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Clinical Trial Results:
A phase I/II, multicenter, open-label study of MAK683 in adult patients with advanced malignancies

Summary
EudraCT number	2016-001860-12
Trial protocol	DE FR ES IT
Global end of trial date	09 Oct 2024

Results information
Results version number	v1(current)
This version publication date	21 Aug 2025
First version publication date	21 Aug 2025
Other versions

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

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Trial information

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Sponsor protocol code

CMAK683X2101

ISRCTN number

US NCT number

NCT02900651

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

Lichtstrasse 35, Basel, Switzerland, 4056

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 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

09 Oct 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 Oct 2024

Was the trial ended prematurely?

Yes

Main objective of the trial

To characterize safety and tolerability and determine the MTD and/or RP2D of MAK683

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

03 Oct 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 7

Country: Number of subjects enrolled

China: 2

Country: Number of subjects enrolled

France: 33

Country: Number of subjects enrolled

Germany: 13

Country: Number of subjects enrolled

Hong Kong: 10

Country: Number of subjects enrolled

Italy: 19

Country: Number of subjects enrolled

Japan: 11

Country: Number of subjects enrolled

Singapore: 5

Country: Number of subjects enrolled

Spain: 15

Country: Number of subjects enrolled

United States: 24

Worldwide total number of subjects

139

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants were enrolled in 16 investigative sites in 10 countries.

Screening details

Screening evaluations had to be completed within 28 days prior to the first dose of study treatment. 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

10 mg QD

Arm description

MAK683 10 mg orally once daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 10 mg orally once daily

20 mg QD

Arm description

MAK683 20 mg orally once daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 20 mg orally once daily

40 mg QD

Arm description

MAK683 40 mg orally once daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 40 mg orally once daily

80 mg QD

Arm description

MAK683 80 mg orally once daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 80 mg orally once daily

120 mg QD

Arm description

MAK683 120 mg orally once daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 120 mg orally once daily

160 mg QD

Arm description

MAK683 160 mg orally once daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 160 mg orally once daily

240 mg QD

Arm description

MAK683 240 mg orally once daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 240 mg orally once daily

300 mg QD

Arm description

MAK683 300 mg orally once daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 300 mg orally once daily

500 mg QD

Arm description

MAK683 500 mg orally once daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 500 mg orally once daily

800 mg QD

Arm description

MAK683 800 mg orally once daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 800 mg orally once daily

60 mg BID

Arm description

MAK683 60 mg orally twice daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 60 mg orally twice daily

80 mg BID

Arm description

MAK683 80 mg orally twice daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 80 mg orally twice daily

120 mg BID

Arm description

MAK683 120 mg orally twice daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 120 mg orally twice daily

150 mg BID

Arm description

MAK683 150 mg orally twice daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 150 mg orally twice daily

300 mg BID

Arm description

MAK683 300 mg orally twice daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 300 mg orally twice daily

450 mg BID

Arm description

MAK683 450 mg orally twice daily

Arm type

Experimental

Investigational medicinal product name

MAK683

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

MAK683 450 mg orally twice daily

Number of subjects in period 1	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Started	4	7	3	8	8	5	6	4	18	4	8	11	11	8	30	4
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	4	7	3	8	8	5	6	4	18	4	8	11	11	8	30	4
Physician decision	1	1	-	-	1	-	1	-	-	-	2	1	1	-	1	1
Death	-	-	-	-	-	-	1	-	1	-	-	1	-	1	1	-
Progressive Disease	3	5	3	8	7	4	4	4	14	4	4	9	7	7	22	2
adverse event	-	-	-	-	-	-	-	-	1	-	2	-	-	-	4	1
Study Terminated by Sponsor	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	-
Lost to follow-up	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-	-
Subject / Guardian Decision	-	1	-	-	-	-	-	-	2	-	-	-	2	-	2	-

Baseline characteristics

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Reporting group title

10 mg QD

Reporting group description

MAK683 10 mg orally once daily

Reporting group title

20 mg QD

Reporting group description

MAK683 20 mg orally once daily

Reporting group title

40 mg QD

Reporting group description

MAK683 40 mg orally once daily

Reporting group title

80 mg QD

Reporting group description

MAK683 80 mg orally once daily

Reporting group title

120 mg QD

Reporting group description

MAK683 120 mg orally once daily

Reporting group title

160 mg QD

Reporting group description

MAK683 160 mg orally once daily

Reporting group title

240 mg QD

Reporting group description

MAK683 240 mg orally once daily

Reporting group title

300 mg QD

Reporting group description

MAK683 300 mg orally once daily

Reporting group title

500 mg QD

Reporting group description

MAK683 500 mg orally once daily

Reporting group title

800 mg QD

Reporting group description

MAK683 800 mg orally once daily

Reporting group title

60 mg BID

Reporting group description

MAK683 60 mg orally twice daily

Reporting group title

80 mg BID

Reporting group description

MAK683 80 mg orally twice daily

Reporting group title

120 mg BID

Reporting group description

MAK683 120 mg orally twice daily

Reporting group title

150 mg BID

Reporting group description

MAK683 150 mg orally twice daily

Reporting group title

300 mg BID

Reporting group description

MAK683 300 mg orally twice daily

Reporting group title

450 mg BID

Reporting group description

MAK683 450 mg orally twice daily

Reporting group values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID	Total
Number of subjects	4	7	3	8	8	5	6	4	18	4	8	11	11	8	30	4	139
Age Categorical
Units: participants
18 – <65 years	4	4	1	3	4	4	4	1	15	2	4	6	9	5	22	1	89
65 – <85 years	0	3	2	4	4	1	2	3	3	2	4	5	2	3	8	3	49
≥85 years	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1
Age continuous
Units: years
arithmetic mean (standard deviation)	54.0 ( 6.27 )	65.4 ( 8.64 )	60.3 ( 19.14 )	66.1 ( 16.33 )	60.4 ( 9.97 )	61.2 ( 7.50 )	59.0 ( 15.89 )	67.0 ( 9.09 )	46.4 ( 17.60 )	59.0 ( 13.98 )	61.8 ( 16.33 )	63.5 ( 9.75 )	51.6 ( 14.78 )	59.1 ( 13.46 )	54.0 ( 15.72 )	67.8 ( 9.91 )	-
Sex: Female, Male
Units: participants
Female	0	4	1	3	4	1	2	1	8	2	1	7	4	1	6	3	48
Male	4	3	2	5	4	4	4	3	10	2	7	4	7	7	24	1	91
Race/Ethnicity, Customized
Units: Subjects
Asian	2	3	2	3	4	1	0	0	6	1	1	1	3	3	5	1	36
Black	0	0	0	0	1	0	0	0	0	0	1	0	0	0	1	0	3
Caucasian	2	2	0	4	1	4	5	1	8	2	1	5	5	5	15	2	62
Other	0	0	1	1	2	0	1	3	3	0	5	5	2	0	3	0	26
Unknown	0	2	0	0	0	0	0	0	1	1	0	0	1	0	6	1	12
Disease classification
DLBCL - Diffuse large B-cell lymphoma. Solid tumors - including Nasopharyngeal carcinoma, gastric cancer, prostate cancer, ovarian cancer, sarcoma
Units: Subjects
DLBCL	1	3	1	3	4	0	2	2	1	1	5	5	1	1	1	0	31
Solid tumors	3	4	2	5	4	5	4	2	17	3	3	6	10	7	29	4	108

End points

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Reporting group title

10 mg QD

Reporting group description

MAK683 10 mg orally once daily

Reporting group title

20 mg QD

Reporting group description

MAK683 20 mg orally once daily

Reporting group title

40 mg QD

Reporting group description

MAK683 40 mg orally once daily

Reporting group title

80 mg QD

Reporting group description

MAK683 80 mg orally once daily

Reporting group title

120 mg QD

Reporting group description

MAK683 120 mg orally once daily

Reporting group title

160 mg QD

Reporting group description

MAK683 160 mg orally once daily

Reporting group title

240 mg QD

Reporting group description

MAK683 240 mg orally once daily

Reporting group title

300 mg QD

Reporting group description

MAK683 300 mg orally once daily

Reporting group title

500 mg QD

Reporting group description

MAK683 500 mg orally once daily

Reporting group title

800 mg QD

Reporting group description

MAK683 800 mg orally once daily

Reporting group title

60 mg BID

Reporting group description

MAK683 60 mg orally twice daily

Reporting group title

80 mg BID

Reporting group description

MAK683 80 mg orally twice daily

Reporting group title

120 mg BID

Reporting group description

MAK683 120 mg orally twice daily

Reporting group title

150 mg BID

Reporting group description

MAK683 150 mg orally twice daily

Reporting group title

300 mg BID

Reporting group description

MAK683 300 mg orally twice daily

Reporting group title

450 mg BID

Reporting group description

MAK683 450 mg orally twice daily

Primary: Incidence of dose limiting toxicities (DLTs)

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End point title

Incidence of dose limiting toxicities (DLTs) ^[1]

End point description

Number of participants with DLTS. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of continuous treatment with MAK683 and meets any of the protocol specified criteria.

End point type

Primary

End point timeframe

First cycle of treatment (28 days)

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 hypothesis testing was planned for this primary endpoint

End point values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	3	7	3	7	7	3	6	4	15	4	8	8	9	8	26	4
Units: participants	0	0	0	0	1	0	1	0	1	2	1	2	1	1	2	3

No statistical analyses for this end point

Primary: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

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End point title

Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) ^[2]

End point description

Number of participants with AEs and SAEs, including changes in laboratory values, vital signs and ECGs qualifying and reported as AEs.

End point type

Primary

End point timeframe

From first dose of study treatment until 30 days after last dose up to approximately 5.4 years

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical hypothesis testing was planned for this primary endpoint

End point values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	4	7	3	8	8	5	6	4	18	4	8	11	11	8	30	4
Units: participants
AEs	4	7	3	8	8	5	6	4	18	4	8	11	11	8	29	4
Treatment related AEs	4	4	3	3	4	2	2	3	14	4	8	5	9	7	22	4
SAEs	2	3	1	4	3	3	4	2	6	2	4	8	6	2	15	3
Treatment related SAEs	0	0	0	0	1	0	0	1	1	2	3	2	2	1	3	3
Fatal SAEs	0	0	0	0	0	0	3	0	1	0	1	2	0	1	1	1
AEs requiring additional therapy	4	7	2	7	6	4	6	3	16	4	7	11	10	7	25	4

No statistical analyses for this end point

Primary: Incidence of dose interruptions and dose reductions

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End point title

Incidence of dose interruptions and dose reductions ^[3]

End point description

Tolerability measured by the number of subjects who have interruptions or reductions of study treatment

End point type

Primary

End point timeframe

From first dose of study treatment until last dose up to approximately 5.3 years (average 57 days)

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 hypothesis testing was planned for this primary endpoint

End point values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	4	7	3	8	8	5	6	4	18	4	8	11	11	8	30	4
Units: participants
at least one dose reduction or interruption	2	3	1	6	4	3	3	3	12	4	7	10	6	4	19	4
at least one dose reduction	0	0	0	0	1	0	1	1	3	3	1	1	2	2	6	1
at least one dose interruption	2	3	1	6	4	3	3	3	12	4	7	10	5	4	19	4

No statistical analyses for this end point

Primary: Dose intensity

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End point title

Dose intensity ^[4]

End point description

Tolerability was measured by the dose of study drug. Dose intensity is defined as the ratio of actual dose received and actual duration of exposure.

End point type

Primary

End point timeframe

From first dose of study treatment until last dose up to approximately 5.3 years (average 57 days)

Notes
[4] - 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 hypothesis testing was planned for this primary endpoint

End point values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	4	7	3	8	8	5	6	4	18	4	8	11	11	8	30	4
Units: mg/day
arithmetic mean (standard deviation)	9.9 ( 0.12 )	21.1 ( 3.01 )	39.9 ( 0.16 )	76.1 ( 7.61 )	106.7 ( 23.10 )	154.8 ( 11.58 )	223.2 ( 35.79 )	269.4 ( 53.05 )	442.5 ( 99.40 )	485.1 ( 180.32 )	107.6 ( 17.42 )	150.0 ( 25.94 )	224.5 ( 44.96 )	278.4 ( 35.20 )	523.4 ( 121.93 )	723.3 ( 213.85 )

No statistical analyses for this end point

Primary: Relative Dose intensity

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End point title

Relative Dose intensity ^[5]

End point description

Tolerability was measured by the dose of study drug. Relative dose intensity is defined as the ratio of dose intensity to planned dose intensity multiplied by 100.

End point type

Primary

End point timeframe

From first dose of study treatment until last dose up to approximately 5.3 years (average 57 days)

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 hypothesis testing was planned for this primary endpoint

10 mg QD

20 mg QD

40 mg QD

80 mg QD

120 mg QD

160 mg QD

240 mg QD

300 mg QD

500 mg QD

800 mg QD

60 mg BID

80 mg BID

120 mg BID

150 mg BID

300 mg BID

450 mg BID

Number of subjects analysed

Units: percentage of planned dose intensity

median (full range (min-max))

100.0 (98 to 100)

100.0 (100 to 140)

100.0 (99 to 100)

100.0 (78 to 104)

100.0 (46 to 100)

100.0 (84 to 100)

100.0 (63 to 100)

97.9 (63 to 100)

99.7 (31 to 100)

62.7 (34 to 83)

96.6 (58 to 100)

98.5 (45 to 100)

100.0 (38 to 103)

99.4 (73 to 100)

100.0 (31 to 100)

84.7 (52 to 100)

No statistical analyses for this end point

Secondary: Overall Response Rate (ORR) - DLBCL

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End point title

Overall Response Rate (ORR) - DLBCL

End point description

Overall response rate (ORR) is the proportion of patients with a best overall response of CR or PR. Efficacy was based on local investigator assessment, as defined in Cheson 2014.

End point type

Secondary

End point timeframe

From first dose of study treatment until 30 days after last dose up to approximately 5.4 years

10 mg QD

20 mg QD

40 mg QD

80 mg QD

120 mg QD

160 mg QD

240 mg QD

300 mg QD

500 mg QD

800 mg QD

60 mg BID

80 mg BID

120 mg BID

150 mg BID

300 mg BID

450 mg BID

Number of subjects analysed

0 ^[6]

0 ^[7]

Units: Percentage of participants

number (confidence interval 90%)

0.0 (0.0 to 95.0)

33.3 (1.7 to 86.5)

0.0 (0.0 to 95.0)

0.0 (0.0 to 63.2)

0.0 (0.0 to 52.7)

( to )

0.0 (0.0 to 77.6)

0.0 (0.0 to 95.0)

40.0 (7.6 to 81.1)

20.0 (1.0 to 65.7)

0.0 (0.0 to 95.0)

( to )

Notes
[6] - No participants in this arm were analyzed for this endpoint
[7] - No participants in this arm were analyzed for this endpoint

No statistical analyses for this end point

Secondary: Overall Response Rate (ORR) - SOLID TUMORS

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End point title

Overall Response Rate (ORR) - SOLID TUMORS

End point description

Overall response rate (ORR) is the proportion of patients with a best overall response of CR or PR. Efficacy was based on based on local investigator assessment, as defined in Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

End point type

Secondary

End point timeframe

From first dose of study treatment until 30 days after last dose up to approximately 5.4 years

10 mg QD

20 mg QD

40 mg QD

80 mg QD

120 mg QD

160 mg QD

240 mg QD

300 mg QD

500 mg QD

800 mg QD

60 mg BID

80 mg BID

120 mg BID

150 mg BID

300 mg BID

450 mg BID

Number of subjects analysed

Units: Percentage of participants

number (confidence interval 90%)

0 (0.0 to 63.2)

0 (0.0 to 52.7)

0 (0.0 to 77.6)

0 (0.0 to 45.1)

0 (0.0 to 52.7)

0 (0.0 to 45.1)

0 (0.0 to 52.7)

0 (0.0 to 77.6)

5.9 (0.3 to 25.0)

0 (0.0 to 63.2)

0 (0.0 to 39.3)

20.0 (3.7 to 50.7)

0 (0.0 to 34.8)

0 (0.0 to 9.8)

0 (0.0 to 52.7)

No statistical analyses for this end point

Secondary: Best Overall Response (BOR) - DLBCL

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End point title

Best Overall Response (BOR) - DLBCL

End point description

The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. Efficacy was based on local investigator assessment, as defined in Cheson 2014.

End point type

Secondary

End point timeframe

From first dose of study treatment until 30 days after last dose up to approximately 5.4 years

End point values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	1	3	1	3	4	0 ^[8]	2	2	1	1	5	5	1	1	1	0 ^[9]
Units: participants
Complete Response (CR)	0	0	0	0	0		0	0	0	0	2	0	0	0	0
Partial Response (PR)	0	1	0	0	0		0	0	0	0	0	1	0	0	0
Stable Disease (SD)	0	0	1	0	1		0	0	0	0	1	0	0	1	1
Progressive Disease (PD)	1	2	0	2	2		2	2	1	1	1	3	1	0	0
Unknown (UNK)	0	0	0	1	1		0	0	0	0	1	1	0	0	0

Notes
[8] - No participants in this arm were analyzed for this endpoint
[9] - No participants in this arm were analyzed for this endpoint

No statistical analyses for this end point

Secondary: Best Overall Response (BOR) - SOLID TUMORS

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End point title

Best Overall Response (BOR) - SOLID TUMORS

End point description

The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. Efficacy was based on based on local investigator assessment, as defined in Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

End point type

Secondary

End point timeframe

From first dose of study treatment until 30 days after last dose up to approximately 5.4 years

End point values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	3	4	2	5	4	5	4	2	17	3	3	6	10	7	29	4
Units: participants
Partial Response (PR)	0	0	0	0	0	0	0	0	1	0	0	0	2	0	0	0
Stable Disease (SD)	0	1	1	3	0	1	1	0	9	1	3	1	2	5	10	1
Progressive Disease (PD)	1	2	1	1	4	3	2	2	4	2	0	2	5	2	16	1
Unknown (UNK)	2	1	0	1	0	1	1	0	3	0	0	3	1	0	3	2

No statistical analyses for this end point

Secondary: Duration of overall response (DOR) - DLBCL

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End point title

Duration of overall response (DOR) - DLBCL

End point description

The time between the date of first documented response (CR or PR) and the date of first documented progression or death. Duration of response was to be estimated using the Kaplan-Meier method. 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

From first time of CR/PR to date of death, treatment failure or relapse, up to approximately 5.4 years.

10 mg QD

20 mg QD

40 mg QD

80 mg QD

120 mg QD

160 mg QD

240 mg QD

300 mg QD

500 mg QD

800 mg QD

60 mg BID

80 mg BID

120 mg BID

150 mg BID

300 mg BID

450 mg BID

Number of subjects analysed

0 ^[10]

1 ^[11]

0 ^[12]

0 ^[13]

0 ^[14]

0 ^[15]

0 ^[16]

0 ^[17]

0 ^[18]

0 ^[19]

2 ^[20]

1 ^[21]

0 ^[22]

0 ^[23]

0 ^[24]

0 ^[25]

Units: months

median (confidence interval 90%)

( to )

3.7 (-999 to 999)

( to )

999 (999 to 999)

3.1 (-999 to 999)

( to )

Notes
[10] - No participants with CR or PR in this arm
[11] - NA: Not estimable due to insufficient number of participants with events
[12] - No participants with CR or PR in this arm
[13] - No participants with CR or PR in this arm
[14] - No participants with CR or PR in this arm
[15] - No participants with CR or PR in this arm
[16] - No participants with CR or PR in this arm
[17] - No participants with CR or PR in this arm
[18] - No participants with CR or PR in this arm
[19] - No participants with CR or PR in this arm
[20] - NA: Not estimable due to insufficient number of participants with events
[21] - NA: Not estimable due to insufficient number of participants with events
[22] - No participants with CR or PR in this arm
[23] - No participants with CR or PR in this arm
[24] - No participants with CR or PR in this arm
[25] - No participants with CR or PR in this arm

No statistical analyses for this end point

Secondary: Duration of overall response (DOR) - SOLID TUMORS

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End point title

Duration of overall response (DOR) - SOLID TUMORS

End point description

End point type

Secondary

End point timeframe

From first time of CR/PR to date of death, treatment failure or relapse, up to approximately 5.4 years.

10 mg QD

20 mg QD

40 mg QD

80 mg QD

120 mg QD

160 mg QD

240 mg QD

300 mg QD

500 mg QD

800 mg QD

60 mg BID

80 mg BID

120 mg BID

150 mg BID

300 mg BID

450 mg BID

Number of subjects analysed

0 ^[26]

0 ^[27]

0 ^[28]

0 ^[29]

0 ^[30]

0 ^[31]

0 ^[32]

0 ^[33]

1 ^[34]

0 ^[35]

0 ^[36]

0 ^[37]

2 ^[38]

0 ^[39]

0 ^[40]

0 ^[41]

Units: months

median (confidence interval 90%)

( to )

28.5 (-999 to 999)

( to )

999 (999 to 999)

( to )

Notes
[26] - No participants in this arm were analyzed for this endpoint
[27] - No participants in this arm were analyzed for this endpoint
[28] - No participants in this arm were analyzed for this endpoint
[29] - No participants in this arm were analyzed for this endpoint
[30] - No participants in this arm were analyzed for this endpoint
[31] - No participants in this arm were analyzed for this endpoint
[32] - No participants in this arm were analyzed for this endpoint
[33] - No participants in this arm were analyzed for this endpoint
[34] - NA: Not estimable due to insufficient number of participants with events
[35] - No participants in this arm were analyzed for this endpoint
[36] - No participants in this arm were analyzed for this endpoint
[37] - No participants in this arm were analyzed for this endpoint
[38] - NA: Not estimable due to insufficient number of participants with events
[39] - No participants in this arm were analyzed for this endpoint
[40] - No participants in this arm were analyzed for this endpoint
[41] - No participants in this arm were analyzed for this endpoint

No statistical analyses for this end point

Secondary: Progression-free survival (PFS) - DLBCL

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End point title

Progression-free survival (PFS) - DLBCL

End point description

Progression-free survival (PFS) is defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. 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

From first dose of study treatment to date of death, treatment failure or relapse, up to approximately 5.4 years

10 mg QD

20 mg QD

40 mg QD

80 mg QD

120 mg QD

160 mg QD

240 mg QD

300 mg QD

500 mg QD

800 mg QD

60 mg BID

80 mg BID

120 mg BID

150 mg BID

300 mg BID

450 mg BID

Number of subjects analysed

1 ^[42]

3 ^[43]

1 ^[44]

3 ^[45]

4 ^[46]

0 ^[47]

2 ^[48]

2 ^[49]

1 ^[50]

1 ^[51]

5 ^[52]

5 ^[53]

1 ^[54]

1 ^[55]

1 ^[56]

0 ^[57]

Units: months

median (confidence interval 90%)

2.4 (-999 to 999)

1.1 (1.0 to 999)

8.4 (-999 to 999)

0.9 (0.8 to 999)

1.8 (1.8 to 999)

( to )

2.0 (1.8 to 999)

1.9 (1.8 to 999)

0.9 (-999 to 999)

2.8 (-999 to 999)

7.5 (1.1 to 999)

1.1 (0.6 to 999)

0.9 (-999 to 999)

5.5 (-999 to 999)

4.1 (-999 to 999)

( to )

Notes
[42] - NA: Not estimable due to insufficient number of participants with events
[43] - NA: Not estimable due to insufficient number of participants with events
[44] - NA: Not estimable due to insufficient number of participants with events
[45] - NA: Not estimable due to insufficient number of participants with events
[46] - NA: Not estimable due to insufficient number of participants with events
[47] - No participants in this arm were analyzed for this endpoint
[48] - NA: Not estimable due to insufficient number of participants with events
[49] - NA: Not estimable due to insufficient number of participants with events
[50] - NA: Not estimable due to insufficient number of participants with events
[51] - NA: Not estimable due to insufficient number of participants with events
[52] - NA: Not estimable due to insufficient number of participants with events
[53] - NA: Not estimable due to insufficient number of participants with events
[54] - NA: Not estimable due to insufficient number of participants with events
[55] - NA: Not estimable due to insufficient number of participants with events
[56] - NA: Not estimable due to insufficient number of participants with events
[57] - No participants in this arm were analyzed for this endpoint

No statistical analyses for this end point

Secondary: Progression-free survival (PFS) - SOLID TUMORS

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End point title

Progression-free survival (PFS) - SOLID TUMORS

End point description

End point type

Secondary

End point timeframe

From first dose of study treatment to date of death, treatment failure or relapse, up to approximately 5.4 years

10 mg QD

20 mg QD

40 mg QD

80 mg QD

120 mg QD

160 mg QD

240 mg QD

300 mg QD

500 mg QD

800 mg QD

60 mg BID

80 mg BID

120 mg BID

150 mg BID

300 mg BID

450 mg BID

Number of subjects analysed

3 ^[58]

4 ^[59]

2 ^[60]

5 ^[61]

4 ^[62]

5 ^[63]

4 ^[64]

2 ^[65]

3 ^[66]

3 ^[67]

6 ^[68]

10 ^[69]

4 ^[70]

Units: months

median (confidence interval 90%)

1.6 (1.6 to 999)

1.8 (1.7 to 999)

2.7 (1.9 to 999)

3.9 (1.2 to 999)

1.7 (1.7 to 999)

1.9 (1.8 to 999)

1.1 (1.0 to 999)

1.8 (1.7 to 999)

3.6 (1.8 to 7.5)

2.0 (1.8 to 999)

10.5 (7.4 to 999)

1.8 (0.2 to 999)

1.6 (0.8 to 999)

3.7 (1.0 to 5.6)

1.9 (1.7 to 2.1)

1.7 (1.6 to 999)

Notes
[58] - NA: Not estimable due to insufficient number of participants with events
[59] - NA: Not estimable due to insufficient number of participants with events
[60] - NA: Not estimable due to insufficient number of participants with events
[61] - NA: Not estimable due to insufficient number of participants with events
[62] - NA: Not estimable due to insufficient number of participants with events
[63] - NA: Not estimable due to insufficient number of participants with events
[64] - NA: Not estimable due to insufficient number of participants with events
[65] - NA: Not estimable due to insufficient number of participants with events
[66] - NA: Not estimable due to insufficient number of participants with events
[67] - NA: Not estimable due to insufficient number of participants with events
[68] - NA: Not estimable due to insufficient number of participants with events
[69] - NA: Not estimable due to insufficient number of participants with events
[70] - NA: Not estimable due to insufficient number of participants with events

No statistical analyses for this end point

Secondary: Peak Plasma Concentration (Cmax) of MAK683

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End point title

Peak Plasma Concentration (Cmax) of MAK683

End point description

The maximum (peak) observed plasma, drug concentration after study drug administration (mass x volume-1). 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 day 8 and Cycle 2 day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose. 24 hour post-dose is collected for QD arms and a 12hour post-dose for BID arms.

End point values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	4	7	3	8	8	5	6	4	15	4	7	9	10	8	26	3 ^[71]
Units: ng/mL
arithmetic mean (standard deviation)
Cycle 1 day 1 n=4,7,3,8,8,5,6,4,15,4,7,9,10,5,25,3	70.9 ( 43.30 )	176 ( 108.00 )	337 ( 157.00 )	871 ( 548.00 )	659 ( 573.00 )	1380 ( 792.00 )	1920 ( 1690.00 )	3310 ( 949.00 )	3330 ( 2020.00 )	9470 ( 4250.00 )	518 ( 221.00 )	496 ( 411.00 )	973 ( 645.00 )	823 ( 514.00 )	1490 ( 1620 )	2880 ( 2280.00 )
Cycle 1 day 8 n= 4,7,3,8,7,4,5,3,13,4,5,9,9,8,26,3	67.4 ( 43.90 )	143 ( 87.60 )	333 ( 118.00 )	743 ( 516.00 )	943 ( 643.00 )	1560 ( 1330.00 )	1150 ( 861.00 )	3450 ( 1170.00 )	3120 ( 1940.00 )	10500 ( 3820.00 )	502 ( 224.00 )	622 ( 402.00 )	999 ( 579.00 )	1260 ( 851.00 )	2200 ( 1900.00 )	3400 ( 3220.00 )
Cycle 2 day 1 n= 3,5,3,5,6,4,4,4,9,2,6,5,5,6,20,0	71.4 ( 12.40 )	175 ( 54.30 )	239 ( 147.00 )	788 ( 355.00 )	995 ( 558.00 )	1620 ( 1150.00 )	1530 ( 755.00 )	2080 ( 1150.0 )	2380 ( 1810.00 )	4890 ( 127.00 )	669 ( 220.00 )	691 ( 324.00 )	575 ( 569.00 )	1340 ( 807.00 )	1510 ( 1380.00 )	999 ( 999 )

Notes
[71] - NA: Not aplicable due to 0 participants analyzed on Cycle 2 day 1

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration (AUClast) Time Curve of MAK683

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End point title

Area Under the Plasma Concentration (AUClast) Time Curve of MAK683

End point description

The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). 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 day 8 and Cycle 2 day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose. 24 hour post-dose is collected for QD arms and a 12hour post-dose for BID arms.

End point values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	4	7	3	8	8	5	6	4	15	4	7	9	10	8	26	3 ^[72]
Units: hours*ng/mL
arithmetic mean (standard deviation)
Cycle 1 day 1 n=4,7,3,8,8,5,6,4,15,4,7,9,10,5,25,3	326 ( 160.00 )	646 ( 254.00 )	2000 ( 977.00 )	3620 ( 1610.00 )	3700 ( 2670.00 )	5570 ( 2340.00 )	10100 ( 7080.00 )	13300 ( 5720.00 )	16300 ( 9570.00 )	52300 ( 33700.00 )	1520 ( 651.00 )	1650 ( 1310.00 )	3040 ( 1990.00 )	2630 ( 1760.00 )	4340 ( 4670.00 )	8720 ( 7370.00 )
Cycle 1 day 8 n=4,7,3,8,7,4,5,3,13,4,5,9,9,8,26,3	362 ( 79.10 )	583 ( 269.00 )	2130 ( 1200.00 )	4700 ( 2260.00 )	4390 ( 2160.00 )	6330 ( 3170.00 )	8440 ( 7270.00 )	19600 ( 10200.00 )	19400 ( 11800.00 )	77400 ( 43700.00 )	1830 ( 76700 )	2760 ( 2010.00 )	4360 ( 2210.00 )	4080 ( 1910.00 )	9700 ( 8860.00 )	20400 ( 20800.00 )
Cycle 2 day 1 n= 3,5,3,5,6,4,4,4,9,2,6,5,5,6,20,0	480 ( 102.00 )	796 ( 188.00 )	1560 ( 894.00 )	3900 ( 1190.00 )	5590 ( 3360.00 )	7960 ( 4530.00 )	9870 ( 3680.00 )	12300 ( 6900.00 )	14800 ( 10500.00 )	20200 ( 4690.00 )	2180 ( 841.00 )	2370 ( 1070.00 )	2130 ( 1850.00 )	3950 ( 1920.00 )	5200 ( 4050.00 )	999 ( 999 )

Notes
[72] - NA: Not aplicable due to 0 participants analyzed on Cycle 2 day 1

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration (AUCinf) Time Curve of MAK683

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End point title

Area Under the Plasma Concentration (AUCinf) Time Curve of MAK683

End point description

The AUC from time zero to infinity (mass x time x volume-1). 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 day 8 and Cycle 2 day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose. 24 hour post-dose is collected for QD arms and a 12hour post-dose for BID arms.

End point values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	3	6	3	8	7	5	6	4	14	4	6	7	7 ^[73]	8 ^[74]	14	2 ^[75]
Units: hours*ng/mL
arithmetic mean (standard deviation)
Cycle 1 day 1 n=3,6,3,8,7,5,5,4,14,4,4,6,7,4,12,2	417 ( 79.60 )	733 ( 184.00 )	2060 ( 1030.00 )	3700 ( 1670.00 )	3280 ( 2450.00 )	5750 ( 2210.00 )	10700 ( 7940.00 )	13600 ( 6030.00 )	16500 ( 9980.00 )	53800 ( 35900.00 )	1820 ( 708.00 )	2330 ( 1670.00 )	4330 ( 2310.00 )	3760 ( 1700.00 )	6910 ( 4040.00 )	15100 ( 4220.00 )
Cycle 1 day 8 n= 3,6,3,5,6,3,3,3,13,4,4,7,6,8,14,2	398 ( 62.00 )	684 ( 144.00 )	2200 ( 1260.00 )	4620 ( 2160.00 )	4660 ( 2350.00 )	6030 ( 3720.00 )	7740 ( 6420.00 )	20600 ( 11700.00 )	19900 ( 12100.00 )	81000 ( 47000.00 )	2290 ( 569.00 )	2500 ( 1190.00 )	4390 ( 2900.00 )	4440 ( 2040.00 )	10800 ( 4380.00 )	35100 ( 21000.00 )
cycle 2 day 1 n=2,4,3,5,6,4,3,4,9,2,2,4,1,1,7,0	430 ( 24.80 )	721 ( 14.10 )	1640 ( 909.00 )	4020 ( 1310.00 )	5710 ( 3490.00 )	8090 ( 4520.00 )	10200 ( 4720.00 )	12600 ( 7150.00 )	15100 ( 10800.00 )	20900 ( 5250.00 )	1330 ( 86.40 )	3110 ( 923.00 )	3650 ( 999 )	4560 ( 999 )	7880 ( 5090.00 )	999 ( 999 )

Notes
[73] - NA: Not estimable due to insufficient number of participants
[74] - NA: Not estimable due to insufficient number of participants
[75] - NA: Not aplicable due to 0 participants analyzed on Cycle 2 day 1

No statistical analyses for this end point

Secondary: Time to Peak Plasma Concentration (Tmax) of MAK683

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End point title

Time to Peak Plasma Concentration (Tmax) of MAK683

End point description

The time to reach maximum (peak) plasma drug concentration after study drug administration (time). 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 day 8 and Cycle 2 day 1: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose. 24 hour post-dose is collected for QD arms and a 12hour post-dose for BID arms.

10 mg QD

20 mg QD

40 mg QD

80 mg QD

120 mg QD

160 mg QD

240 mg QD

300 mg QD

500 mg QD

800 mg QD

60 mg BID

80 mg BID

120 mg BID

150 mg BID

300 mg BID

450 mg BID

Number of subjects analysed

3 ^[76]

Units: hours

median (full range (min-max))

Cycle 1 day 1 n=4,7,3,8,8,5,6,4,15,4,7,9,10,5,25,3

1.07 (0.917 to 7.03)

2.08 (0.5 to 3)

1.05 (0.983 to 3)

1 (0.5 to 3.03)

1.05 (0.567 to 8.05)

1 (0.583 to 2)

3.23 (1 to 6.17)

1 (0.567 to 1.02)

2 (0.983 to 3.85)

1.52 (0.817 to 2.17)

1 (0.617 to 4)

1.08 (0.5 to 4)

1.08 (0.5 to 2.03)

1.82 (0.9 to 2.08)

2.08 (0.5 to 8.02)

1.17 (0.417 to 8.02)

Cycle 1 day 8 n= 4,7,3,8,7,4,5,3,13,4,5,9,9,8,26,3

1.6 (1 to 5.5)

1.08 (0.467 to 2.02)

2 (2 to 2.03)

0.975 (0.5 to 7)

1 (0.583 to 5.97)

1.08 (0.583 to 1.93)

4.08 (0.5 to 6.08)

2 (0.5 to 2.15)

2.13 (0.75 to 4.05)

1.33 (0.95 to 1.98)

1.05 (0.5 to 2)

2 (0.517 to 3.5)

1.12 (0 to 6)

1.05 (0.4 to 2.8)

1.99 (0 to 7.92)

1.08 (0.5 to 2.92)

cycle 2 day 1 n= 3,5,3,5,6,4,4,4,9,2,6,5,5,6,20,0

2.15 (2 to 5.45)

1 (0.5 to 7.77)

2.97 (1 to 3)

1.03 (0.5 to 3.03)

2.03 (0.417 to 3)

1.08 (1.08 to 2)

2 (0.583 to 3.93)

2.07 (1.03 to 3.92)

1.98 (0.833 to 3.83)

0.867 (0.583 to 1.15)

1 (0 to 2.03)

1.18 (0.833 to 4)

1.95 (1.12 to 2.98)

1.07 (0.4 to 2)

2.08 (0 to 6.05)

999 (999 to 999)

Notes
[76] - NA: Not aplicable due to 0 participants analyzed on Cycle 2 day 1

No statistical analyses for this end point

Secondary: Change from baseline H3K27 tri methylation level in PBMC

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End point title

Change from baseline H3K27 tri methylation level in PBMC ^[77]

End point description

Best percent change from baseline for H3K12 trimethylation in peripheral blood mononuclear cell (PBMC). Where "Best percent change from baseline" is defined as maximum reduction from baseline at any on-treatment time point. Different cell populations were evaluated. 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 1,8 and 15, Cycle 2 Day 1, Cycle 3 Day 1

Notes
[77] - 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: Change in H3K27 trimethylation in PBMC was only assessed in subsets of participants treated with ≥ 500 mg QD and the entire BID dose range of MAK683 evaluated.

End point values	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	8	3 ^[78]	2 ^[79]	3 ^[80]	4	6	16	2 ^[81]
Units: Percent change in H3K27 trimethylation
arithmetic mean (standard deviation)
CD19+ population n= 7,2,,2,1,3,3,11,1	-57.6 ( 29.36 )	-58 ( 22.27 )	-88.6 ( 3.68 )	-38 ( 999 )	-63.9 ( 23.33 )	-66.1 ( 22.84 )	-46.1 ( 25.08 )	-16.3 ( 999 )
CD3+ population n= 5,1,1,1,3,4,12,0	-61.5 ( 37.42 )	-34.4 ( 999 )	-31.9 ( 999 )	-88.7 ( 999 )	-44 ( 46.46 )	-26.8 ( 24.28 )	-50.4 ( 28.50 )	999 ( 999 )
HLADR+CD14+ population n=8,3,2,3,4,6,16,2	-87 ( 9.35 )	-80.9 ( 27.22 )	-78.3 ( 2.19 )	-89.8 ( 16.43 )	-84.4 ( 10.67 )	-77.7 ( 24.19 )	-79.7 ( 17.69 )	-84.3 ( 13.15 )

Notes
[78] - NA: Not aplicable due to single participant analyzed for CD3+
[79] - NA: Not aplicable due to single participant analyzed for CD3+
[80] - NA: Not aplicable due to single participant analyzed for CD3+
[81] - NA: Not aplicable due to single participant analyzed for CD19+ and 0 participants for CD3+

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 deaths were collected from first dose of study treatment to 30 days after last dose. Post- treatment and disease progression FU deaths were collected from 31 days after last dose until end of study. All deaths refer to the sum of pre-treatment deaths, on-treatment, post-treatment safety FU deaths, and disease progression FU deaths.

End point type

Post-hoc

End point timeframe

On-treatment deaths: up to approximately 5.4 years. Post-treatment safety FU and disease progression FU deaths: up to 5.4 years

End point values	10 mg QD	20 mg QD	40 mg QD	80 mg QD	120 mg QD	160 mg QD	240 mg QD	300 mg QD	500 mg QD	800 mg QD	60 mg BID	80 mg BID	120 mg BID	150 mg BID	300 mg BID	450 mg BID
Number of subjects analysed	4	7	3	8	8	5	6	4	18	4	8	11	11	8	30	4
Units: participants
On treatment deaths	0	1	0	0	0	0	3	0	1	0	0	3	1	1	2	0
Post-treatment death	3	1	0	1	2	0	0	1	1	0	1	3	2	1	7	2
Total deaths	3	2	0	1	2	0	3	1	2	0	1	6	3	2	9	2

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

On treatment Adverse events and deaths : from first dose of study treatment until 30 days after last treatment up to maximum duration of 5.4 years

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

27.1

Reporting group title

Phase I 40 mg QD fasted

Reporting group description

Phase I 40 mg QD fasted

Reporting group title

Phase I 20 mg QD fasted

Reporting group description

Phase I 20 mg QD fasted

Reporting group title

Phase I 10 mg QD fasted

Reporting group description

Phase I 10 mg QD fasted

Reporting group title

Phase I 240 mg QD fasted

Reporting group description

Phase I 240 mg QD fasted

Reporting group title

Phase I 450 mg BID fasted

Reporting group description

Phase I 450 mg BID fasted

Reporting group title

Phase I 500 mg QD fasted

Reporting group description

Phase I 500 mg QD fasted

Reporting group title

Phase I 800 mg QD fasted

Reporting group description

Phase I 800 mg QD fasted

Reporting group title

Phase I 60 mg BID fasted

Reporting group description

Phase I 60 mg BID fasted

Reporting group title

Phase I 80 mg BID fasted

Reporting group description

Phase I 80 mg BID fasted

Reporting group title

Phase I 120 mg BID fasted

Reporting group description

Phase I 120 mg BID fasted

Reporting group title

Phase I 150 mg BID fasted

Reporting group description

Phase I 150 mg BID fasted

Reporting group title

Phase I 300 mg BID fasted

Reporting group description

Phase I 300 mg BID fasted

Reporting group title

Phase I 160 mg QD fasted

Reporting group description

Phase I 160 mg QD fasted

Reporting group title

Phase I 120 mg QD fasted

Reporting group description

Phase I 120 mg QD fasted

Reporting group title

Phase I 80 mg QD fasted

Reporting group description

Phase I 80 mg QD fasted

Reporting group title

Phase I 300 mg QD fasted

Reporting group description

Phase I 300 mg QD fasted

Phase I 40 mg QD fasted

Phase I 20 mg QD fasted

Phase I 10 mg QD fasted

Phase I 240 mg QD fasted

Phase I 450 mg BID fasted

Phase I 500 mg QD fasted

Phase I 800 mg QD fasted

Phase I 60 mg BID fasted

Phase I 80 mg BID fasted

Phase I 120 mg BID fasted

Phase I 150 mg BID fasted

Phase I 300 mg BID fasted

Phase I 160 mg QD fasted

Phase I 120 mg QD fasted

Phase I 80 mg QD fasted

Phase I 300 mg QD fasted

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 3 (33.33%)

3 / 7 (42.86%)

2 / 4 (50.00%)

4 / 6 (66.67%)

3 / 4 (75.00%)

6 / 18 (33.33%)

2 / 4 (50.00%)

4 / 8 (50.00%)

8 / 11 (72.73%)

6 / 11 (54.55%)

2 / 8 (25.00%)

15 / 30 (50.00%)

3 / 5 (60.00%)

3 / 8 (37.50%)

4 / 8 (50.00%)

2 / 4 (50.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Cancer pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Leukaemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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

Lymphangiosis carcinomatosa

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant neoplasm progression

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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

Malignant pleural effusion

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 18 (5.56%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metastatic neoplasm

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour associated fever

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 18 (5.56%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Vascular disorders

Arterial haemorrhage

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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

General disorders and administration site conditions

Condition aggravated

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fatigue

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General physical health deterioration

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

1 / 4 (25.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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

Multiple organ dysfunction syndrome

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 11 (9.09%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Pyrexia

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 18 (5.56%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

1 / 5 (20.00%)

0 / 8 (0.00%)

2 / 8 (25.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

1 / 11 (9.09%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Epistaxis

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 11 (9.09%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory failure

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Confusional state

subjects affected / exposed

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 4 (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

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 4 (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

Neutrophil count decreased

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Platelet count decreased

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 11 (9.09%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Red blood cell morphology abnormal

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Clavicle fracture

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

1 / 11 (9.09%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular access complication

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 18 (5.56%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Left ventricular dysfunction

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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

Bell's palsy

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

1 / 11 (9.09%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Presyncope

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 4 (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 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal cord compression

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

2 / 4 (50.00%)

0 / 18 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 4 (25.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

2 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

2 / 2

deaths causally related to treatment / all

0 / 0

Febrile neutropenia

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

1 / 11 (9.09%)

0 / 8 (0.00%)

2 / 30 (6.67%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenia

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Thrombocytopenia

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 18 (0.00%)

1 / 4 (25.00%)

1 / 8 (12.50%)

2 / 11 (18.18%)

1 / 11 (9.09%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

2 / 3

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal pain upper

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 11 (9.09%)

0 / 11 (0.00%)

0 / 8 (0.00%)

2 / 30 (6.67%)

1 / 5 (20.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 11 (9.09%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileus

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 11 (9.09%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 11 (9.09%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Obstruction gastric

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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

Oesophageal stenosis

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancreatitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 4 (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 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Upper gastrointestinal haemorrhage

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

1 / 5 (20.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Cholestasis

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hydronephrosis

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haematuria

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal failure

subjects affected / exposed

1 / 3 (33.33%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Musculoskeletal and connective tissue disorders

Back pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 4 (25.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Bone pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 11 (9.09%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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

COVID-19

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumocystis jirovecii pneumonia

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 18 (5.56%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

1 / 11 (9.09%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 18 (5.56%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 11 (9.09%)

0 / 11 (0.00%)

2 / 8 (25.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Pneumonia mycoplasmal

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 18 (5.56%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia pneumococcal

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Postoperative wound infection

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 18 (5.56%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory tract infection

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Salmonella bacteraemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

1 / 11 (9.09%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

1 / 30 (3.33%)

0 / 5 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 4 (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 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 11 (9.09%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sinusitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Staphylococcal bacteraemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Suspected COVID-19

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

1 / 8 (12.50%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

0 / 4 (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

Dehydration

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyponatraemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 18 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 11 (0.00%)

1 / 11 (9.09%)

0 / 8 (0.00%)

0 / 30 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

0 / 4 (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	Phase I 40 mg QD fasted	Phase I 20 mg QD fasted	Phase I 10 mg QD fasted	Phase I 240 mg QD fasted	Phase I 450 mg BID fasted	Phase I 500 mg QD fasted	Phase I 800 mg QD fasted	Phase I 60 mg BID fasted	Phase I 80 mg BID fasted	Phase I 120 mg BID fasted	Phase I 150 mg BID fasted	Phase I 300 mg BID fasted	Phase I 160 mg QD fasted	Phase I 120 mg QD fasted	Phase I 80 mg QD fasted	Phase I 300 mg QD fasted
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	6 / 7 (85.71%)	4 / 4 (100.00%)	6 / 6 (100.00%)	4 / 4 (100.00%)	18 / 18 (100.00%)	4 / 4 (100.00%)	8 / 8 (100.00%)	11 / 11 (100.00%)	11 / 11 (100.00%)	8 / 8 (100.00%)	29 / 30 (96.67%)	5 / 5 (100.00%)	8 / 8 (100.00%)	8 / 8 (100.00%)	4 / 4 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Tumour associated fever
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Tumour haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Tumour pain
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 18 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	3 / 11 (27.27%)	1 / 11 (9.09%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	2	0	0	3	1	1	0	0	0	1	0
Vascular disorders
Flushing
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0
Hypertension
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Subclavian vein thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Peripheral coldness
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Pallor
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hypotension
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Venous thrombosis limb
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Chronic fatigue syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Chills
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	0	0	0	1	0	0	0	0	0	0	1	0	0
Asthenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	2 / 18 (11.11%)	0 / 4 (0.00%)	2 / 8 (25.00%)	2 / 11 (18.18%)	2 / 11 (18.18%)	2 / 8 (25.00%)	4 / 30 (13.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 4 (25.00%)
occurrences all number	0	0	0	2	1	2	0	4	2	2	2	6	0	0	1	1
Early satiety
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0
Fatigue
subjects affected / exposed	1 / 3 (33.33%)	2 / 7 (28.57%)	3 / 4 (75.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 18 (11.11%)	2 / 4 (50.00%)	1 / 8 (12.50%)	1 / 11 (9.09%)	4 / 11 (36.36%)	0 / 8 (0.00%)	5 / 30 (16.67%)	1 / 5 (20.00%)	2 / 8 (25.00%)	2 / 8 (25.00%)	0 / 4 (0.00%)
occurrences all number	1	2	3	0	1	2	2	1	1	4	0	5	1	2	2	0
Gait disturbance
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
General physical health deterioration
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Hyperthermia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Face oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Facial pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Localised oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Mucosal inflammation
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	1	0	0	1	0	0	0	1	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0
Oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Influenza like illness
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Oedema peripheral
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 11 (18.18%)	1 / 11 (9.09%)	0 / 8 (0.00%)	3 / 30 (10.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	1	0	0	0	2	1	0	3	0	0	1	1
Swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Supraclavicular fossa pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	4 / 18 (22.22%)	0 / 4 (0.00%)	3 / 8 (37.50%)	3 / 11 (27.27%)	3 / 11 (27.27%)	4 / 8 (50.00%)	5 / 30 (16.67%)	0 / 5 (0.00%)	2 / 8 (25.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	2	4	0	6	3	4	5	5	0	4	0	1
Peripheral swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 30 (3.33%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	1	0	1	0	0
Swelling face
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Temperature regulation disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Xerosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 18 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0
Reproductive system and breast disorders
Amenorrhoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Pelvic pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Penile oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Aspiration
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Cough
subjects affected / exposed	0 / 3 (0.00%)	2 / 7 (28.57%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	5 / 18 (27.78%)	0 / 4 (0.00%)	3 / 8 (37.50%)	0 / 11 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	3 / 30 (10.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	1	0	0	5	0	4	0	2	1	3	0	1	0	0
Dysphonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	2	0	0	0	1	0	0	0	0
Haemoptysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	3	0	0	0	0
Dyspnoea
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	1 / 8 (12.50%)	2 / 30 (6.67%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	1	1	2	0	1	1	1
Hiccups
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Nasal congestion
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 18 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	1	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0
Pleural effusion
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	2 / 11 (18.18%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	2	0	1	0	0	1	0
Pneumonitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0
Hypoxia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Lung infiltration
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Productive cough
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	0	1	0	1	0	0
Pulmonary embolism
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Pulmonary tumour thrombotic microangiopathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Respiratory failure
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0
Wheezing
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	1	0	0	0	0	0
Depression
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Depressive symptom
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Fear of eating
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Insomnia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 11 (18.18%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 30 (3.33%)	1 / 5 (20.00%)	2 / 8 (25.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	2	0	1	1	1	2	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	3 / 30 (10.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	1	1	3	0	0	1	0
Amylase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	3	0	1	0	0	0	0	0	2	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	2 / 11 (18.18%)	2 / 8 (25.00%)	4 / 30 (13.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	2 / 8 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	3	1	0	2	2	4	0	0	2	0
Blood albumin decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	3	0	0	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 18 (5.56%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	1 / 8 (12.50%)	4 / 30 (13.33%)	1 / 5 (20.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	1	1	0	1	1	1	4	1	0	1	0
Blood bilirubin increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	1	0	1	1	0	0	0	0
Blood magnesium decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	2	0	0	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Blood creatinine increased
subjects affected / exposed	1 / 3 (33.33%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	2 / 18 (11.11%)	2 / 4 (50.00%)	0 / 8 (0.00%)	2 / 11 (18.18%)	2 / 11 (18.18%)	1 / 8 (12.50%)	3 / 30 (10.00%)	0 / 5 (0.00%)	2 / 8 (25.00%)	2 / 8 (25.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	2	0	3	2	0	2	2	1	4	0	2	2	0
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	1	1	0	1	0	2	0	1	0	1	1	0
Blood creatine increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Blood calcium decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Blood phosphorus decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Blood sodium increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Blood uric acid increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
C-reactive protein increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 18 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	1 / 8 (12.50%)	6 / 30 (20.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	2	0	0	1	0	1	8	0	0	1	0
Protein total decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	2	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	1 / 18 (5.56%)	2 / 4 (50.00%)	0 / 8 (0.00%)	3 / 11 (27.27%)	0 / 11 (0.00%)	4 / 8 (50.00%)	5 / 30 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	2	3	4	0	3	0	5	6	0	0	1	0
Neutrophil count decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	3 / 18 (16.67%)	1 / 4 (25.00%)	2 / 8 (25.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	2 / 30 (6.67%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	2	1	27	3	2	0	1	3	2	0	1	1	0
Lymphocyte count decreased
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 18 (11.11%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	2 / 11 (18.18%)	1 / 8 (12.50%)	3 / 30 (10.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	4	1	0	0	2	1	3	0	0	1	0
Lipase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	3 / 30 (10.00%)	2 / 5 (40.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1	5	3	0	0	0
Hepatic enzyme abnormal
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
SARS-CoV-2 test negative
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	2 / 8 (25.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	2	4	0	0	0	0	0
Vitamin D decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
SARS-CoV-2 test positive
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 18 (11.11%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	5 / 30 (16.67%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	1	2	0	1	0	1	0	5	0	1	1	0
White blood cell count decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	4 / 18 (22.22%)	1 / 4 (25.00%)	1 / 8 (12.50%)	1 / 11 (9.09%)	2 / 11 (18.18%)	1 / 8 (12.50%)	5 / 30 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	23	1	1	1	4	1	6	0	0	0	0
Injury, poisoning and procedural complications
Clavicle fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Contusion
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Eye contusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Fall
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0
Post procedural haematoma
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Procedural pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	0	1	1	0	0	0
Radiation skin injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Transfusion reaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Skin laceration
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Vascular access complication
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Cardiac disorders
Tricuspid valve disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	2	0	0	0	1	1	0
Supraventricular extrasystoles
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Sinus bradycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Pericardial effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Mitral valve thickening
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Nervous system disorders
Bell's palsy
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Dizziness
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	1	0
Drooling
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Neuralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Myoclonus
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Headache
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	1 / 11 (9.09%)	2 / 11 (18.18%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	2 / 8 (25.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	1	1	1	3	0	2	0	3	0	0
Febrile convulsion
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Dysgeusia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	1	0	1	0	1	0	0	3	0	0	1	0
Neuropathy peripheral
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 18 (16.67%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	3	0	1	0	0	0	1	0	0	0	1
Peripheral motor neuropathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Sciatica
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Presyncope
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0
Taste disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	2	0	0	1	0	0	0	0	0	0
Transient ischaemic attack
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
VIth nerve paralysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	3 / 18 (16.67%)	2 / 4 (50.00%)	5 / 8 (62.50%)	1 / 11 (9.09%)	3 / 11 (27.27%)	1 / 8 (12.50%)	6 / 30 (20.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	2 / 4 (50.00%)
occurrences all number	1	1	0	1	4	3	3	5	2	16	1	10	0	1	0	4
Anaemia
subjects affected / exposed	1 / 3 (33.33%)	2 / 7 (28.57%)	1 / 4 (25.00%)	1 / 6 (16.67%)	3 / 4 (75.00%)	6 / 18 (33.33%)	3 / 4 (75.00%)	1 / 8 (12.50%)	3 / 11 (27.27%)	4 / 11 (36.36%)	0 / 8 (0.00%)	15 / 30 (50.00%)	1 / 5 (20.00%)	2 / 8 (25.00%)	1 / 8 (12.50%)	2 / 4 (50.00%)
occurrences all number	2	2	1	1	3	7	5	1	3	9	0	19	1	2	1	4
Iron deficiency anaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Leukopenia
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	4	0	0	1	0	0	0	1	0	0	0	1
Lymphopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	2 / 8 (25.00%)	3 / 11 (27.27%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	1	0	2	3	0	0	0	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 4 (75.00%)	2 / 18 (11.11%)	2 / 4 (50.00%)	4 / 8 (50.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	6 / 30 (20.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	3 / 4 (75.00%)
occurrences all number	0	0	0	0	5	5	2	5	0	9	0	14	0	1	0	5
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
External ear inflammation
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hypoacusis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Middle ear effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Eye disorders
Blepharitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Dry eye
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Eye oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Glaucoma
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Papilloedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Vision blurred
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Uveitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Retinopathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Periorbital oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Abdominal distension
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	2	0	0	0	0
Abdominal rigidity
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Abdominal pain upper
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	1	1	0	1	0	0	0	0
Abdominal pain
subjects affected / exposed	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	1 / 11 (9.09%)	2 / 11 (18.18%)	0 / 8 (0.00%)	3 / 30 (10.00%)	2 / 5 (40.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	2	0	2	0	0	1	1	1	3	0	3	2	0	1	0
Angular cheilitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Ascites
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0
Constipation
subjects affected / exposed	0 / 3 (0.00%)	2 / 7 (28.57%)	1 / 4 (25.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	4 / 18 (22.22%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	2 / 11 (18.18%)	0 / 8 (0.00%)	4 / 30 (13.33%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	1	2	1	4	1	0	1	2	0	6	1	0	0	0
Dental caries
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 18 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0
Dental discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Diarrhoea
subjects affected / exposed	0 / 3 (0.00%)	2 / 7 (28.57%)	1 / 4 (25.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	4 / 18 (22.22%)	3 / 4 (75.00%)	3 / 8 (37.50%)	2 / 11 (18.18%)	2 / 11 (18.18%)	3 / 8 (37.50%)	12 / 30 (40.00%)	1 / 5 (20.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)	1 / 4 (25.00%)
occurrences all number	0	2	2	1	1	5	3	3	2	2	4	16	1	1	1	2
Dry mouth
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dyspepsia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	1	0	1	0	0
Dysphagia
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	2 / 8 (25.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	1	0	0	0	2	1	0	0	1	0	2	0	0
Gingival bleeding
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	0 / 8 (0.00%)	3 / 30 (10.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	3	0	0	0	0
Gastric ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Haemorrhoids
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Intestinal stenosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Inguinal hernia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Ileus
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	0 / 3 (0.00%)	3 / 7 (42.86%)	1 / 4 (25.00%)	3 / 6 (50.00%)	2 / 4 (50.00%)	8 / 18 (44.44%)	3 / 4 (75.00%)	1 / 8 (12.50%)	2 / 11 (18.18%)	3 / 11 (27.27%)	3 / 8 (37.50%)	11 / 30 (36.67%)	3 / 5 (60.00%)	1 / 8 (12.50%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	3	2	4	2	9	6	1	3	3	5	12	3	2	1	0
Odynophagia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0
Oesophagitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0
Rectal haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	1	0	1	0	0	0	0
Tooth loss
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0
Vomiting
subjects affected / exposed	0 / 3 (0.00%)	2 / 7 (28.57%)	2 / 4 (50.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	7 / 18 (38.89%)	2 / 4 (50.00%)	1 / 8 (12.50%)	3 / 11 (27.27%)	2 / 11 (18.18%)	0 / 8 (0.00%)	10 / 30 (33.33%)	1 / 5 (20.00%)	2 / 8 (25.00%)	1 / 8 (12.50%)	1 / 4 (25.00%)
occurrences all number	0	2	3	3	1	7	3	1	3	3	0	11	1	2	1	1
Hepatobiliary disorders
Cholestasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hepatic cytolysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0
Hepatic vein thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hyperbilirubinaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Jaundice
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 18 (11.11%)	2 / 4 (50.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	3 / 11 (27.27%)	0 / 8 (0.00%)	3 / 30 (10.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	2	2	0	0	3	0	5	0	0	1	0
Dermatitis allergic
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Dry skin
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	2	0	0	1	0
Eczema
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Hyperhidrosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	1
Night sweats
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Petechiae
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Rash maculo-papular
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Rash
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	6 / 18 (33.33%)	1 / 4 (25.00%)	2 / 8 (25.00%)	0 / 11 (0.00%)	3 / 11 (27.27%)	1 / 8 (12.50%)	3 / 30 (10.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	8	1	3	0	3	1	3	0	0	0	0
Pruritus
subjects affected / exposed	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	1	1	0	0	0	1	0	2	0	0	1	0
Prurigo
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Rash papular
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Rash pruritic
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Skin erosion
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Skin exfoliation
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	3 / 30 (10.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	3	0	0	0	0
Nocturia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Haematuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	2 / 5 (40.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	2	0	0	0	2	0	1	0
Pollakiuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Urine flow decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Renal impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Renal failure
subjects affected / exposed	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hypopituitarism
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hypothyroidism
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	1	0	0	1	0	1	0	0
Back pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	2 / 4 (50.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	4 / 18 (22.22%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	2 / 30 (6.67%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	2	1	0	4	0	1	0	1	0	2	1	0	0	1
Musculoskeletal chest pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0
Muscular weakness
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0
Groin pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Bone pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	1	1	0	0	0	0	0	0
Myalgia
subjects affected / exposed	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0
Neck pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	1	0
Pain in extremity
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 11 (9.09%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	1	0	1	1	1	0	1	0	0	0	0
Spinal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0
Synovitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Temporomandibular pain and dysfunction syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Infections and infestations
Abdominal infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Bronchitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	2	0	0	0	0
Bronchitis viral
subjects affected / exposed	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
COVID-19
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 18 (11.11%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	0	3	0	1	1	1	0	0	0	0
Gingivitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0
Folliculitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Ear infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Cellulitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	2	0	0	0	0	0	1	0
Candida infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Herpes ophthalmic
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Lower respiratory tract infection bacterial
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Influenza
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Oral candidiasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	1	0	0	0	1	0	0
Oral fungal infection
subjects affected / exposed	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Oral viral infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Periodontitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Peritonsillar abscess
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Pharyngitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	2	0	0	0	0	0	1
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Septic shock
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory tract infection viral
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	5	0	0	1	1	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0	0	0	0	1	0
Tooth infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0
Soft tissue infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	2	0	1	0	0
Urinary tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	1 / 11 (9.09%)	0 / 8 (0.00%)	0 / 30 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	1	0	0	1	0	2	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Cell death
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Decreased appetite
subjects affected / exposed	0 / 3 (0.00%)	4 / 7 (57.14%)	2 / 4 (50.00%)	2 / 6 (33.33%)	2 / 4 (50.00%)	2 / 18 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 11 (18.18%)	4 / 11 (36.36%)	1 / 8 (12.50%)	9 / 30 (30.00%)	2 / 5 (40.00%)	0 / 8 (0.00%)	3 / 8 (37.50%)	0 / 4 (0.00%)
occurrences all number	0	4	2	3	2	2	0	0	2	4	1	11	2	0	3	0
Fluid retention
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0	0
Dehydration
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	3 / 11 (27.27%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	3	0	3	0	0	0	0
Hyperamylasaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hyperglycaemia
subjects affected / exposed	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0
Hypercholesterolaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	1	0	0	0	0
Hypercalcaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	0 / 8 (0.00%)	1 / 30 (3.33%)	1 / 5 (20.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	2	2	2	0	0
Hyperkalaemia
subjects affected / exposed	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypernatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hypochloraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	1 / 8 (12.50%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hypocalcaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	2 / 30 (6.67%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	1	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 18 (5.56%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	1 / 30 (3.33%)	0 / 5 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	1	2	0	0	0	0	0	1	0	0	2	0
Hypoglycaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 11 (9.09%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hypokalaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	3 / 11 (27.27%)	2 / 8 (25.00%)	6 / 30 (20.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	4	4	6	0	2	0	0
Hypomagnesaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 18 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	1 / 11 (9.09%)	1 / 11 (9.09%)	3 / 8 (37.50%)	3 / 30 (10.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0	1	1	1	1	4	3	0	0	0	0
Hyponatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 18 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	1 / 11 (9.09%)	1 / 8 (12.50%)	2 / 30 (6.67%)	1 / 5 (20.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	1	1	2	1	0	1	0
Hypophosphataemia
subjects affected / exposed	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 18 (5.56%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 11 (0.00%)	0 / 11 (0.00%)	2 / 8 (25.00%)	3 / 30 (10.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)	2 / 8 (25.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	1	0	1	1	0	0	0	2	3	0	3	2	0
Vitamin D deficiency
subjects affected / exposed	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 18 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 11 (0.00%)	0 / 11 (0.00%)	0 / 8 (0.00%)	0 / 30 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

19 Jul 2016

• To modify the inclusion criteria to include only participants who had exhausted all options and for whom no standard therapy exists. • To update the DLT criteria for gastrointestinal toxicity and thrombocytopenia toxicity.

31 Aug 2017

The primary purpose of this amendment was to specify the clinical indications to be enrolled in this study.

27 Jun 2018

The primary purpose of this amendment was to add clinical indications to be investigated in the Phase II part. In addition, several study assessments have been modified in this amendment: • The PBMC sample collection for the evaluation of H3K27 methylations has been modified to a whole blood sample collection. • The required use of highly effective birth control for women of child bearing potential has been modified from 28D to during study follow-up to be consistent with the updated IB.

10 Aug 2021

The main purpose of this amendment was to add an exploratory PD marker. To facilitate this measurement, additional whole blood samples were collected in MAK683-treated participants.

16 Mar 2023

The main purpose of this amendment was to modify the study conduct following the enrollment halt that came into effect on 08-Nov-2022, by reducing the assessment burden and minimizing data collection in ongoing trial subjects. The definition of end of study was revised to include the option for participants still on study treatment and who, in the opinion of the investigator, are 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 participants. Furthermore, use of live vaccines was added as one of the prohibited concomitant therapies.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A phase I/II, multicenter, open-label study of MAK683 in adult patients with advanced malignancies

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Incidence of dose limiting toxicities (DLTs)

Primary: Incidence of dose limiting toxicities (DLTs)

Primary: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Primary: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Primary: Incidence of dose interruptions and dose reductions

Primary: Incidence of dose interruptions and dose reductions

Primary: Dose intensity

Primary: Dose intensity

Primary: Relative Dose intensity

Primary: Relative Dose intensity

Secondary: Overall Response Rate (ORR) - DLBCL

Secondary: Overall Response Rate (ORR) - DLBCL

Secondary: Overall Response Rate (ORR) - SOLID TUMORS

Secondary: Overall Response Rate (ORR) - SOLID TUMORS

Secondary: Best Overall Response (BOR) - DLBCL

Secondary: Best Overall Response (BOR) - DLBCL

Secondary: Best Overall Response (BOR) - SOLID TUMORS

Secondary: Best Overall Response (BOR) - SOLID TUMORS

Secondary: Duration of overall response (DOR) - DLBCL

Secondary: Duration of overall response (DOR) - DLBCL

Secondary: Duration of overall response (DOR) - SOLID TUMORS

Secondary: Duration of overall response (DOR) - SOLID TUMORS

Secondary: Progression-free survival (PFS) - DLBCL

Secondary: Progression-free survival (PFS) - DLBCL

Secondary: Progression-free survival (PFS) - SOLID TUMORS

Secondary: Progression-free survival (PFS) - SOLID TUMORS

Secondary: Peak Plasma Concentration (Cmax) of MAK683

Secondary: Peak Plasma Concentration (Cmax) of MAK683

Secondary: Area Under the Plasma Concentration (AUClast) Time Curve of MAK683

Secondary: Area Under the Plasma Concentration (AUClast) Time Curve of MAK683

Secondary: Area Under the Plasma Concentration (AUCinf) Time Curve of MAK683

Secondary: Area Under the Plasma Concentration (AUCinf) Time Curve of MAK683

Secondary: Time to Peak Plasma Concentration (Tmax) of MAK683

Secondary: Time to Peak Plasma Concentration (Tmax) of MAK683

Secondary: Change from baseline H3K27 tri methylation level in PBMC

Secondary: Change from baseline H3K27 tri methylation level in PBMC

Post-hoc: All collected deaths

Post-hoc: All collected deaths

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A phase I/II, multicenter, open-label study of MAK683 in adult patients with advanced malignancies