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Clinical Trial Results:
A PHASE 1A/1B, MULTICENTER, OPEN LABEL, DOSE-FINDING STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PRELIMINARY EFFICACY OF THE DUAL DNA-PK AND TOR KINASE INHIBITOR, CC-115, ADMINISTERED ORALLY TO SUBJECTS WITH ADVANCED SOLID TUMORS AND HEMATOLOGIC MALIGNANCIES

Summary
EudraCT number	2011-004558-24
Trial protocol	ES FR
Global end of trial date	12 Mar 2021

Results information
Results version number	v1(current)
This version publication date	20 Mar 2022
First version publication date	20 Mar 2022
Other versions

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

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Trial information

Top of page

Sponsor protocol code

CC-115-ST-001

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chaussée de la Hulpe 185, Brussels, Belgium, 1170

Public contact

EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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

25 Jun 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

12 Mar 2021

Was the trial ended prematurely?

Main objective of the trial

To determine the safety and tolerability of CC-115 when administered orally and to determine the pharmacokinetics (PK) of CC-115.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

25 Apr 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 6

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Spain: 15

Country: Number of subjects enrolled

United States: 94

Worldwide total number of subjects

118

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

Screening details

118 participants were treated. 44 participants were treated in Part A, 74 participants were treated in Part B

Period 1 title

Dose Escalation + Dose Expansion (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

QD 0.5 mg

Arm description

CC-115 administered once a day at a dose of 0.5 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

0.5 mg QD (once a day)

QD 1 mg

Arm description

CC-115 administered once a day at a dose of 1 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1 mg QD (once a day)

QD 2 mg

Arm description

CC-115 administered once a day at a dose of 2 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2 mg QD (once a day)

QD 4 mg

Arm description

CC-115 administered once a day at a dose of 4 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

4 mg QD (once a day)

QD 8 mg

Arm description

CC-115 administered once a day at a dose of 8 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

8 mg QD (once a day)

QD 16 mg

Arm description

CC-115 administered once a day at a dose of 16 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

16 mg QD (once a day)

QD 25 mg

Arm description

CC-115 administered once a day at a dose of 25 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

25 mg QD (once a day)

QD 40 mg

Arm description

CC-115 administered once a day at a dose of 40 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

40 mg QD (once a day)

BID 10 mg

Arm description

CC-115 administered twice a day at a dose of 10 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 mg BID (twice a day)

BID 15 mg

Arm description

CC-115 administered twice a day at a dose of 15 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

15 mg BID (twice a day)

Dose Expansion cohort - HNSCC

Arm description

Participants diagnosed with Head and Neck Squamous Cell Carcinoma (HNSCC). CC-115 administered twice a day at a dose of 10 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 mg BID (twice a day)

Dose Expansion cohort - GBM

Arm description

Participants diagnosed with Glioblastoma Multiforme (GBM). CC-115 administered twice a day at a dose of 10 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 mg BID (twice a day)

Dose Expansion cohort - CLL/SLL

Arm description

Participants diagnosed with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). CC-115 administered twice a day at a dose of 10 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 mg BID (twice a day)

Dose Expansion cohort - CRPC

Arm description

Participants diagnosed with Castration-Resistant Prostate Cancer (CRPC). CC-115 administered twice a day at a dose of 10 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 mg BID (twice a day)

Dose Expansion cohort - ES

Arm description

Participants diagnosed with Ewing's sarcoma (ES). CC-115 administered twice a day at a dose of 10 mg

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 mg BID (twice a day)

Dose Expansion cohort - BA/Food Effect

Arm description

Participants diagnosed with any tumor type and who were treated in the bioavailability(BA)/food effect substudy. CC-115 administered under fasted or fed conditions at 10 mg dose

Arm type

Experimental

Investigational medicinal product name

CC-115

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 mg under fasted or fed conditions

Number of subjects in period 1	QD 0.5 mg	QD 1 mg	QD 2 mg	QD 4 mg	QD 8 mg	QD 16 mg	QD 25 mg	QD 40 mg	BID 10 mg	BID 15 mg	Dose Expansion cohort - HNSCC	Dose Expansion cohort - GBM	Dose Expansion cohort - CLL/SLL	Dose Expansion cohort - CRPC	Dose Expansion cohort - ES	Dose Expansion cohort - BA/Food Effect
Started	1	1	1	4	6	6	7	6	6	6	18	14	8	12	10	12
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	1	1	1	4	6	6	7	6	6	6	18	14	8	12	10	12
Adverse event, serious fatal	-	-	-	-	-	-	1	-	-	-	1	-	-	-	-	1
Physician decision	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-	-
Consent withdrawn by subject	-	-	-	-	-	-	1	1	1	2	3	2	-	1	1	2
Disease progression	1	1	1	3	6	5	4	2	4	3	10	8	4	5	9	6
Adverse event, non-fatal	-	-	-	1	-	-	1	-	-	1	-	3	2	5	-	-
Other reasons	-	-	-	-	-	-	-	3	1	-	4	1	2	1	-	3

Baseline characteristics

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Reporting group title

QD 0.5 mg

Reporting group description

CC-115 administered once a day at a dose of 0.5 mg

Reporting group title

QD 1 mg

Reporting group description

CC-115 administered once a day at a dose of 1 mg

Reporting group title

QD 2 mg

Reporting group description

CC-115 administered once a day at a dose of 2 mg

Reporting group title

QD 4 mg

Reporting group description

CC-115 administered once a day at a dose of 4 mg

Reporting group title

QD 8 mg

Reporting group description

CC-115 administered once a day at a dose of 8 mg

Reporting group title

QD 16 mg

Reporting group description

CC-115 administered once a day at a dose of 16 mg

Reporting group title

QD 25 mg

Reporting group description

CC-115 administered once a day at a dose of 25 mg

Reporting group title

QD 40 mg

Reporting group description

CC-115 administered once a day at a dose of 40 mg

Reporting group title

BID 10 mg

Reporting group description

CC-115 administered twice a day at a dose of 10 mg

Reporting group title

BID 15 mg

Reporting group description

CC-115 administered twice a day at a dose of 15 mg

Reporting group title

Dose Expansion cohort - HNSCC

Reporting group description

Participants diagnosed with Head and Neck Squamous Cell Carcinoma (HNSCC). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - GBM

Reporting group description

Participants diagnosed with Glioblastoma Multiforme (GBM). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - CLL/SLL

Reporting group description

Participants diagnosed with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - CRPC

Reporting group description

Participants diagnosed with Castration-Resistant Prostate Cancer (CRPC). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - ES

Reporting group description

Participants diagnosed with Ewing's sarcoma (ES). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - BA/Food Effect

Reporting group description

Participants diagnosed with any tumor type and who were treated in the bioavailability(BA)/food effect substudy. CC-115 administered under fasted or fed conditions at 10 mg dose

Reporting group values	QD 0.5 mg	QD 1 mg	QD 2 mg	QD 4 mg	QD 8 mg	QD 16 mg	QD 25 mg	QD 40 mg	BID 10 mg	BID 15 mg	Dose Expansion cohort - HNSCC	Dose Expansion cohort - GBM	Dose Expansion cohort - CLL/SLL	Dose Expansion cohort - CRPC	Dose Expansion cohort - ES	Dose Expansion cohort - BA/Food Effect	Total
Number of subjects	1	1	1	4	6	6	7	6	6	6	18	14	8	12	10	12	118
Age Categorical
Units: Subjects
Adults (18-64 years)	0	1	1	3	6	5	7	4	4	3	15	13	7	3	10	6	88
From 65-84 years	1	0	0	1	0	1	0	2	2	3	3	1	1	9	0	6	30
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	73.0 ± 99999	58.0 ± 99999	57.0 ± 99999	49.8 ± 15.76	49.5 ± 18.92	47.0 ± 18.69	47.3 ± 15.27	60.3 ± 8.73	59.3 ± 10.60	62.2 ± 8.91	56.0 ± 10.47	53.0 ± 10.04	58.4 ± 7.69	67.8 ± 5.89	36.6 ± 12.86	60.8 ± 11.53	-
Gender Categorical
Units: Subjects
Female	1	0	0	3	2	4	4	3	3	5	5	4	3	0	2	8	47
Male	0	1	1	1	4	2	3	3	3	1	13	10	5	12	8	4	71
Race
Units: Subjects
Asian	0	0	1	1	1	3	1	0	0	0	0	0	0	0	0	0	7
Black or African American	0	0	0	0	0	1	0	1	0	0	0	1	0	0	0	1	4
White	1	1	0	3	5	2	5	5	6	6	18	12	8	12	10	10	104
Other	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	1	3
Ethnicity
Units: Subjects
Hispanic or Latino	0	0	0	1	0	0	0	0	0	0	3	3	0	0	0	0	7
Not Hispanic or Latino	1	1	1	3	6	6	7	6	6	6	15	11	8	12	10	12	111

End points

Top of page

Reporting group title

QD 0.5 mg

Reporting group description

CC-115 administered once a day at a dose of 0.5 mg

Reporting group title

QD 1 mg

Reporting group description

CC-115 administered once a day at a dose of 1 mg

Reporting group title

QD 2 mg

Reporting group description

CC-115 administered once a day at a dose of 2 mg

Reporting group title

QD 4 mg

Reporting group description

CC-115 administered once a day at a dose of 4 mg

Reporting group title

QD 8 mg

Reporting group description

CC-115 administered once a day at a dose of 8 mg

Reporting group title

QD 16 mg

Reporting group description

CC-115 administered once a day at a dose of 16 mg

Reporting group title

QD 25 mg

Reporting group description

CC-115 administered once a day at a dose of 25 mg

Reporting group title

QD 40 mg

Reporting group description

CC-115 administered once a day at a dose of 40 mg

Reporting group title

BID 10 mg

Reporting group description

CC-115 administered twice a day at a dose of 10 mg

Reporting group title

BID 15 mg

Reporting group description

CC-115 administered twice a day at a dose of 15 mg

Reporting group title

Dose Expansion cohort - HNSCC

Reporting group description

Participants diagnosed with Head and Neck Squamous Cell Carcinoma (HNSCC). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - GBM

Reporting group description

Participants diagnosed with Glioblastoma Multiforme (GBM). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - CLL/SLL

Reporting group description

Participants diagnosed with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - CRPC

Reporting group description

Participants diagnosed with Castration-Resistant Prostate Cancer (CRPC). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - ES

Reporting group description

Participants diagnosed with Ewing's sarcoma (ES). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - BA/Food Effect

Reporting group description

Participants diagnosed with any tumor type and who were treated in the bioavailability(BA)/food effect substudy. CC-115 administered under fasted or fed conditions at 10 mg dose

Subject analysis set title

Bioavailability/Food Effect Cohort - fasting - capsule

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in the Dose expansion cohort - BA/Food Effect under fasted conditions - capsule formulation

Subject analysis set title

Bioavailability/Food Effect Cohort - fasting - tablet

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in the Dose expansion cohort - BA/Food Effect under fasted conditions - tablet formulation

Subject analysis set title

Bioavailability/Food Effect Cohort - fed

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in the Dose expansion cohort - BA/Food Effect under fed conditions - tablet formulation

Primary: Number of Participants Experiencing Dose-Limiting Toxicity (DLT)

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End point title

Number of Participants Experiencing Dose-Limiting Toxicity (DLT) ^[1] ^[2]

End point description

Dose-Limiting Toxicity is defined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4. Briefly, a DLT is any: - clinically relevant AE ≥ grade 3 that is suspected to be related to CC-115 and that commences within 28 days of first dose (with some exceptions). - Clinically relevant laboratory abnormality that is suspected to be related to CC-115 and that commences within 28 days of first dose (Cycle 1) and is ≥ grade 3, or any grade 4 laboratory abnormality that is suspected to be related to CC-115 regardless of clinical relevance. - Hyperglycemia meeting specific criteria. - Hematological toxicities meeting specific criteria. - Any AE suspected to be CC-115 related and necessitating dose reduction during Cycle 1.

End point type

Primary

End point timeframe

From first dose up to 28 days after first dose

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 analyses were performed for this endpoint
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was not evaluated in all the cohorts

End point values	QD 0.5 mg	QD 1 mg	QD 2 mg	QD 4 mg	QD 8 mg	QD 16 mg	QD 25 mg	QD 40 mg	BID 10 mg	BID 15 mg
Number of subjects analysed	1	1	1	3	6	6	6	5	6	6
Units: Participants	0	0	0	0	0	1	1	2	0	2

No statistical analyses for this end point

Primary: Maximum Observed Concentration (Cmax)

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End point title

Maximum Observed Concentration (Cmax) ^[3] ^[4]

End point description

End point type

Primary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 15

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 analyses were performed for this endpoint
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was not evaluated in all the cohorts

QD 0.5 mg

QD 1 mg

QD 2 mg

QD 4 mg

QD 8 mg

QD 16 mg

QD 25 mg

QD 40 mg

BID 10 mg

BID 15 mg

Dose Expansion cohort - HNSCC

Dose Expansion cohort - CRPC

Number of subjects analysed

Units: ng/mL

geometric mean (geometric coefficient of variation)

Cycle 1 Day 1

8.70 ± 99999

9.32 ± 99999

10.41 ± 99999

28.49 ± 19.3

36.07 ± 29.4

88.68 ± 72.6

173.45 ± 27.9

167.42 ± 53.3

51.80 ± 22.8

133.98 ± 43.5

42.39 ± 69.75

66.17 ± 33.10

Cycle 1 Day 15

8.65 ± 99999

8.11 ± 99999

13.16 ± 99999

30.51 ± 81.4

40.93 ± 25.6

118.22 ± 87.0

197.87 ± 40.4

243.64 ± 49.1

75.24 ± 45.2

161.99 ± 42.8

68.66 ± 43.17

112.41 ± 45.70

No statistical analyses for this end point

Primary: Maximum Observed Concentration (Cmax) - BA/Food Effect Cohort

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End point title

Maximum Observed Concentration (Cmax) - BA/Food Effect Cohort ^[5]

End point description

End point type

Primary

End point timeframe

Period 1 Day 1, Period 2 Day 1, Period 3 Day 1

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 analyses were performed for this endpoint

End point values	Bioavailability/Food Effect Cohort - fasting - capsule	Bioavailability/Food Effect Cohort - fasting - tablet	Bioavailability/Food Effect Cohort - fed
Number of subjects analysed	4	4	4
Units: ug/L
geometric mean (geometric coefficient of variation)
Period 1 Day 1	91.12 ± 61.59	50.12 ± 75.90	55.82 ± 39.55
Period 2 Day 1	84.48 ± 68.17	75.33 ± 69.94	35.90 ± 49.39
Period 3 Day 1	73.73 ± 92.36	122.49 ± 26.22	49.15 ± 31.25

No statistical analyses for this end point

Primary: Area Under the Concentration-Time Curve (AUC)

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End point title

Area Under the Concentration-Time Curve (AUC) ^[6] ^[7]

End point description

Multiple AUC (0 to X hours) were determined and are presented here. Results reported represent data collection at Cycle 1 Day 15 for AUC8, AUC12, AUC24 and AUCt. Results reported represent data collection at Cycle 1 Day 1 for AUC-inf.

End point type

Primary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 15

Notes
[6] - 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 analyses were performed for this endpoint
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was not evaluated in all the cohorts

QD 0.5 mg

QD 1 mg

QD 2 mg

QD 4 mg

QD 8 mg

QD 16 mg

QD 25 mg

QD 40 mg

BID 10 mg

BID 15 mg

Dose Expansion cohort - HNSCC

Dose Expansion cohort - CRPC

Number of subjects analysed

Units: ng*h/mL

geometric mean (geometric coefficient of variation)

AUC8

42.18 ± 99999

47.39 ± 99999

60.03 ± 99999

169.13 ± 70.2

181.82 ± 47.6

588.01 ± 115.0

943.05 ± 52.8

1285.54 ± 42.6

304.37 ± 35.8

802.75 ± 53.7

337.52 ± 62.17

547.19 ± 62.77

AUC12

53.21 ± 99999

65.79 ± 99999

72.95 ± 99999

234.18 ± 62.8

220.74 ± 57.1

757.98 ± 129.7

1180.32 ± 57.8

1732.76 ± 40.3

383.04 ± 43.4

1027.96 ± 55.7

374.29 ± 32.71

780.04 ± 65.58

AUC24

72.31 ± 99999

108.37 ± 99999

94.28 ± 99999

350.11 ± 62.9

285.56 ± 73.6

1094.97 ± 149.0

1573.20 ± 67.0

2650.16 ± 36.9

766.07 ± 43.4

2055.93 ± 55.7

99999 ± 99999

AUC-inf

76.15 ± 99999

93.07 ± 99999

57.45 ± 99999

236.90 ± 48.4

237.47 ± 64.1

624.86 ± 81.7

1912.20 ± 92.1

2129.67 ± 45.3

605.32 ± 60.7

1306.58 ± 48.4

99999 ± 99999

AUCt

72.31 ± 99999

108.37 ± 99999

94.28 ± 99999

350.11 ± 62.9

285.56 ± 73.6

1094.97 ± 149.0

1573.20 ± 67.0

2650.16 ± 36.9

506.67 ± 53.2

1657.68 ± 64.8

374.29 ± 32.71

780.04 ± 65.58

No statistical analyses for this end point

Primary: Area Under the Concentration-Time Curve (AUCinf) - BA/Food Effect Cohort

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End point title

Area Under the Concentration-Time Curve (AUCinf) - BA/Food Effect Cohort ^[8]

End point description

End point type

Primary

End point timeframe

Period 1 Day 1, Period 2 Day 1, Period 3 Day 1

Notes
[8] - 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 analyses were performed for this endpoint

End point values	Bioavailability/Food Effect Cohort - fasting - capsule	Bioavailability/Food Effect Cohort - fasting - tablet	Bioavailability/Food Effect Cohort - fed
Number of subjects analysed	4	4	4
Units: h*ug/L
geometric mean (geometric coefficient of variation)
Period 1 Day 1	870.20 ± 79.06	505.24 ± 155.44	585.96 ± 96.77
Period 2 Day 1	621.70 ± 115.72	832.46 ± 75.74	720.13 ± 3.87
Period 3 Day 1	1023.01 ± 65.26	725.24 ± 79.47	666.99 ± 99999

No statistical analyses for this end point

Primary: Time to Maximum Concentration (Tmax)

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End point title

Time to Maximum Concentration (Tmax) ^[9] ^[10]

End point description

End point type

Primary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 15

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

QD 0.5 mg

QD 1 mg

QD 2 mg

QD 4 mg

QD 8 mg

QD 16 mg

QD 25 mg

QD 40 mg

BID 10 mg

BID 15 mg

Dose Expansion cohort - HNSCC

Dose Expansion cohort - CRPC

Number of subjects analysed

Units: hr

arithmetic mean (standard deviation)

Cycle 1 Day 1

0.52 ± 99999

3.00 ± 99999

1.50 ± 99999

1.76 ± 0.876

1.92 ± 1.530

2.44 ± 0.940

2.67 ± 1.258

2.50 ± 1.478

2.11 ± 0.998

4.88 ± 9.215

1.714 ± 0.9512

1.571 ± 0.6726

Cycle 1 Day 15

1.50 ± 99999

1.67 ± 99999

2.13 ± 99999

3.36 ± 3.165

1.92 ± 1.004

2.04 ± 0.826

1.61 ± 0.829

3.02 ± 0.044

1.55 ± 0.677

1.83 ± 0.684

2.250 ± 1.3363

2.000 ± 1.5000

No statistical analyses for this end point

Primary: Time to Maximum Concentration (Tmax) - BA/Food Effect Cohort

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End point title

Time to Maximum Concentration (Tmax) - BA/Food Effect Cohort ^[11]

End point description

End point type

Primary

End point timeframe

Period 1 Day 1, Period 2 Day 1, Period 3 Day 1

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed for this endpoint

End point values	Bioavailability/Food Effect Cohort - fasting - capsule	Bioavailability/Food Effect Cohort - fasting - tablet	Bioavailability/Food Effect Cohort - fed
Number of subjects analysed	4	4	4
Units: hr
arithmetic mean (standard deviation)
Period 1 Day 1	1.875 ± 0.2500	2.375 ± 0.7500	3.000 ± 1.4142
Period 2 Day 1	1.875 ± 0.8539	1.500 ± 0.4082	9.000 ± 10.0995
Period 3 Day 1	2.250 ± 0.8660	0.875 ± 0.4787	6.500 ± 3.0000

No statistical analyses for this end point

Primary: Terminal Half-Life (t1/2)

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End point title

Terminal Half-Life (t1/2) ^[12] ^[13]

End point description

End point type

Primary

End point timeframe

Cycle 1 Day 1

Notes
[12] - 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 analyses were performed for this endpoint
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was not evaluated in all the cohorts

QD 0.5 mg

QD 1 mg

QD 2 mg

QD 4 mg

QD 8 mg

QD 16 mg

QD 25 mg

QD 40 mg

BID 10 mg

BID 15 mg

Dose Expansion cohort - HNSCC

Dose Expansion cohort - CRPC

Number of subjects analysed

Units: hr

arithmetic mean (standard deviation)

11.93 ± 99999

10.60 ± 99999

6.17 ± 99999

6.61 ± 1.145

6.33 ± 2.098

7.63 ± 2.718

8.55 ± 4.264

7.96 ± 3.509

4.04 ± 0.827

5.68 ± 2.748

3.478 ± 2.0857

4.426 ± 1.6685

No statistical analyses for this end point

Primary: Terminal Half-Life (t1/2) - BA/Food Effect Cohort

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End point title

Terminal Half-Life (t1/2) - BA/Food Effect Cohort ^[14]

End point description

End point type

Primary

End point timeframe

Period 1 Day 1, Period 2 Day 1, Period 3 Day 1

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed for this endpoint

End point values	Bioavailability/Food Effect Cohort - fasting - capsule	Bioavailability/Food Effect Cohort - fasting - tablet	Bioavailability/Food Effect Cohort - fed
Number of subjects analysed	4	4	4
Units: hr
arithmetic mean (standard deviation)
Period 1 Day 1	14.350 ± 8.2051	9.686 ± 5.2947	8.793 ± 4.2063
Period 2 Day 1	8.569 ± 4.0371	13.261 ± 5.2962	11.286 ± 4.9139
Period 3 Day 1	13.301 ± 3.4328	7.856 ± 3.8410	11.896 ± 99999

No statistical analyses for this end point

Primary: Apparent Total Body Clearance (CL/F)

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End point title

Apparent Total Body Clearance (CL/F) ^[15] ^[16]

End point description

End point type

Primary

End point timeframe

Cycle 1 Day 1

Notes
[15] - 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 analyses were performed for this endpoint
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was not evaluated in all the cohorts

QD 0.5 mg

QD 1 mg

QD 2 mg

QD 4 mg

QD 8 mg

QD 16 mg

QD 25 mg

QD 40 mg

BID 10 mg

BID 15 mg

Dose Expansion cohort - HNSCC

Dose Expansion cohort - CRPC

Number of subjects analysed

Units: mL/hr

geometric mean (geometric coefficient of variation)

6565.92 ± 99999

10744.76 ± 99999

34811.99 ± 99999

16884.66 ± 48.4

33687.82 ± 64.1

25605.72 ± 81.7

13073.92 ± 92.1

18782.26 ± 45.3

33040.44 ± 60.7

22960.71 ± 48.4

45310 ± 154.48

22940 ± 53.42

No statistical analyses for this end point

Primary: Apparent Total Body Clearance (CL/F) - BA/Food Effect Cohort

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End point title

Apparent Total Body Clearance (CL/F) - BA/Food Effect Cohort ^[17]

End point description

End point type

Primary

End point timeframe

Period 1 Day 1, Period 2 Day 1, Period 3 Day 1

Notes
[17] - 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 analyses were performed for this endpoint

End point values	Bioavailability/Food Effect Cohort - fasting - capsule	Bioavailability/Food Effect Cohort - fasting - tablet	Bioavailability/Food Effect Cohort - fed
Number of subjects analysed	4	4	4
Units: L/hr
geometric mean (geometric coefficient of variation)
Period 1 Day 1	11.49 ± 79.06	19.79 ± 155.44	17.07 ± 96.77
Period 2 Day 1	16.08 ± 115.72	12.01 ± 75.74	13.89 ± 3.87
Period 3 Day 1	9.78 ± 65.26	13.79 ± 79.47	14.99 ± 99999

No statistical analyses for this end point

Primary: Apparent Volume of Distribution (Vz/F)

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End point title

Apparent Volume of Distribution (Vz/F) ^[18] ^[19]

End point description

End point type

Primary

End point timeframe

Cycle 1 Day 1

Notes
[18] - 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 analyses were performed for this endpoint
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was not evaluated in all the cohorts

QD 0.5 mg

QD 1 mg

QD 2 mg

QD 4 mg

QD 8 mg

QD 16 mg

QD 25 mg

QD 40 mg

BID 10 mg

BID 15 mg

Dose Expansion cohort - HNSCC

Dose Expansion cohort - CRPC

Number of subjects analysed

Units: mL

geometric mean (geometric coefficient of variation)

113002.05 ± 99999

164320.03 ± 99999

310044.82 ± 99999

159056.04 ± 33.0

293636.64 ± 57.1

263877.04 ± 103.5

149036.99 ± 42.4

200931.87 ± 28.9

189478.26 ± 35.9

172900.26 ± 36.3

200450 ± 63.45

136170 ± 25.44

No statistical analyses for this end point

Primary: Apparent Volume of Distribution (Vz/F) - BA/Food Effect Cohort

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End point title

Apparent Volume of Distribution (Vz/F) - BA/Food Effect Cohort ^[20]

End point description

End point type

Primary

End point timeframe

Period 1 Day1, Period 2 Day 1, Period 3 Day 1

Notes
[20] - 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 analyses were performed for this endpoint

End point values	Bioavailability/Food Effect Cohort - fasting - capsule	Bioavailability/Food Effect Cohort - fasting - tablet	Bioavailability/Food Effect Cohort - fed
Number of subjects analysed	4	4	4
Units: Liters
geometric mean (geometric coefficient of variation)
Period 1 Day 1	213.60 ± 179.03	229.85 ± 42.80	201.49 ± 58.84
Period 2 Day 1	185.77 ± 61.82	217.90 ± 121.48	215.12 ± 42.93
Period 3 Day 1	183.06 ± 56.26	145.21 ± 37.93	257.31 ± 99999

No statistical analyses for this end point

Primary: Drug Accumulation Ratio (Rac)

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End point title

Drug Accumulation Ratio (Rac) ^[21] ^[22]

End point description

End point type

Primary

End point timeframe

Cycle 1 Day 15

Notes
[21] - 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 analyses were performed for this endpoint
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was not evaluated in all the cohorts

QD 0.5 mg

QD 1 mg

QD 2 mg

QD 4 mg

QD 8 mg

QD 16 mg

QD 25 mg

QD 40 mg

BID 10 mg

BID 15 mg

Dose Expansion cohort - HNSCC

Dose Expansion cohort - CRPC

Number of subjects analysed

Units: Ratio

arithmetic mean (standard deviation)

1.18 ± 99999

1.63 ± 99999

1.12 ± 99999

1.33 ± 0.250

1.15 ± 0.183

1.36 ± 0.280

1.15 ± 0.075

2.94 ± 3.485

2.35 ± 0.599

4.33 ± 2.716

3.115 ± 2.8558

1.667 ± 0.3008

No statistical analyses for this end point

Secondary: Change from Baseline in Blood Levels of Phosphorylated 4E-Binding Protein 1 (pE4-BP1)

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End point title

Change from Baseline in Blood Levels of Phosphorylated 4E-Binding Protein 1 (pE4-BP1) ^[23]

End point description

Changes in pE4-BP1 (CD91+) are presented here

End point type

Secondary

End point timeframe

From baseline to Cycle 1 Day 2 (pre-dose)

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

End point values	QD 0.5 mg	QD 1 mg	QD 2 mg	QD 4 mg	QD 8 mg	QD 16 mg	QD 25 mg	QD 40 mg	BID 10 mg	BID 15 mg
Number of subjects analysed	0 ^[24]	1	1	4	4	6	5	4	0 ^[25]	0 ^[26]
Units: Percent change from baseline
arithmetic mean (standard deviation)	±	21.6 ± 99999	-8.9 ± 99999	10.7 ± 26.31	-3.4 ± 15.87	-33.8 ± 21.03	-14.4 ± 20.43	6.9 ± 34.94	±	±

Notes
[24] - No subjects analyzed in this cohort
[25] - No subjects analyzed in this cohort
[26] - No subjects analyzed in this cohort

No statistical analyses for this end point

Secondary: Change from Baseline in the Percent Ratio of Phosphorylated AKT (p-AKT)/ Total AKT

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End point title

Change from Baseline in the Percent Ratio of Phosphorylated AKT (p-AKT)/ Total AKT ^[27]

End point description

End point type

Secondary

End point timeframe

From baseline to Cycle 1 Day 2 (pre-dose)

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

End point values	QD 0.5 mg	QD 1 mg	QD 2 mg	QD 4 mg	QD 8 mg	QD 16 mg	QD 25 mg	QD 40 mg	BID 10 mg	BID 15 mg
Number of subjects analysed	0 ^[28]	0 ^[29]	1	4	4	6	6	6	0 ^[30]	0 ^[31]
Units: Percent change from baseline
arithmetic mean (standard deviation)	±	±	-40.8 ± 99999	23.7 ± 96.75	-47.6 ± 14.18	7.2 ± 70.69	-25.8 ± 40.05	-57.1 ± 27.51	±	±

Notes
[28] - No subjects analyzed in this cohort
[29] - No subjects analyzed in this cohort
[30] - No subjects analyzed in this cohort
[31] - No subjects analyzed in this cohort

No statistical analyses for this end point

Secondary: Change from Baseline in the Levels of UV-Stimulated phosphorylated DNA-dependent Protein Kinase (pDNA-PK)

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End point title

Change from Baseline in the Levels of UV-Stimulated phosphorylated DNA-dependent Protein Kinase (pDNA-PK) ^[32]

End point description

From baseline to Cycle 1 Day 15

End point type

Secondary

End point timeframe

pDNA-PK measured as H-score

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was not evaluated in all the cohorts

End point values	QD 0.5 mg	QD 1 mg	QD 2 mg	QD 4 mg	QD 8 mg	QD 16 mg	QD 25 mg	QD 40 mg	BID 10 mg	BID 15 mg
Number of subjects analysed	1	1	1	3	6	5	6	4	0 ^[33]	0 ^[34]
Units: Percent change from baseline
arithmetic mean (standard deviation)	-16.7 ± 99999	14.9 ± 99999	1.5 ± 99999	2.2 ± 19.30	-3.1 ± 12.58	2.7 ± 21.20	1.9 ± 24.68	17.9 ± 24.88	±	±

Notes
[33] - No subjects analyzed in this cohort
[34] - No subjects analyzed in this cohort

No statistical analyses for this end point

Secondary: Objective Response Rate (ORR)

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End point title

Objective Response Rate (ORR)

End point description

ORR is defined as the percentage of participants achieving a Complete Response (CR) or Partial Response (PR). Results are presented separately for Confirmed and Unconfirmed Responses. Unconfirmed Responses are based on investigator assessment using tumor-appropriate evaluation criteria.

End point type

Secondary

End point timeframe

From first dose to end of study, assessed every 2 cycles for the first 6 cycles, then every 3 cycles through the end of first year on study and then every 6 cycles thereafter

QD 0.5 mg

QD 1 mg

QD 2 mg

QD 4 mg

QD 8 mg

QD 16 mg

QD 25 mg

QD 40 mg

BID 10 mg

BID 15 mg

Dose Expansion cohort - HNSCC

Dose Expansion cohort - GBM

Dose Expansion cohort - CLL/SLL

Dose Expansion cohort - CRPC

Dose Expansion cohort - ES

Dose Expansion cohort - BA/Food Effect

Number of subjects analysed

0 ^[35]

Units: Percent of Participants

number (confidence interval 95%)

Unconfirmed responses

0 (-99999 to 99999)

16.7 (0.4 to 64.1)

0 (-99999 to 99999)

16.7 (0.4 to 64.1)

0 (-99999 to 99999)

0 (0 to 19.5)

( to )

12.5 (0.3 to 52.7)

0 (0 to 28.5)

0 (0 to 33.6)

18.2 (2.3 to 51.8)

Confirmed responses

0 (-99999 to 99999)

16.7 (0.4 to 64.1)

0 (-99999 to 99999)

0 (0 to 19.5)

( to )

99999 (99999 to 99999)

0 (0 to 33.6)

0 (0 to 28.5)

Notes
[35] - No measurements available for this cohort

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From first dose to 100 days following last dose

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

QD 0.5 mg

Reporting group description

CC-115 administered once a day at a dose of 0.5 mg

Reporting group title

QD 1 mg

Reporting group description

CC-115 administered once a day at a dose of 1 mg

Reporting group title

QD 2 mg

Reporting group description

CC-115 administered once a day at a dose of 2 mg

Reporting group title

QD 4 mg

Reporting group description

CC-115 administered once a day at a dose of 4 mg

Reporting group title

QD 8 mg

Reporting group description

CC-115 administered once a day at a dose of 8 mg

Reporting group title

QD 16 mg

Reporting group description

CC-115 administered once a day at a dose of 16 mg

Reporting group title

QD 25 mg

Reporting group description

CC-115 administered once a day at a dose of 25 mg

Reporting group title

QD 40 mg

Reporting group description

CC-115 administered once a day at a dose of 40 mg

Reporting group title

Dose Expansion cohort - HNSCC

Reporting group description

Participants diagnosed with Head and Neck Squamous Cell Carcinoma (HNSCC). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

BID 15 mg

Reporting group description

CC-115 administered twice a day at a dose of 15 mg

Reporting group title

BID 10 mg

Reporting group description

CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - GBM

Reporting group description

Participants diagnosed with Glioblastoma Multiforme (GBM). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - ES

Reporting group description

Participants diagnosed with Ewing's sarcoma (ES). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - CRPC

Reporting group description

Participants diagnosed with Castration-Resistant Prostate Cancer (CRPC). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - CLL/SLL

Reporting group description

Participants diagnosed with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). CC-115 administered twice a day at a dose of 10 mg

Reporting group title

Dose Expansion cohort - BA/Food Effect

Reporting group description

Participants diagnosed with any tumor type and who were treated in the bioavailability(BA)/food effect substudy. CC-115 administered under fasted or fed conditions at 10 mg dose

QD 0.5 mg

QD 1 mg

QD 2 mg

QD 4 mg

QD 8 mg

QD 16 mg

QD 25 mg

QD 40 mg

Dose Expansion cohort - HNSCC

BID 15 mg

BID 10 mg

Dose Expansion cohort - GBM

Dose Expansion cohort - ES

Dose Expansion cohort - CRPC

Dose Expansion cohort - CLL/SLL

Dose Expansion cohort - BA/Food Effect

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 1 (0.00%)

1 / 1 (100.00%)

0 / 1 (0.00%)

3 / 4 (75.00%)

2 / 6 (33.33%)

3 / 6 (50.00%)

2 / 7 (28.57%)

2 / 6 (33.33%)

8 / 18 (44.44%)

2 / 6 (33.33%)

3 / 6 (50.00%)

5 / 14 (35.71%)

4 / 10 (40.00%)

4 / 12 (33.33%)

5 / 8 (62.50%)

7 / 12 (58.33%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Adenocarcinoma gastric

subjects affected / exposed

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (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

Alveolar soft part sarcoma metastatic

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (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

Cancer pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cholangiocarcinoma

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (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

Ewing's sarcoma metastatic

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Leiomyosarcoma

subjects affected / exposed

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (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

Richter's syndrome

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Synovial sarcoma

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

Tumour pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Deep vein thrombosis

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 14 (7.14%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (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

Hypotension

subjects affected / exposed

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Asthenia

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 14 (7.14%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fatigue

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 14 (7.14%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

General physical health deterioration

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

2 / 12 (16.67%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

Non-cardiac chest pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain

subjects affected / exposed

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (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

Chronic obstructive pulmonary disease

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

0 / 1 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

2 / 6 (33.33%)

0 / 6 (0.00%)

0 / 14 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoxia

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (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 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (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 venous thrombosis

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (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 / 1 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

2 / 10 (20.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

Psychiatric disorders

Homicidal ideation

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Aspartate aminotransferase increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood alkaline phosphatase increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Femoral neck fracture

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Muscle strain

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subdural haemorrhage

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 14 (7.14%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wound dehiscence

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Aortic valve disease

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Headache

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

1 / 14 (7.14%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 14 (7.14%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Thrombocytopenia

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal wall haematoma

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastric perforation

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (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 / 1 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (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

Pancreatitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Acute hepatic failure

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 12 (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

Bile duct obstruction

subjects affected / exposed

0 / 1 (0.00%)

1 / 1 (100.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic failure

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (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

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (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 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Back pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Flank pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (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

Acute sinusitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bacteraemia

subjects affected / exposed

0 / 1 (0.00%)

1 / 1 (100.00%)

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Device related infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia bacteraemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 14 (7.14%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Meningitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

1 / 14 (7.14%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis acute

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (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 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

0 / 6 (0.00%)

0 / 14 (0.00%)

1 / 10 (10.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Septic shock

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

Urinary tract infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

1 / 8 (12.50%)

0 / 12 (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

Hypercalcaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperglycaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 18 (0.00%)

0 / 6 (0.00%)

0 / 14 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (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 / 1 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

1 / 18 (5.56%)

0 / 6 (0.00%)

1 / 14 (7.14%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 12 (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

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

Non-serious adverse events	QD 0.5 mg	QD 1 mg	QD 2 mg	QD 4 mg	QD 8 mg	QD 16 mg	QD 25 mg	QD 40 mg	Dose Expansion cohort - HNSCC	BID 15 mg	BID 10 mg	Dose Expansion cohort - GBM	Dose Expansion cohort - ES	Dose Expansion cohort - CRPC	Dose Expansion cohort - CLL/SLL	Dose Expansion cohort - BA/Food Effect
Total subjects affected by non serious adverse events
subjects affected / exposed	1 / 1 (100.00%)	1 / 1 (100.00%)	1 / 1 (100.00%)	3 / 4 (75.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	7 / 7 (100.00%)	6 / 6 (100.00%)	18 / 18 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	14 / 14 (100.00%)	10 / 10 (100.00%)	12 / 12 (100.00%)	8 / 8 (100.00%)	12 / 12 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	2
Melanocytic naevus
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tumour haemorrhage
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Tumour necrosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Tumour pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Vascular disorders
Arterial disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Deep vein thrombosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 14 (14.29%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	1	2	0	0	1	0	0	0	1
Flushing
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Haematoma
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Hot flush
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Hypertension
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hypotension
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	2
Orthostatic hypotension
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1
Pallor
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Peripheral coldness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	3 / 18 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 14 (7.14%)	4 / 10 (40.00%)	3 / 12 (25.00%)	2 / 8 (25.00%)	4 / 12 (33.33%)
occurrences all number	0	0	0	1	0	0	0	1	9	0	1	2	8	4	2	7
Chest discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	2
Chills
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	0	0	0	2	0	0	2	0	2	1	0	0	0	0
Cyst
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Early satiety
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Face oedema
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Facial pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Fatigue
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	6 / 7 (85.71%)	5 / 6 (83.33%)	11 / 18 (61.11%)	4 / 6 (66.67%)	3 / 6 (50.00%)	10 / 14 (71.43%)	4 / 10 (40.00%)	10 / 12 (83.33%)	1 / 8 (12.50%)	7 / 12 (58.33%)
occurrences all number	0	5	0	2	1	3	9	9	18	5	3	12	3	16	1	10
Gait disturbance
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 14 (14.29%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1
General physical health deterioration
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Influenza like illness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Mucosal inflammation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	2 / 6 (33.33%)	3 / 18 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	2 / 8 (25.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	1	2	6	1	0	0	0	1	3	1
Non-cardiac chest pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	2 / 10 (20.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	2	0	1	2
Oedema peripheral
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 7 (28.57%)	1 / 6 (16.67%)	2 / 18 (11.11%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 14 (7.14%)	0 / 10 (0.00%)	5 / 12 (41.67%)	2 / 8 (25.00%)	2 / 12 (16.67%)
occurrences all number	1	0	0	0	1	1	2	1	4	0	3	1	0	4	2	2
Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	0	1	0
Peripheral swelling
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2
Pyrexia
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 6 (0.00%)	5 / 18 (27.78%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 14 (14.29%)	1 / 10 (10.00%)	2 / 12 (16.67%)	5 / 8 (62.50%)	2 / 12 (16.67%)
occurrences all number	0	6	0	1	1	1	1	0	5	0	5	2	1	2	9	2
Swelling
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Temperature intolerance
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Tenderness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Social circumstances
HEARING IMPAIRMENT
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Reproductive system and breast disorders
Cervical polyp
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Gynaecomastia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Pelvic pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Penile pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Vaginal discharge
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (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 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Vulvovaginal swelling
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
DYSPNEA ON EXERTION
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Atelectasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Bronchial obstruction
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Bronchospasm
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Catarrh
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cough
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	2 / 18 (11.11%)	2 / 6 (33.33%)	2 / 6 (33.33%)	0 / 14 (0.00%)	3 / 10 (30.00%)	1 / 12 (8.33%)	3 / 8 (37.50%)	4 / 12 (33.33%)
occurrences all number	0	0	1	1	0	0	0	1	2	3	2	0	4	1	3	3
Dysphonia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0	1	0
Dyspnoea
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	2 / 4 (50.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 18 (11.11%)	3 / 6 (50.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	4 / 10 (40.00%)	3 / 12 (25.00%)	2 / 8 (25.00%)	5 / 12 (41.67%)
occurrences all number	0	2	0	2	0	2	0	0	6	6	1	0	6	3	2	6
Dyspnoea at rest
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Dyspnoea exertional
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	2 / 10 (20.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	2	0	0	2
Epistaxis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	2	0	0	1	0	0	0	0	0	1
Haemoptysis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Hiccups
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hypoxia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Increased bronchial secretion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Lung infiltration
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Nasal congestion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1	0	2	0	1	0
Nasal inflammation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1
Paranasal sinus discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Pharyngeal inflammation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pleuritic pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0
Pneumothorax
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (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 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 6 (50.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	4	0	0	1	0	0	0	1	0	1	0
Pulmonary embolism
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Pulmonary oedema
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Respiratory tract congestion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Rhinorrhoea
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	3 / 8 (37.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	5	0
Sputum discoloured
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1	0
Wheezing
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Psychiatric disorders
Abulia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Agitation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Anxiety
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 14 (14.29%)	2 / 10 (20.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	2	1	0	0	2
Bradyphrenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Confusional state
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 6 (33.33%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 14 (21.43%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	2	3	0	0	0	1
Depression
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 14 (14.29%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	2	0	0	0	3
Insomnia
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 14 (14.29%)	1 / 10 (10.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	1	0	0	1	0	1	1	1	0	0	3	1	1	0	1
Irritability
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Nervousness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Personality change
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Restlessness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Sleep disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	2 / 8 (25.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	3	0
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	2	0	0	0	0	0	0	0
Alanine aminotransferase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 14 (7.14%)	1 / 10 (10.00%)	3 / 12 (25.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	1	2	1	2	1	3	1	1
Amylase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 14 (7.14%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	2	0	1	0	1
Aspartate aminotransferase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 14 (7.14%)	2 / 10 (20.00%)	4 / 12 (33.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1	0	0	0	1	2	0	1	4	5	0	2
Bacterial test positive
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Blood albumin decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 14 (0.00%)	2 / 10 (20.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	2	0	0	1	2	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood cholesterol increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1
Blood creatinine increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 6 (0.00%)	1 / 18 (5.56%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	2	0	1	7	0	0	0	0	1	3
Blood insulin increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	2	0	0	3	0	0	0	0	1	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	1	1	0
Blood phosphorus increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Blood thyroid stimulating hormone decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood triglycerides increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Breath sounds abnormal
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
CD4 lymphocytes increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ejection fraction decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Eosinophil count increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	3	1	0	0	0
Glucose urine present
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Glycosylated haemoglobin increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	1	0	0	1	0	0	0	4	0	0	0	0	0	1
Insulin C-peptide increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	3 / 6 (50.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	1	4	0	0	2	0	0	0	0	0	0	0
International normalised ratio increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0
Lipase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 14 (7.14%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	1	0	3	0	1
Lymphocyte count decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	2 / 10 (20.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	1	0	0	0
Neutrophil count decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Platelet count decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Tandem gait test abnormal
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Thyroxine increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Transaminases increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	1
Weight decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	1 / 7 (14.29%)	1 / 6 (16.67%)	7 / 18 (38.89%)	3 / 6 (50.00%)	1 / 6 (16.67%)	1 / 14 (7.14%)	2 / 10 (20.00%)	3 / 12 (25.00%)	4 / 8 (50.00%)	5 / 12 (41.67%)
occurrences all number	0	0	0	0	0	3	1	1	9	4	1	1	2	5	6	7
Weight increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
White blood cell count decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	1	1	0	0	0
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Contusion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Ear injury
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Fall
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	1	0	1	0	1
Foreign body in eye
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Head injury
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Inappropriate schedule of product administration
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Injury corneal
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Muscle strain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Overdose
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0
Post procedural discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (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	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 14 (14.29%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Skin laceration
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Skin wound
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Congenital, familial and genetic disorders
Primary immunodeficiency syndrome
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Cardiomyopathy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Palpitations
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0
Supraventricular tachycardia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
MITRAL VALVE DISEASE
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Nervous system disorders
Aphasia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Apraxia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ataxia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Disturbance in attention
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Dizziness
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	2 / 18 (11.11%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 14 (14.29%)	0 / 10 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	3 / 12 (25.00%)
occurrences all number	0	2	0	1	0	0	1	1	2	0	1	2	0	2	1	4
Dysaesthesia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dysarthria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (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 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	1	1	0	0	0	2	0	2	1	1
Facial neuralgia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Facial paralysis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Formication
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Headache
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	1 / 7 (14.29%)	0 / 6 (0.00%)	1 / 18 (5.56%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 14 (14.29%)	2 / 10 (20.00%)	2 / 12 (16.67%)	2 / 8 (25.00%)	2 / 12 (16.67%)
occurrences all number	0	1	0	0	0	3	1	0	0	1	4	2	2	2	2	2
Hemiparesis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 14 (14.29%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Hyperaesthesia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hypersomnia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hypoaesthesia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 14 (7.14%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	2	0	0	1	1	0	1	0	0
Lethargy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Memory impairment
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 14 (14.29%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	2	0	0	1	0
Neuralgia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Neuropathy peripheral
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	1	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Neurotoxicity
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Paraesthesia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	3 / 12 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	3
Seizure
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 14 (14.29%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Sensory disturbance
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Sensory loss
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	3 / 10 (30.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	3	0	0	1
Syncope
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	2
Taste disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	1 / 6 (16.67%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0	1	0	0	0	0	0	0
Tremor
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	1	0	1	0	0	0	0	0
Trigeminal nerve paresis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Vocal cord paralysis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	5 / 18 (27.78%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 14 (14.29%)	5 / 10 (50.00%)	1 / 12 (8.33%)	2 / 8 (25.00%)	3 / 12 (25.00%)
occurrences all number	0	0	0	3	0	1	0	0	9	0	0	1	2	4	3	7
Eosinophilia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Iron deficiency anaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Leukocytosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	3
Lymphopenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	3 / 8 (37.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0
Normocytic anaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Thrombocytopenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	2 / 12 (16.67%)	3 / 8 (37.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	3	1	0	0	0	0	0	2	2	3	0
Ear and labyrinth disorders
Deafness bilateral
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Ear discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Ear pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Eustachian tube disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Hypoacusis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Tinnitus
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Vertigo positional
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Eye disorders
Blepharitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Blindness unilateral
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cataract
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Chorioretinal disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Diplopia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dry eye
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Eye disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Eye pruritus
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
Eyelid ptosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1
Scleral hyperaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Strabismus
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vision blurred
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0
Visual impairment
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 14 (14.29%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	2	0	0	0	2
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	1	0	0	1	0	0	0	0	0	1	0	0	1
Abdominal distension
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	2
Abdominal pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 7 (28.57%)	0 / 6 (0.00%)	2 / 18 (11.11%)	1 / 6 (16.67%)	2 / 6 (33.33%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	4 / 12 (33.33%)
occurrences all number	0	0	0	1	0	3	2	0	2	1	3	1	0	0	0	4
Abdominal pain lower
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Abdominal pain upper
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	1 / 18 (5.56%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	1	0	1	0	1	1	0	0	0	0	0	1
Abdominal tenderness
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Anal incontinence
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Anal inflammation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Anorectal discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Aphthous ulcer
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0
Breath odour
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Colitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Constipation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	2 / 7 (28.57%)	1 / 6 (16.67%)	3 / 18 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 14 (14.29%)	3 / 10 (30.00%)	3 / 12 (25.00%)	1 / 8 (12.50%)	4 / 12 (33.33%)
occurrences all number	0	0	0	0	2	2	2	1	3	0	0	2	6	2	1	5
Dental caries
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Diarrhoea
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)	4 / 18 (22.22%)	3 / 6 (50.00%)	3 / 6 (50.00%)	5 / 14 (35.71%)	4 / 10 (40.00%)	3 / 12 (25.00%)	4 / 8 (50.00%)	7 / 12 (58.33%)
occurrences all number	0	1	0	0	2	0	4	0	5	6	10	9	8	5	7	13
Dry mouth
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 14 (14.29%)	3 / 10 (30.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	1	0	0	0	1	1	0	0	0	1	0	2	3	2	0	2
Dyspepsia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 7 (42.86%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	3	0	0	0	1	0	0	4	2	1
Dysphagia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 6 (33.33%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	2	0	0	0	0	0	1	0
Flatulence
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Frequent bowel movements
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	1
Gingival bleeding
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Glossodynia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0
Haemorrhoids
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	1
Nausea
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	4 / 6 (66.67%)	3 / 6 (50.00%)	4 / 7 (57.14%)	4 / 6 (66.67%)	7 / 18 (38.89%)	2 / 6 (33.33%)	3 / 6 (50.00%)	4 / 14 (28.57%)	5 / 10 (50.00%)	4 / 12 (33.33%)	3 / 8 (37.50%)	10 / 12 (83.33%)
occurrences all number	0	0	0	0	5	4	7	9	7	2	5	4	6	7	3	10
Odynophagia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Oral pain
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	1	0	0	0	0	4	0	0	0	0	0	0	1	0	1
Rectal discharge
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Rectal haemorrhage
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 7 (42.86%)	3 / 6 (50.00%)	1 / 18 (5.56%)	2 / 6 (33.33%)	1 / 6 (16.67%)	2 / 14 (14.29%)	2 / 10 (20.00%)	4 / 12 (33.33%)	1 / 8 (12.50%)	4 / 12 (33.33%)
occurrences all number	0	0	0	0	0	1	8	5	2	5	2	3	3	5	1	9
Toothache
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	1	1	1
Vomiting
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 4 (50.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	5 / 7 (71.43%)	6 / 6 (100.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	4 / 6 (66.67%)	2 / 14 (14.29%)	3 / 10 (30.00%)	3 / 12 (25.00%)	0 / 8 (0.00%)	6 / 12 (50.00%)
occurrences all number	0	0	0	3	4	4	9	9	1	0	9	2	3	4	0	10
Hepatobiliary disorders
Bile duct stenosis
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Biliary dilatation
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hyperbilirubinaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Jaundice
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Jaundice cholestatic
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Skin and subcutaneous tissue disorders
PRURITIC LESIONS
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Acne
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Alopecia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0
Blister
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Dermal cyst
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Dermatitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	3 / 14 (21.43%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	7	6	0	1	1
Dry skin
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	3 / 12 (25.00%)
occurrences all number	0	1	0	0	0	0	0	0	2	0	0	0	1	2	0	3
Eczema
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	3	0	0	0	2	0
Erythema nodosum
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Ingrowing nail
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0
Intertrigo
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Nail disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0
Night sweats
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	1	0	0	0	2	0
Nodular rash
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Onychalgia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Onychoclasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Pain of skin
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Photosensitivity reaction
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 14 (0.00%)	1 / 10 (10.00%)	3 / 12 (25.00%)	1 / 8 (12.50%)	3 / 12 (25.00%)
occurrences all number	0	1	0	0	0	1	1	0	0	1	2	0	2	3	1	5
Pruritus generalised
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	3 / 12 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	3
Psoriasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	6	0	0	0	0	0	0	0	1	0
Purpura
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Rash
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	4 / 7 (57.14%)	2 / 6 (33.33%)	2 / 18 (11.11%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 14 (14.29%)	1 / 10 (10.00%)	4 / 12 (33.33%)	3 / 8 (37.50%)	3 / 12 (25.00%)
occurrences all number	0	0	0	0	0	1	8	2	2	0	2	2	1	11	4	5
Rash erythematous
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Rash generalised
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	1
Rash macular
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Rash maculo-papular
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	1 / 6 (16.67%)	2 / 18 (11.11%)	2 / 6 (33.33%)	1 / 6 (16.67%)	2 / 14 (14.29%)	3 / 10 (30.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	2	0	0	0	1	4	1	7	7	3	2	5	2	0	2
Rash papular
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0
Rash pruritic
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 14 (7.14%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	9	2	1	0	1	0	0
Scab
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin discolouration
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Skin fissures
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0
Skin irritation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Skin lesion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	2	0	0	0
Skin mass
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Skin ulcer haemorrhage
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Toxic skin eruption
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0
Urticaria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0
Renal and urinary disorders
Chronic kidney disease
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0
Dysuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 14 (0.00%)	2 / 10 (20.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	1	0	1	0	0	1
Glycosuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Haematuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Incontinence
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Leukocyturia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Nocturia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Pollakiuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	3 / 12 (25.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	5	0	0
Proteinuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	2 / 8 (25.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	0	0	3	1	4	0
Renal atrophy
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Renal vein thrombosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Urinary hesitation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Urinary incontinence
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	1	0	0
Urinary retention
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	3 / 6 (50.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	0	0	0	2	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	3 / 12 (25.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	1	0	1	0	0	5	0	1	0	0	0	0	7	1	1
Back pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 14 (7.14%)	0 / 10 (0.00%)	3 / 12 (25.00%)	0 / 8 (0.00%)	3 / 12 (25.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	1	1	0	6	0	3
Bone pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Coccydynia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Flank pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0
Groin pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Intervertebral disc protrusion
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Joint stiffness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Joint swelling
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Muscle spasms
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 14 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	2 / 8 (25.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	3	1	0	1	0	0	1	3	0	0	2	5	2
Muscle twitching
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Muscular weakness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	2 / 10 (20.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0	0	2	0	0	1
Musculoskeletal discomfort
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1
Musculoskeletal stiffness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	1	0	0	0	0	0	0
Myalgia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	4	1	0	3	0	0	0
Neck pain
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Pain in extremity
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 7 (28.57%)	1 / 6 (16.67%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 14 (14.29%)	1 / 10 (10.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	2	2	0	0	1	2	3	0	0	1
Pain in jaw
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Spondylitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Temporomandibular joint syndrome
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Trismus
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Infections and infestations
Bacteraemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Bronchitis
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	1	0	2	0
Cellulitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Cystitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Eye infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Folliculitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0
Fungal skin infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (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 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Herpes zoster
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	2 / 12 (16.67%)
occurrences all number	0	1	0	0	0	0	0	0	1	1	2	0	0	0	2	2
Kidney infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Laryngitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Lung infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Mastoiditis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Nasal vestibulitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Nasopharyngitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Onychomycosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	1
Oral candidiasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	1
Oral herpes
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	2	0
Otitis externa
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Otitis media
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Paronychia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0	1	0
Pneumonia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	3
Postoperative wound infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Rash pustular
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Respiratory tract infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0	1	0
Sepsis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Skin infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Staphylococcal infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Tooth abscess
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Tooth infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	2
Urinary tract infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	0 / 10 (0.00%)	1 / 12 (8.33%)	2 / 8 (25.00%)	3 / 12 (25.00%)
occurrences all number	0	0	0	0	0	0	1	0	3	0	0	1	0	1	4	2
Urinary tract infection bacterial
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Viral infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Wound infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Metabolism and nutrition disorders
Cachexia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Decreased appetite
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	5 / 7 (71.43%)	4 / 6 (66.67%)	8 / 18 (44.44%)	2 / 6 (33.33%)	2 / 6 (33.33%)	2 / 14 (14.29%)	5 / 10 (50.00%)	8 / 12 (66.67%)	2 / 8 (25.00%)	8 / 12 (66.67%)
occurrences all number	0	1	0	0	2	2	5	3	9	2	2	3	7	10	2	8
Dehydration
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	2 / 18 (11.11%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	4 / 12 (33.33%)
occurrences all number	1	0	0	1	0	0	0	1	2	1	0	0	0	3	0	5
Failure to thrive
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Hypercholesterolaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	8	0	0	0	0	0	0
Hyperglycaemia
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 1 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	3 / 6 (50.00%)	2 / 7 (28.57%)	1 / 6 (16.67%)	4 / 18 (22.22%)	2 / 6 (33.33%)	1 / 6 (16.67%)	6 / 14 (42.86%)	3 / 10 (30.00%)	4 / 12 (33.33%)	1 / 8 (12.50%)	3 / 12 (25.00%)
occurrences all number	0	1	0	2	0	3	2	1	4	9	1	19	4	8	7	4
Hyperkalaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Hypertriglyceridaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	2 / 18 (11.11%)	3 / 6 (50.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	2 / 10 (20.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	2	21	0	0	2	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 18 (5.56%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hypervolaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hypoalbuminaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	2 / 10 (20.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	2	0	0	1	0	0	0	2	0	0	2
Hypocalcaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 14 (7.14%)	1 / 10 (10.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	1	0	0	0
Hypoglycaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hypokalaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	3 / 12 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	4
Hypomagnesaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 18 (11.11%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	3 / 12 (25.00%)
occurrences all number	0	0	0	0	1	0	0	0	2	0	0	0	0	0	0	2
Hyponatraemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 7 (0.00%)	0 / 6 (0.00%)	4 / 18 (22.22%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	2	0	0	3	0	0	0	1	0	0	2
Hypophosphataemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	1 / 6 (16.67%)	1 / 18 (5.56%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 14 (14.29%)	1 / 10 (10.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	2	1	0	1	0	5	3	1	0	1
Increased appetite
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Vitamin D deficiency
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 18 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 14 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

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Were there any global substantial amendments to the protocol? No

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants Experiencing Dose-Limiting Toxicity (DLT)

Primary: Number of Participants Experiencing Dose-Limiting Toxicity (DLT)

Primary: Maximum Observed Concentration (Cmax)

Primary: Maximum Observed Concentration (Cmax)

Primary: Maximum Observed Concentration (Cmax) - BA/Food Effect Cohort

Primary: Maximum Observed Concentration (Cmax) - BA/Food Effect Cohort

Primary: Area Under the Concentration-Time Curve (AUC)

Primary: Area Under the Concentration-Time Curve (AUC)

Primary: Area Under the Concentration-Time Curve (AUCinf) - BA/Food Effect Cohort

Primary: Area Under the Concentration-Time Curve (AUCinf) - BA/Food Effect Cohort

Primary: Time to Maximum Concentration (Tmax)

Primary: Time to Maximum Concentration (Tmax)

Primary: Time to Maximum Concentration (Tmax) - BA/Food Effect Cohort

Primary: Time to Maximum Concentration (Tmax) - BA/Food Effect Cohort

Primary: Terminal Half-Life (t1/2)

Primary: Terminal Half-Life (t1/2)

Primary: Terminal Half-Life (t1/2) - BA/Food Effect Cohort

Primary: Terminal Half-Life (t1/2) - BA/Food Effect Cohort

Primary: Apparent Total Body Clearance (CL/F)

Primary: Apparent Total Body Clearance (CL/F)

Primary: Apparent Total Body Clearance (CL/F) - BA/Food Effect Cohort

Primary: Apparent Total Body Clearance (CL/F) - BA/Food Effect Cohort

Primary: Apparent Volume of Distribution (Vz/F)

Primary: Apparent Volume of Distribution (Vz/F)

Primary: Apparent Volume of Distribution (Vz/F) - BA/Food Effect Cohort

Primary: Apparent Volume of Distribution (Vz/F) - BA/Food Effect Cohort

Primary: Drug Accumulation Ratio (Rac)

Primary: Drug Accumulation Ratio (Rac)

Secondary: Change from Baseline in Blood Levels of Phosphorylated 4E-Binding Protein 1 (pE4-BP1)

Secondary: Change from Baseline in Blood Levels of Phosphorylated 4E-Binding Protein 1 (pE4-BP1)

Secondary: Change from Baseline in the Percent Ratio of Phosphorylated AKT (p-AKT)/ Total AKT

Secondary: Change from Baseline in the Percent Ratio of Phosphorylated AKT (p-AKT)/ Total AKT

Secondary: Change from Baseline in the Levels of UV-Stimulated phosphorylated DNA-dependent Protein Kinase (pDNA-PK)

Secondary: Change from Baseline in the Levels of UV-Stimulated phosphorylated DNA-dependent Protein Kinase (pDNA-PK)

Secondary: Objective Response Rate (ORR)

Secondary: Objective Response Rate (ORR)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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