3	0	0	0	4	1	1	0	9	9
Blood creatinine increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 22 (9.09%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0	0	0	0	1	0	0	0	1	0	1	0	0	0	0	2	0
Blood creatinine
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 22 (9.09%)	3 / 21 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	3
Blood magnesium decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood phosphorus decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Blood potassium decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	1	0
Blood sodium increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Blood uric acid increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	3	0	0	0	0	0
Blood urea increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	1	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
International normalised ratio increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Lipase increased
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	2 / 5 (40.00%)	3 / 8 (37.50%)	3 / 9 (33.33%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	3 / 4 (75.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	2 / 9 (22.22%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	2 / 22 (9.09%)	6 / 21 (28.57%)
occurrences all number	3	0	2	0	1	0	2	6	4	0	2	0	4	2	0	2	0	0	1	0	3	2	0	1	1	5	6
Lymphocyte count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	3 / 22 (13.64%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	2	0	0	0	0	0	0	1	4	0	0	1	3	2
Neutrophil count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 22 (9.09%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	2	1	0	0	2	0
Troponin I increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	2	0	0	1	0	0	1	0	0	0	0	0	0	2	0	0	0	0	1	0	0	0	1	0
Troponin T increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	2 / 9 (22.22%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0	0	0	0	2
Weight decreased
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	1	1	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
White blood cell count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	3 / 10 (30.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0
Weight increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Injury, poisoning and procedural complications
Breast injury
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	1
Fall
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 22 (9.09%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0
Infusion related reaction
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Head injury
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Procedural pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	2 / 8 (25.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Road traffic accident
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Skin laceration
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Skin injury
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cardiac arrest
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Nervous system disorders
Agnosia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Aphasia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 22 (9.09%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0	0	0	0	0	0	1	0	1	0	0	2	2
Ataxia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Brain oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 1 (100.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2
Cerebrovascular accident
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Dizziness
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	1 / 6 (16.67%)	3 / 5 (60.00%)	3 / 9 (33.33%)	1 / 11 (9.09%)	1 / 5 (20.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	1 / 22 (4.55%)	1 / 21 (4.76%)
occurrences all number	0	0	0	1	1	1	1	0	1	1	0	0	1	2	0	0	1	0	1	3	4	1	1	0	2	1	1
Depressed level of consciousness
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Dysaesthesia
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dysgeusia
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	1	0	0	0	0	0	0	1	0	1	0	0	0	0	1	0	0	1	0
Epilepsy
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gait apraxia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Headache
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 5 (40.00%)	0 / 8 (0.00%)	3 / 9 (33.33%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	2 / 4 (50.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 9 (22.22%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	6 / 22 (27.27%)	2 / 21 (9.52%)
occurrences all number	2	0	2	0	0	0	4	0	5	0	0	0	3	1	0	1	8	0	0	0	0	1	0	0	3	6	2
Hemiparesis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Hypoaesthesia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0
Hemiplegia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Myoclonus
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Migraine
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Neurological decompensation
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	1	0	0	0	1	0
Neuropathy peripheral
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Neurological symptom
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Paraesthesia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0
Parosmia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Seizure
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	2 / 4 (50.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	1	0	2	0	0	0	0	1
Peripheral sensory neuropathy
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Slow speech
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Spinal cord compression
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Syncope
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Hypergammaglobulinaemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Leukocytosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Anaemia
subjects affected / exposed	2 / 5 (40.00%)	1 / 5 (20.00%)	3 / 7 (42.86%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 6 (16.67%)	4 / 5 (80.00%)	2 / 8 (25.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	4 / 10 (40.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	3 / 9 (33.33%)	1 / 5 (20.00%)	3 / 6 (50.00%)	1 / 5 (20.00%)	3 / 9 (33.33%)	4 / 11 (36.36%)	2 / 5 (40.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 22 (0.00%)	2 / 21 (9.52%)
occurrences all number	4	1	4	1	0	1	5	2	1	0	4	0	1	3	0	5	4	1	5	1	6	5	2	2	0	0	2
Leukopenia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Lymphadenopathy
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Lymphopenia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	1 / 11 (9.09%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	2	1	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	3	0
Ear and labyrinth disorders
Deafness unilateral
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hypoacusis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Eye disorders
Conjunctival haemorrhage
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Exophthalmos
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Dry eye
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Diplopia
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	4 / 21 (19.05%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	4
Eye irritation
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Eye swelling
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Eyelid oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Lacrimation increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 22 (9.09%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Orbital oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Periorbital oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Swelling of eyelid
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Periorbital swelling
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Visual impairment
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Vision blurred
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	2 / 4 (50.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	1	0	1	0	0	0	1
Abdominal pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 5 (20.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)	2 / 5 (40.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	2	1	1	1	2	0	0	0	0	0	0	0	3	1	0	0	2	0	0	0	0	0
Abdominal tenderness
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Abdominal pain upper
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	2 / 11 (18.18%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 22 (9.09%)	0 / 21 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	1	0	0	0	0	0	0	1	0	0	0	1	2	0	0	1	2	0
Abdominal pain lower
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Anal fissure
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Anal haemorrhage
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ascites
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dry mouth
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	0
Diarrhoea
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 5 (20.00%)	1 / 8 (12.50%)	2 / 9 (22.22%)	1 / 5 (20.00%)	3 / 10 (30.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	3 / 5 (60.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	2 / 6 (33.33%)	1 / 5 (20.00%)	4 / 9 (44.44%)	2 / 11 (18.18%)	0 / 5 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 22 (4.55%)	2 / 21 (9.52%)
occurrences all number	0	0	2	1	1	1	3	2	2	1	3	0	0	2	0	4	0	1	2	1	11	2	0	3	0	1	3
Constipation
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	2 / 8 (25.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	2 / 5 (40.00%)	0 / 6 (0.00%)	2 / 5 (40.00%)	2 / 9 (22.22%)	1 / 11 (9.09%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 22 (4.55%)	2 / 21 (9.52%)
occurrences all number	1	0	0	0	0	0	1	2	0	0	1	0	0	2	0	1	0	2	0	2	2	1	1	1	0	2	2
Dyspepsia
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 22 (9.09%)	2 / 21 (9.52%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	2	2
Frequent bowel movements
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Flatulence
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastric ulcer
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 5 (40.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	2	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Gingival bleeding
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haematemesis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haematochezia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hiatus hernia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Hyperaesthesia teeth
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Impaired gastric emptying
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 5 (20.00%)	1 / 5 (20.00%)	2 / 7 (28.57%)	1 / 6 (16.67%)	1 / 3 (33.33%)	3 / 6 (50.00%)	4 / 5 (80.00%)	2 / 8 (25.00%)	6 / 9 (66.67%)	3 / 5 (60.00%)	5 / 10 (50.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 9 (22.22%)	3 / 5 (60.00%)	5 / 6 (83.33%)	1 / 5 (20.00%)	3 / 9 (33.33%)	4 / 11 (36.36%)	3 / 5 (60.00%)	2 / 6 (33.33%)	2 / 4 (50.00%)	9 / 22 (40.91%)	5 / 21 (23.81%)
occurrences all number	2	1	2	1	2	5	6	3	14	3	7	0	1	4	0	2	2	4	6	1	5	4	5	2	2	11	5
Odynophagia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Oesophagitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Proctalgia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Rectal haemorrhage
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Rectal tenesmus
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Salivary hypersecretion
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1	0	2	0	0	0	1	0	0	0	0	2	0	0	0	1	0
Tongue discomfort
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Vomiting
subjects affected / exposed	2 / 5 (40.00%)	1 / 5 (20.00%)	1 / 7 (14.29%)	2 / 6 (33.33%)	0 / 3 (0.00%)	4 / 6 (66.67%)	4 / 5 (80.00%)	4 / 8 (50.00%)	2 / 9 (22.22%)	3 / 5 (60.00%)	2 / 10 (20.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	4 / 6 (66.67%)	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	1 / 5 (20.00%)	4 / 6 (66.67%)	2 / 5 (40.00%)	3 / 9 (33.33%)	4 / 11 (36.36%)	3 / 5 (60.00%)	3 / 6 (50.00%)	2 / 4 (50.00%)	6 / 22 (27.27%)	5 / 21 (23.81%)
occurrences all number	4	1	1	2	0	8	8	5	4	8	6	0	1	4	1	3	2	1	7	3	4	5	6	7	2	8	9
Hepatobiliary disorders
Deficiency of bile secretion
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Cholestasis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hepatic pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hyperbilirubinaemia
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0
Hepatitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hypertransaminasaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Blister
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dry skin
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Eczema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	3	0	0	1
Hyperhidrosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Pain of skin
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Psoriasis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	3 / 5 (60.00%)	0 / 5 (0.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	2 / 11 (18.18%)	0 / 5 (0.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	3	0	2	0	1	0	1	1	0	1	1	0	0	0	2	1	1	0	0	0	2	3	0	3	0	0	2
Rash
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	3 / 9 (33.33%)	0 / 5 (0.00%)	2 / 6 (33.33%)	1 / 5 (20.00%)	4 / 9 (44.44%)	2 / 11 (18.18%)	0 / 5 (0.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	1 / 22 (4.55%)	4 / 21 (19.05%)
occurrences all number	0	1	0	0	1	0	0	0	1	0	1	0	1	0	0	1	3	0	2	1	5	3	0	2	1	1	5
Rash erythematous
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0
Rash maculo-papular
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	1 / 21 (4.76%)
occurrences all number	0	0	1	0	0	0	0	1	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Rash pruritic
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Skin hypopigmentation
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Skin lesion
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Urticaria
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Choluria
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Chronic kidney disease
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dysuria
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	1	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Haematuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haemorrhage urinary tract
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Hydronephrosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pollakiuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0
Polyuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Urinary retention
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 9 (22.22%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Urinary incontinence
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Renal failure
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Hypothyroidism
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	2 / 5 (40.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	2	1	0	0	1
Musculoskeletal and connective tissue disorders
Bone pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Back pain
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	3 / 9 (33.33%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	3 / 11 (27.27%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	2	0	0	1	0	1	1	0	0	0	1	0	0	0	0	2	3	0	0	0	1	3	0	1	1	0	1
Arthralgia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 9 (22.22%)	3 / 11 (27.27%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	1	0	0	1	0	1	1	0	0	0	2	3	0	0	0	1	2
Limb discomfort
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Haemarthrosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscle contracture
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0
Muscular weakness
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	1 / 21 (4.76%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Musculoskeletal chest pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0
Musculoskeletal pain
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0
Myalgia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	1	0	0	1	0	0	1	0	0	0	0	0	0	1	1	1	0
Neck pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Osteitis deformans
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Sacral pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pain in extremity
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	1	0	0	0	0	1	1	0	0	0	1	0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Candida infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Cellulitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Cystitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Device related infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Escherichia urinary tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Eye infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Gastroenteritis viral
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Herpes zoster
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0
Influenza
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 3 (66.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Oral candidiasis
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0
Oral fungal infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Oral herpes
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pilonidal disease
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Postoperative abscess
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Pneumonia aspiration
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Pneumonia
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Pulpitis dental
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pyuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Rhinitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Skin infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Tooth abscess
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	1	0	0
Urinary tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	1	0	0	1
Vascular device infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Abnormal loss of weight
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Decreased appetite
subjects affected / exposed	3 / 5 (60.00%)	2 / 5 (40.00%)	3 / 7 (42.86%)	1 / 6 (16.67%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	3 / 9 (33.33%)	2 / 5 (40.00%)	2 / 10 (20.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	2 / 5 (40.00%)	2 / 9 (22.22%)	1 / 5 (20.00%)	2 / 6 (33.33%)	3 / 5 (60.00%)	2 / 9 (22.22%)	3 / 11 (27.27%)	2 / 5 (40.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	2 / 22 (9.09%)	4 / 21 (19.05%)
occurrences all number	3	2	3	1	1	1	0	0	7	2	2	0	0	2	1	2	2	1	2	3	2	3	2	1	1	2	4
Dehydration
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	2	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Glucose tolerance impaired
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hyperammonaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Hypercalcaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	2
Hyperglycaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	2 / 11 (18.18%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 22 (9.09%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1	0	0	0	0	0	0	1	2	0	0	0	2	0
Hyperchloraemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0
Hyperkalaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Hyperphosphataemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Hypernatraemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 22 (9.09%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	2	0
Hypermagnesaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Hypocalcaemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 9 (22.22%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	3	0	1	0	0	0	0	2	1	0	0	1	1	0
Hypoalbuminaemia
subjects affected / exposed	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	1	0	0	0	0	1	0	1	1	0	0	0	1	0	0	0	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	1	0	0	0	0	0	0	0	4	0	0	0	0	0	0	0	0	0	0
Hypochloraemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	1
Hypoglycaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	1	0	0	0	0	1	0
Hypokalaemia
subjects affected / exposed	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 9 (22.22%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 9 (22.22%)	3 / 11 (27.27%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	3 / 21 (14.29%)
occurrences all number	1	1	0	1	0	0	0	0	2	0	2	0	0	4	0	0	3	1	0	0	8	3	0	0	0	0	4
Hypomagnesaemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 22 (4.55%)	0 / 21 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	1	4	2	0	0	0	1	0
Hyponatraemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	1 / 21 (4.76%)
occurrences all number	2	0	0	2	0	0	1	0	0	0	1	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	1
Hypophagia
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hypophosphataemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	7	0	0	0	0	0	1	0	0	0	0	1	0	2	0	0	0	0	0	0
Metabolic acidosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Steroid diabetes
subjects affected / exposed	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 22 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

04 Aug 2017

The purpose of this amendment was to address the inclusion of Japanese patients in the study in a separate dose escalation arm, to permit the exploration of alternative BLZ945 dosing schedules, and to clarify eligibility criteria. To further characterize the safety and efficacy of BLZ945 an additional dosing schedule has been added to the protocol.

24 Oct 2017

The purpose of this amendment was to revise definitions for dose limiting toxicities (DLTs) regarding Grade 3 febrile neutropenia and update the definition of Grade 3 febrile neutropenia in line with CTCAE version 4.03, following Health Authority feedback.

05 Feb 2018

The main purpose of this amendment was to adjust biomarker and biochemistry sample collection time points based on information obtained during the study so far.

31 Jul 2018

The primary purpose of this amendment was to incorporate health authority-requested language requiring study treatment discontinuation in the event of Stevens-Johnson syndrome (SJS) or Lyell syndrome/toxic epidermal necrolysis (TEN). After the occurrence of a case of Steven Johnson Syndrome in a study with PDR001 in combination with another investigational agent, the dose modification guidelines for protocols using PDR001 were updated to mandate permanent discontinuation of study treatment for patients who experience SJS or Lyell syndrome/TEN.

16 Nov 2018

The purpose of this amendment was as follows: To clarify that patients with relapsed or refractory (r/r) lymphoma were eligible to enroll in the study and to implement the methodology for efficacy assessments that followed the appropriate guidelines for these patient populations. The option of twice per day dosing was introduced to enable the exploration of higher doses while reducing the total number of BLZ945 capsules to be taken at each administration. To align with the recently published ImmunoOncology toxicity management guidelines. The dose modification section of the protocol and corresponding tables were updated. Removal of the baseline and on treatment blood sample collections for the assessment of serum cytokines used for retrospective analysis of a cytokine release syndrome adverse event. Blood samples for serum cytokines were included due to the unknown risk of Cytokine Release Syndrome (CRS) with ImmunoOncology agents alone and in combination, and to allow an assessment of any association between cytokines and clinical events.

20 Feb 2020

The primary purpose of this amendment is as follows: Update the patient population in the phase II part. The phase II part of study focused on glioblastoma due to the encouraging results observed in the phase I part of the study. The phase II part in advanced pancreatic cancer and triple negative breast cancer was removed from the study protocol due to business considerations. Clarification was included to refine the eligibility criteria of glioblastoma population in the phase II part of the study regarding the prior anti-neoplastic therapies and dosage of concomitantly used dexamethasone. Based on the emerging data from Phase I part of the study, the number of glioblastoma patients to be enrolled in BLZ945 single agent phase II part were increased to better characterize the anti-tumor activity of BLZ945 as single agent. Modify the study assessments to further characterize biological effects of BLZ945. Elevation of liver enzymes were observed under treatment with BLZ945 both pre-clinically and clinically. To further characterize the biological mechanism behind these findings, optional research samples were collected to look for novel biomarkers that were not yet clinically validated but received letters of support from FDA and EMEA for evaluation in clinical trials. To enable comprehensive assessment of tumor tissue from patients with glioblastoma enrolled in either Phase I or Phase II parts of the study, an archival tumor sample is requested for exploratory assessments. Collection of biological samples was simplified in the phase II part of the study. Only plasma samples were collected for pharmacodynamic assessments. PK serum samples were collected during and at the end of cycle 1 and EOT only. Doppler echocardiography was added to monitor for any potential cardiac risk at baseline and day 1 of every cycle.

05 May 2022

This protocol amendment revised the end of study definition to include the option for patients still on study treatment and who, in the opinion of the investigator, were still deriving clinical benefit at the time of end of study, to transfer to another study or to use an alternative way to provide study treatment to these patients. The biomarker analysis was considered as exploratory and hence the analysis of pharmacodynamics effect of BLZ945 as single agent and in combination with PDR001 were exploratory objectives. Therefore, all pharmacodynamic endpoints were combined under these exploratory objectives.

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.

Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/#/

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Clinical trials

Clinical Trial Results: A phase I/II, open-label, multi-center study of the safety and efficacy of BLZ945 as single agent and in combination with PDR001 in adults patients with advanced solid tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase I: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the on-treatment period

Primary: Phase I: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the on-treatment period

Primary: Phase I: Number of participants with dose reductions and dose interruptions of BLZ945

Primary: Phase I: Number of participants with dose reductions and dose interruptions of BLZ945

Primary: Phase I: Number of participants with dose reductions and dose interruptions of PDR001

Primary: Phase I: Number of participants with dose reductions and dose interruptions of PDR001

Primary: Phase I: Dose intensity of BLZ945

Primary: Phase I: Dose intensity of BLZ945

Primary: Phase I: Dose intensity of PDR001

Primary: Phase I: Dose intensity of PDR001

Primary: Phase I: Number of participants with Dose-Limiting Toxicities (DLTs) (non-Japanese cohort)

Primary: Phase I: Number of participants with Dose-Limiting Toxicities (DLTs) (non-Japanese cohort)

Primary: Phase I: Number of participants with Dose-Limiting Toxicities (DLTs) (Japanese cohort)

Primary: Phase I: Number of participants with Dose-Limiting Toxicities (DLTs) (Japanese cohort)

Primary: Phase II: Progression-Free Survival rate at 6 months (PFS6) per RANO criteria for glioblastoma

Primary: Phase II: Progression-Free Survival rate at 6 months (PFS6) per RANO criteria for glioblastoma

Secondary: Phase I: Progression-Free Survival (PFS) per RECIST v1.1

Secondary: Phase I: Progression-Free Survival (PFS) per RECIST v1.1

Secondary: Phase I: Progression-Free Survival (PFS) per irRC

Secondary: Phase I: Progression-Free Survival (PFS) per irRC

Secondary: Phase I: Progression-Free Survival (PFS) per RANO

Secondary: Phase I: Progression-Free Survival (PFS) per RANO

Secondary: Phase I and II: Progression-Free Survival (PFS) per iRANO

Secondary: Phase I and II: Progression-Free Survival (PFS) per iRANO

Secondary: Phase I: Progression-Free Survival (PFS) per guidelines for efficacy evaluation in lymphoma studies

Secondary: Phase I: Progression-Free Survival (PFS) per guidelines for efficacy evaluation in lymphoma studies

Secondary: Phase I: Best Overall Response (BOR) with confirmation per RECIST v1.1

Secondary: Phase I: Best Overall Response (BOR) with confirmation per RECIST v1.1

Secondary: Phase I: Best Overall Response (BOR) with confirmation per irRC

Secondary: Phase I: Best Overall Response (BOR) with confirmation per irRC

Secondary: Phase I and II: Best Overall Response (BOR) (sustained) per RANO

Secondary: Phase I and II: Best Overall Response (BOR) (sustained) per RANO

Secondary: Phase I and II: Best Overall Response (BOR) (sustained) per iRANO

Secondary: Phase I and II: Best Overall Response (BOR) (sustained) per iRANO

Secondary: Phase I: Best Overall Response (BOR) per guidelines for efficacy evaluation in lymphoma studies

Secondary: Phase I: Best Overall Response (BOR) per guidelines for efficacy evaluation in lymphoma studies

Secondary: Phase I: Overall Response Rate (ORR) per RECIST v1.1

Secondary: Phase I: Overall Response Rate (ORR) per RECIST v1.1

Secondary: Phase I: Overall Response Rate (ORR) per irRC

Secondary: Phase I: Overall Response Rate (ORR) per irRC

Secondary: Phase I: Overall Response Rate (ORR) per guidelines for efficacy evaluation in lymphoma studies

Secondary: Phase I: Overall Response Rate (ORR) per guidelines for efficacy evaluation in lymphoma studies

Secondary: Phase I: Disease Control Rate (DCR) per RECIST v1.1

Secondary: Phase I: Disease Control Rate (DCR) per RECIST v1.1

Secondary: Phase I: Disease Control Rate (DCR) per irRC

Secondary: Phase I: Disease Control Rate (DCR) per irRC

Secondary: Phase I and II: Disease Control Rate (DCR) per RANO

Secondary: Phase I and II: Disease Control Rate (DCR) per RANO

Secondary: Phase I and II: Disease Control Rate (DCR) per iRANO

Secondary: Phase I and II: Disease Control Rate (DCR) per iRANO

Secondary: Phase I: Disease Control Rate (DCR) per guidelines for efficacy evaluation in lymphoma studies

Secondary: Phase I: Disease Control Rate (DCR) per guidelines for efficacy evaluation in lymphoma studies

Secondary: Phase II: Duration of Response (DOR) per RANO

Secondary: Phase II: Duration of Response (DOR) per RANO

Secondary: Phase II: Duration of Response (DOR) per iRANO

Secondary: Phase II: Duration of Response (DOR) per iRANO

Secondary: Phase II: Overall Survival (OS)

Secondary: Phase II: Overall Survival (OS)

Secondary: Phase II: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the on-treatment period

Secondary: Phase II: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the on-treatment period

Secondary: Phase II: Number of participants with dose reductions and dose interruptions of BLZ945

Secondary: Phase II: Number of participants with dose reductions and dose interruptions of BLZ945

Secondary: Phase II: Number of participants with dose reductions and dose interruptions of PDR001

Secondary: Phase II: Number of participants with dose reductions and dose interruptions of PDR001

Secondary: Phase II: Dose intensity of BLZ945

Secondary: Phase II: Dose intensity of BLZ945

Secondary: Phase II: Dose intensity of PDR001

Secondary: Phase II: Dose intensity of PDR001

Secondary: Phase I and II: Maximum observed serum concentration (Cmax) of BLZ945 (7d on/7d off regimen)

Secondary: Phase I and II: Maximum observed serum concentration (Cmax) of BLZ945 (7d on/7d off regimen)

Clinical Trial Results:
A phase I/II, open-label, multi-center study of the safety and efficacy of BLZ945 as single agent and in combination with PDR001 in adults patients with advanced solid tumors