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Clinical Trial Results:
A RANDOMIZED PHASE 2 TRIAL OF AXITINIB AND TRC105 VERSUS AXITINIB ALONE (INCLUDING A LEAD-IN PHASE 1B DOSE-ESCALATION PORTION) IN PATIENTS WITH ADVANCED OR METASTATIC RENAL CELL CARCINOMA

Summary
EudraCT number	2015-003436-13
Trial protocol	HU GB PL CZ
Global end of trial date	12 Jun 2019

Results information
Results version number	v1(current)
This version publication date	02 Jun 2021
First version publication date	02 Jun 2021
Other versions

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

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Trial information

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Sponsor protocol code

105RC101

ISRCTN number

US NCT number

NCT01806064

WHO universal trial number (UTN)

Sponsor organisation name

TRACON Pharmaceuticals, Inc.

Sponsor organisation address

4350 La Jolla Village Drive, Suite 800, San Diego, United States, 92010

Public contact

Study Manager, TRACON Pharmaceuticals Inc., +1 8585500780, clinicaltrials@traconpharma.com

Scientific contact

Study Manager, TRACON Pharmaceuticals Inc., +1 8585500780, clinicaltrials@traconpharma.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

12 Jun 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

21 Dec 2018

Global end of trial reached?

Yes

Global end of trial date

12 Jun 2019

Was the trial ended prematurely?

Main objective of the trial

Phase 1b: To evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose axitinib in patients with renal cell carcinoma. Phase 2: To estimate the PFS of patients with advanced or metastatic RCC by RECIST 1.1 criteria in patients treated with axitinib and TRC105 compared to those treated with axitinib alone, following failure of one prior VEGF inhibitor

Protection of trial subjects

Safety parameters were reviewed by a chartered Safety Review Team that reviewed data for all TRC105 studies quarterly and a chartered Data Monitoring Committee (DMC) that periodically reviewed accumulating safety and efficacy data from this study. An interim analysis for futility was conducted by the DMC when 55 events occurred. At the interim analysis, the conditional power based on the observed hazard ratio was estimated. If the conditional power was less than 25%, the DMC could recommend the sponsor that the study be terminated for futility. This interim analysis did not consider the possibility of early termination on the basis of superior efficacy.

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Dec 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 1

Country: Number of subjects enrolled

Czechia: 13

Country: Number of subjects enrolled

Hungary: 21

Country: Number of subjects enrolled

United States: 138

Worldwide total number of subjects

173

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

23 patients enrolled in phase 1b portion. 150 patients randomized in the phase 2 portion.

Screening details

Patients with advanced or metastatic renal cell carcinoma.

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

P2 Arm A: 5 mg Axitinib BID

Arm description

Phase 2 Arm A: 5 mg Axitinib twice daily

Arm type

Active comparator

Investigational medicinal product name

Axitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

1mg and 5mg tablets

P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Arm description

Phase 2 Arm B: 10 mg/kg TRC105 weekly + 5 mg Axitinib twice daily

Arm type

Experimental

Investigational medicinal product name

Axitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

5mg tablets twice daily

Investigational medicinal product name

TRC 105

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

10mg/kg Weekly

P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Arm description

Phase 1b Dose Level 1: 8 mg/kg TRC105 weekly in combination with 5 mg Axitinib twice daily

Arm type

Experimental

Investigational medicinal product name

Axitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

5mg tablets twice daily

Investigational medicinal product name

TRC 105

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

8mg/kg Weekly

P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Arm description

Phase 1b Dose Level 2: 10 mg/kg TRC105 weekly in combination with 5 mg Axitinib twice daily

Arm type

Experimental

Investigational medicinal product name

Axitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

5mg tablets twice daily

Investigational medicinal product name

TRC 105

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

10mg/kg Weekly

P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID

Arm description

Phase 1b Dose Level 3: 10 mg/kg TRC105 weekly during cycle 1 then 15 mg/kg TRC105 every two weeks beginning in cycle 2 in combination with 5 mg Axitinib twice daily

Arm type

Experimental

Investigational medicinal product name

Axitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

5mg tablets twice daily

Investigational medicinal product name

TRC 105

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

10 mg/kg TRC105 weekly during cycle 1 then 15 mg/kg TRC105 every two weeks beginning in cycle 2

Number of subjects in period 1	P2 Arm A: 5 mg Axitinib BID	P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID
Started	75	75	3	15	5
Completed	74	73	3	15	5
Not completed	1	2	0	0	0
Randomized not enrolled	1	2	-	-	-

Baseline characteristics

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Reporting group title

P2 Arm A: 5 mg Axitinib BID

Reporting group description

Phase 2 Arm A: 5 mg Axitinib twice daily

Reporting group title

P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Reporting group description

Phase 2 Arm B: 10 mg/kg TRC105 weekly + 5 mg Axitinib twice daily

Reporting group title

P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Reporting group description

Phase 1b Dose Level 1: 8 mg/kg TRC105 weekly in combination with 5 mg Axitinib twice daily

Reporting group title

P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Reporting group description

Phase 1b Dose Level 2: 10 mg/kg TRC105 weekly in combination with 5 mg Axitinib twice daily

Reporting group title

P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID

Reporting group description

Phase 1b Dose Level 3: 10 mg/kg TRC105 weekly during cycle 1 then 15 mg/kg TRC105 every two weeks beginning in cycle 2 in combination with 5 mg Axitinib twice daily

Reporting group values	P2 Arm A: 5 mg Axitinib BID	P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID	Total
Number of subjects	75	75	3	15	5	173
Age categorical
All patients who received at least a portion of a dose of TRC105 or axitinib
Units: Subjects
Adults (18-64 years)	35	43	0	13	2	93
From 65-84 years	40	32	3	2	3	80
Gender categorical
All patients who received at least a portion of a dose of TRC105 or axitinib
Units: Subjects
Female	18	26	0	2	2	48
Male	57	49	3	13	3	125
Race/Ethnicity
All patients who received at least a portion of a dose of TRC105 or axitinib
Units: Subjects
Caucasian	70	71	3	12	5	161
Hispanic or Latino	5	1	0	3	0	9
American Indian or Alaska Native	0	2	0	0	0	2
Native Hawaiian or other Pacific Islander	0	1	0	0	0	1
Region of Enrollment
All patients who received at least a portion of a dose of TRC105 or axitinib
Units: Subjects
Hungary	11	10	0	0	0	21
United States	56	59	3	15	5	138
Czechia	8	5	0	0	0	13
United Kingdom	0	1	0	0	0	1

End points

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Reporting group title

P2 Arm A: 5 mg Axitinib BID

Reporting group description

Phase 2 Arm A: 5 mg Axitinib twice daily

Reporting group title

P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Reporting group description

Phase 2 Arm B: 10 mg/kg TRC105 weekly + 5 mg Axitinib twice daily

Reporting group title

P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Reporting group description

Phase 1b Dose Level 1: 8 mg/kg TRC105 weekly in combination with 5 mg Axitinib twice daily

Reporting group title

P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Reporting group description

Phase 1b Dose Level 2: 10 mg/kg TRC105 weekly in combination with 5 mg Axitinib twice daily

Reporting group title

P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID

Reporting group description

Phase 1b Dose Level 3: 10 mg/kg TRC105 weekly during cycle 1 then 15 mg/kg TRC105 every two weeks beginning in cycle 2 in combination with 5 mg Axitinib twice daily

Primary: Phase 1b: Number of Patients with DLT

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End point title

Phase 1b: Number of Patients with DLT ^[1] ^[2]

End point description

Phase 1b: For dose limiting toxicity (DLT) evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0). Patients who discontinued the study prior to completing the DLT evaluation period were not evaluable.

End point type

Primary

End point timeframe

12 Months

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: In Phase 1b there were no dose limiting toxicities.
[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: For Phase 2 the number of patients with DLT was not measured.

End point values	P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID
Number of subjects analysed	3	15	5
Units: Participants	0	0	0

No statistical analyses for this end point

Primary: Phase 2: Progression free survival (PFS) of patients with RCC

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End point title

Phase 2: Progression free survival (PFS) of patients with RCC ^[3]

End point description

Median progression free survival (PFS) of patients with advanced or metastatic RCC by RECIST 1.1. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. For Phase 2 all randomized patients were included in the efficacy population.

End point type

Primary

End point timeframe

15 Months

Notes
[3] - 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: PFS was not measured in Phase 1b.

End point values	P2 Arm A: 5 mg Axitinib BID	P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID
Number of subjects analysed	75	75
Units: Months
median (confidence interval 95%)	11.4 (5.8 to 13)	6.7 (5.6 to 13.1)

Comparative

Statistical analysis description

PFS comparison between Arm A and Arm B.

Comparison groups

P2 Arm A: 5 mg Axitinib BID v P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

superiority

P-value

≤ 0.1

Method

Logrank

Confidence interval

Secondary: Phase 1b & 2: Response Rate of patients with RCC

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End point title

Phase 1b & 2: Response Rate of patients with RCC

End point description

Number of patients with partial response (PR) or complete response (CR) by RECIST 1.1 criteria. Per Response Evaluation Criteria in Solid Tumors Criteria RECIST v1.1 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. For Phase 1b patients with screening and at least 1 on study scan were included in the efficacy population. For Phase 2 all randomized patients were included in the efficacy population. Patients without a baseline scan and at least 1 on study scan were excluded from analysis.

End point type

Secondary

End point timeframe

15 Months

End point values	P2 Arm A: 5 mg Axitinib BID	P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID
Number of subjects analysed	75	75	3	14	5
Units: Participants	22	23	0	5	0

Comparative

Statistical analysis description

Response rate by RECIST 1.1 criteria.

Comparison groups

P2 Arm A: 5 mg Axitinib BID v P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID v P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID v P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID v P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID

Number of subjects included in analysis

172

Analysis specification

Pre-specified

Analysis type

other ^[4]

P-value

≤ 0.1

Method

Chi-squared test

Confidence interval

Notes
[4] - Response rate by RECIST in Phase 1b patients (descriptive) and in Phase 2 patients (superiority).

Secondary: Phase 2: Overall Response Rate of patients with RCC by Choi

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End point title

Phase 2: Overall Response Rate of patients with RCC by Choi ^[5]

End point description

Overall response (OR) rate is the number of patients with partial response (PR) or complete response (CR) by Choi Criteria. Per Choi criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), A decrease in size ≥ 10% or a decrease in tumor attenuation (Houndsfield units) ≥ 15% on CT and no new lesions; Overall Response (OR) = CR + PR. For Phase 2 all randomized patients were included in the efficacy population. Patients without a baseline scan and at least 1 on study scan were excluded from analysis.

End point type

Secondary

End point timeframe

15 Months

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: For Phase 1b Overall Response Rate of patients with RCC by Choi was not measured.

End point values	P2 Arm A: 5 mg Axitinib BID	P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID
Number of subjects analysed	75	75
Units: Participants	50	50

Comparative

Statistical analysis description

The primary endpoint for efficacy is PFS.

Comparison groups

P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID v P2 Arm A: 5 mg Axitinib BID

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

superiority

P-value

≤ 0.1 ^[6]

Method

Chi-square

Confidence interval

Notes
[6] - One-sided test

Secondary: Phase 1b & 2: Trough concentrations of TRC105 by Dose Level in Phase 1b

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End point title

Phase 1b & 2: Trough concentrations of TRC105 by Dose Level in Phase 1b ^[7]

End point description

Trough Serum TRC105 concentrations at steady state (cycle 2 day 15) were measured using validated ELISA methods. In Phase 1b patients with a predose sample collected at cycle 2 day 15 were averaged. Patients who missed a dose of TRC105 prior to cycle 2 day 15 were excluded from the analysis. Additional Phase 1b PK analysis beyond steady state concentration at cycle 2 day 15 were not performed. Samples collected in the phase 2 portion of the study were not analyzed.

End point type

Secondary

End point timeframe

2.5 months (cycle 2 day 15)

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study was terminated due to lack of efficacy and samples collected in the phase 2 portion of the study were not analyzed.

End point values	P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID
Number of subjects analysed	3	13	5
Units: ng/mL
arithmetic mean (standard deviation)	27650 ± 39103	140022 ± 45403.1	54375 ± 23546.5

No statistical analyses for this end point

Secondary: Phase 1b & 2: Number of patients with development of immunogenicity antibodies.

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End point title

Phase 1b & 2: Number of patients with development of immunogenicity antibodies. ^[8]

End point description

Anti-product antibody concentration were measured using validated ELISA methods. Patients must have had a baseline and on study assessment of immunogenicity and their baseline must have been negative. Samples collected in the phase 2 portion of the study were not analyzed.

End point type

Secondary

End point timeframe

12 Months

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The study was terminated early due to lack of efficacy and samples collected in the phase 2 portion of the study were not analyzed.

End point values	P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID
Number of subjects analysed	3	5	5
Units: Participants	1	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

2 years, 6 months. Only patients who received at least a portion of a dose of TRC105 and/or Axitinib have been included in the analysis population.

Adverse event reporting additional description

Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

4.0

Reporting group title

P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Reporting group description

Phase 1b Dose Level 1: 8 mg/kg TRC105 weekly in combination with 5 mg Axitinib twice daily

Reporting group title

P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Reporting group description

Phase 1b Dose Level 2: 10 mg/kg TRC105 weekly in combination with 5 mg Axitinib twice daily

Reporting group title

P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID

Reporting group description

Phase 1b Dose Level 3: 10 mg/kg TRC105 weekly during cycle 1 then 15 mg/kg TRC105 every two weeks beginning in cycle 2 in combination with 5 mg Axitinib twice daily

Reporting group title

P2 Arm A: 5 mg Axitinib BID

Reporting group description

Phase 2 Arm A: 5 mg Axitinib twice daily

Reporting group title

P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID

Reporting group description

Phase 2 Arm B: 10 mg/kg TRC105 weekly + 5 mg Axitinib twice daily

Serious adverse events	P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID	P2 Arm A: 5 mg Axitinib BID	P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 3 (33.33%)	4 / 15 (26.67%)	3 / 5 (60.00%)	27 / 74 (36.49%)	28 / 73 (38.36%)
number of deaths (all causes)	0	1	0	3	3
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial Neoplasm
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep Vein Thrombosis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Disease Progression
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	4 / 73 (5.48%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 4
Fatigue
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Multi-organ Failure
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Pelvic Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural Effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Vomiting
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Confusional State
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Infusion Related Reaction
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femur Fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal Fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute Heart Failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Myocardial Infarction
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Encephalopathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hemiparesis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage Intracranial
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Migraine
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paraparesis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Posterior Reversible Encephalopathy Syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	5 / 73 (6.85%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	4 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal Vein Occlusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gallbladder Perforation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	1 / 5 (20.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal Ulcer Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colonic Perforation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal Perforation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower Gastrointestinal Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Liver Injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute Kidney Injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Musculoskeletal and connective tissue disorders
Back Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscular Weakness
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Biliary Tract Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium Difficile Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium Difficile Colitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterococcal Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	2 / 5 (40.00%)	0 / 74 (0.00%)	3 / 73 (4.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	3 / 3	0 / 0	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	P1b: 8 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID	P1b: 10 mg/kg Wkly/15 mg/kg q2wks TRC105 + 5 mg Axitinib BID	P2 Arm A: 5 mg Axitinib BID	P2 Arm B: 10 mg/kg TRC105 Wkly + 5 mg Axitinib BID
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	15 / 15 (100.00%)	5 / 5 (100.00%)	71 / 74 (95.95%)	72 / 73 (98.63%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	3 / 73 (4.11%)
occurrences all number	0	0	0	0	3
Benign Neoplasm
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Breast Cancer
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Skin Papilloma
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Vascular disorders
Aortic Aneurysm
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Arteriosclerosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Deep Vein Thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0
Embolism
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Flushing
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	7 / 73 (9.59%)
occurrences all number	1	0	0	0	8
Haematoma
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Hot Flush
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	4
Hyperaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Hypertension
subjects affected / exposed	2 / 3 (66.67%)	4 / 15 (26.67%)	4 / 5 (80.00%)	33 / 74 (44.59%)	26 / 73 (35.62%)
occurrences all number	5	8	6	61	47
Hypotension
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)	2 / 74 (2.70%)	7 / 73 (9.59%)
occurrences all number	0	1	1	2	11
Orthostatic Hypotension
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Thrombophlebitis Superficial
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Surgical and medical procedures
Colostomy
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Tooth Extraction
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	2
Preventive Surgery
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	3 / 3 (100.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	9 / 74 (12.16%)	6 / 73 (8.22%)
occurrences all number	5	3	0	9	8
Catheter Site Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Catheter Site Swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Chest Discomfort
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	1	0	1	0
Chest Pain
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	4 / 74 (5.41%)	1 / 73 (1.37%)
occurrences all number	0	4	0	6	1
Chills
subjects affected / exposed	3 / 3 (100.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)	7 / 74 (9.46%)	11 / 73 (15.07%)
occurrences all number	4	1	1	9	13
Drug Intolerance
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Facial Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Fatigue
subjects affected / exposed	3 / 3 (100.00%)	9 / 15 (60.00%)	4 / 5 (80.00%)	40 / 74 (54.05%)	42 / 73 (57.53%)
occurrences all number	4	28	6	75	72
Feeling Cold
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	2	0	0	1
Feeling Hot
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
General Physical Health Deterioration
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Influenza Like Illness
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	3 / 74 (4.05%)	2 / 73 (2.74%)
occurrences all number	0	1	0	3	3
Infusion Site Erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Infusion Site Extravasation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Injection Site Erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Injection Site Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Injection Site Mass
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Local Swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Malaise
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	1 / 5 (20.00%)	4 / 74 (5.41%)	3 / 73 (4.11%)
occurrences all number	1	0	1	4	3
Medical Device Site Bruise
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Mucosal Inflammation
subjects affected / exposed	1 / 3 (33.33%)	7 / 15 (46.67%)	0 / 5 (0.00%)	6 / 74 (8.11%)	10 / 73 (13.70%)
occurrences all number	1	9	0	9	11
Non-Cardiac Chest Pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	4 / 74 (5.41%)	3 / 73 (4.11%)
occurrences all number	0	1	0	5	4
Oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	2
Oedema Peripheral
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	5 / 74 (6.76%)	5 / 73 (6.85%)
occurrences all number	0	1	0	12	6
Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	2 / 73 (2.74%)
occurrences all number	0	0	0	2	2
Pyrexia
subjects affected / exposed	2 / 3 (66.67%)	4 / 15 (26.67%)	1 / 5 (20.00%)	4 / 74 (5.41%)	10 / 73 (13.70%)
occurrences all number	8	5	1	4	10
Temperature Intolerance
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Thirst
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Gait Disturbance
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	2	0	0	0	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Seasonal Allergy
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Reproductive system and breast disorders
Breast Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	2
Erectile Dysfunction
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Genital Discharge
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Gynaecomastia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Nipple Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Pelvic Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	2
Prostatic Obstruction
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Scrotal Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Vaginal Lesion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Vulvovaginal Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Choking Sensation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Cough
subjects affected / exposed	1 / 3 (33.33%)	5 / 15 (33.33%)	1 / 5 (20.00%)	15 / 74 (20.27%)	14 / 73 (19.18%)
occurrences all number	1	6	1	24	18
Dry Throat
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Dysphonia
subjects affected / exposed	1 / 3 (33.33%)	6 / 15 (40.00%)	3 / 5 (60.00%)	27 / 74 (36.49%)	19 / 73 (26.03%)
occurrences all number	1	13	3	34	21
Dyspnoea
subjects affected / exposed	1 / 3 (33.33%)	1 / 15 (6.67%)	0 / 5 (0.00%)	10 / 74 (13.51%)	12 / 73 (16.44%)
occurrences all number	1	1	0	18	15
Dyspnoea Exertional
subjects affected / exposed	1 / 3 (33.33%)	2 / 15 (13.33%)	0 / 5 (0.00%)	3 / 74 (4.05%)	3 / 73 (4.11%)
occurrences all number	4	2	0	4	3
Epistaxis
subjects affected / exposed	2 / 3 (66.67%)	13 / 15 (86.67%)	5 / 5 (100.00%)	5 / 74 (6.76%)	47 / 73 (64.38%)
occurrences all number	2	23	6	6	68
Haemoptysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	2
Hiccups
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	1	0	0	1	0
Hypoxia
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	1 / 74 (1.35%)	3 / 73 (4.11%)
occurrences all number	0	2	0	1	6
Increased Upper Airway Secretion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Nasal Congestion
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	4 / 74 (5.41%)	6 / 73 (8.22%)
occurrences all number	0	1	0	5	6
Nasal Dryness
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	2
Nasal Septum Disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Nasal Septum Perforation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Nasal Septum Ulceration
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Nasal Ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Oropharyngeal Pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	6 / 74 (8.11%)	13 / 73 (17.81%)
occurrences all number	0	1	0	7	14
Pleural Effusion
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	1	1	0	3
Productive Cough
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	3 / 74 (4.05%)	4 / 73 (5.48%)
occurrences all number	1	0	0	3	6
Pulmonary Embolism
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	1	1	0
Respiratory Tract Congestion
subjects affected / exposed	1 / 3 (33.33%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	1	1	0	1	1
Rhinitis Allergic
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Rhinorrhoea
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	5 / 73 (6.85%)
occurrences all number	1	0	0	2	5
Sinus Congestion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	2 / 74 (2.70%)	2 / 73 (2.74%)
occurrences all number	0	0	1	2	2
Sleep Apnoea Syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	2
Tachypnoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Upper Respiratory Tract Inflammation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Upper-airway Cough Syndrome
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	3 / 73 (4.11%)
occurrences all number	0	1	0	1	3
Wheezing
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	1	0	0	2	0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	1	0	1	2
Anxiety
subjects affected / exposed	1 / 3 (33.33%)	2 / 15 (13.33%)	0 / 5 (0.00%)	5 / 74 (6.76%)	2 / 73 (2.74%)
occurrences all number	1	2	0	6	2
Confusional State
subjects affected / exposed	1 / 3 (33.33%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	4 / 73 (5.48%)
occurrences all number	1	1	0	1	5
Delirium
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	1	0	1	2
Depression
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	1	0	1	0
Insomnia
subjects affected / exposed	1 / 3 (33.33%)	3 / 15 (20.00%)	1 / 5 (20.00%)	6 / 74 (8.11%)	5 / 73 (6.85%)
occurrences all number	1	3	1	7	5
Mental Status Changes
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Investigations
Activated Partial Thromboplastin Time Prolonged
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	2
Alanine Aminotransferase Increased
subjects affected / exposed	1 / 3 (33.33%)	1 / 15 (6.67%)	0 / 5 (0.00%)	4 / 74 (5.41%)	4 / 73 (5.48%)
occurrences all number	1	1	0	4	7
Aspartate Aminotransferase Increased
subjects affected / exposed	1 / 3 (33.33%)	3 / 15 (20.00%)	0 / 5 (0.00%)	7 / 74 (9.46%)	5 / 73 (6.85%)
occurrences all number	1	7	0	9	7
Blood Alkaline Phosphatase Increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	2 / 74 (2.70%)	7 / 73 (9.59%)
occurrences all number	0	1	0	2	7
Blood Amylase Increased
subjects affected / exposed	1 / 3 (33.33%)	1 / 15 (6.67%)	0 / 5 (0.00%)	7 / 74 (9.46%)	2 / 73 (2.74%)
occurrences all number	2	1	0	15	7
Blood Bilirubin Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Blood Creatinine Increased
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	9 / 74 (12.16%)	5 / 73 (6.85%)
occurrences all number	1	0	0	14	9
Blood Pressure Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	0	0	0	4	5
Blood Thyroid Stimulating Hormone Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Blood Thyroid Stimulating Hormone Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	4 / 74 (5.41%)	5 / 73 (6.85%)
occurrences all number	0	0	0	6	8
Blood Urea Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0
Cardiac Murmur
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Electrocardiogram QT Prolonged
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	3 / 73 (4.11%)
occurrences all number	0	0	0	0	3
Epidermal Growth Factor Receptor Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Gamma-Glutamyltransferase Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	7
Glucose Urine Present
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Haemoglobin Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
International Normalised Ratio Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Iron Binding Capacity Total Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Lipase Increased
subjects affected / exposed	1 / 3 (33.33%)	1 / 15 (6.67%)	0 / 5 (0.00%)	5 / 74 (6.76%)	2 / 73 (2.74%)
occurrences all number	2	2	0	5	3
Liver Function Test Abnormal
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0
Liver Function Test Increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	1	0	1	0
Lymphocyte Count Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Mycobacterium Tuberculosis Complex Test Positive
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Red Blood Cells Urine
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Transaminases Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	3	0
Vitamin D Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Weight Decreased
subjects affected / exposed	0 / 3 (0.00%)	3 / 15 (20.00%)	2 / 5 (40.00%)	17 / 74 (22.97%)	27 / 73 (36.99%)
occurrences all number	0	4	7	41	68
Weight Increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	1	0	1	0
White Blood Cell Count Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
White Blood Cells Urine
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Food Intolerance
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Gout
subjects affected / exposed	2 / 3 (66.67%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	5	0	0	2	1
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Fall
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	3 / 74 (4.05%)	4 / 73 (5.48%)
occurrences all number	0	0	0	4	5
Head Injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Incisional Hernia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Infusion Related Reaction
subjects affected / exposed	0 / 3 (0.00%)	3 / 15 (20.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	19 / 73 (26.03%)
occurrences all number	0	3	0	0	21
Joint Injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Laceration
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Limb Injury
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	1	0	1	0
Lower Limb Fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	2
Muscle Strain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Post Procedural Discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Procedural pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Rib Fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Road Traffic Accident
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Skin Abrasion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Sternal Fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Thermal Burn
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Wound
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Wound Complication
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Wound Dehiscence
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	2
Cardiac disorders
Acute Coronary Syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Angina Pectoris
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Arrhythmia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Bradycardia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	3 / 74 (4.05%)	0 / 73 (0.00%)
occurrences all number	0	1	0	3	0
Bundle Branch Block Right
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Cardiac Disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Cardiac Failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Cardiac Failure Acute
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Coronary Artery Disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Coronary Artery Thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Diastolic Dysfunction
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Left Ventricular Dysfunction
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Mitral Valve Incompetence
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Pericardial Effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	0	0	1	2
Sinus Bradycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	0	0	1	2
Sinus Tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	0	0	0	2	1
Supraventricular Extrasystoles
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Tachycardia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)	1 / 74 (1.35%)	5 / 73 (6.85%)
occurrences all number	0	1	1	1	6
Tricuspid Valve Incompetence
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Ventricular Extrasystoles
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	3 / 73 (4.11%)
occurrences all number	0	0	0	0	3
Wandering Pacemaker
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Palpitations
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0
Nervous system disorders
Amnesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0
Balance Disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	2
Burning Sensation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Cerebrovascular Accident
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Cognitive Disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Convulsion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Disturbance In Attention
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Dizziness
subjects affected / exposed	1 / 3 (33.33%)	3 / 15 (20.00%)	1 / 5 (20.00%)	9 / 74 (12.16%)	10 / 73 (13.70%)
occurrences all number	1	3	1	10	11
Dizziness Postural
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0
Dysaesthesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	4
Dysgeusia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	9 / 74 (12.16%)	10 / 73 (13.70%)
occurrences all number	0	0	1	9	12
Dyskinesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Encephalopathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Headache
subjects affected / exposed	3 / 3 (100.00%)	10 / 15 (66.67%)	2 / 5 (40.00%)	12 / 74 (16.22%)	47 / 73 (64.38%)
occurrences all number	4	17	2	18	88
Hyperaesthesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Hypersomnia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Hypoaesthesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Hypotonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Lethargy
subjects affected / exposed	2 / 3 (66.67%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	2	1	0	0	1
Memory Impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	3
Mental Impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Metabolic Encephalopathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Migraine
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	5 / 73 (6.85%)
occurrences all number	0	0	0	0	8
Neuropathy Peripheral
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	1	0	2	0
Paraesthesia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	3 / 74 (4.05%)	2 / 73 (2.74%)
occurrences all number	0	2	0	3	2
Paresis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Peripheral Sensory Neuropathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	0	0	0	2	2
Presyncope
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	0	0	1	2
Sciatica
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Sinus Headache
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	2
Spinal Cord Compression
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Syncope
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	3 / 73 (4.11%)
occurrences all number	0	0	0	2	3
Tremor
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	3 / 74 (4.05%)	1 / 73 (1.37%)
occurrences all number	0	1	0	3	1
Somnolence
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	2	0	0	0	0
Speech Disorder
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	1	0	0	0	0
Ageusia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	2 / 5 (40.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	2	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 3 (33.33%)	4 / 15 (26.67%)	1 / 5 (20.00%)	12 / 74 (16.22%)	16 / 73 (21.92%)
occurrences all number	1	17	4	16	69
Leukocytosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	4
Leukopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	3
Microcytic Anaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	3	2
Polycythaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	0	0	0	3	1
Thrombocytosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	3 / 73 (4.11%)
occurrences all number	0	0	0	0	4
Haemolytic Anaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0
Ear and labyrinth disorders
Cerumen Impaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	2
Ear Discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Ear Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	3 / 73 (4.11%)
occurrences all number	0	0	0	2	3
Hearing Impaired
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	2 / 73 (2.74%)
occurrences all number	0	0	0	2	2
Hypoacusis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	1	0	1	0
Tinnitus
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	3 / 73 (4.11%)
occurrences all number	1	0	0	1	3
Tympanic Membrane Perforation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Vertigo
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Ear Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	1	0	0
Eye disorders
Cataract
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0
Eye Discharge
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Eye Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Lacrimation increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	1	0	0	2
Periorbital Oedema
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	2	0	0	2
Photophobia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	0	0	1	2
Retinal Vein Occlusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Vision Blurred
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	4 / 74 (5.41%)	2 / 73 (2.74%)
occurrences all number	0	1	0	4	2
Visual Impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	2
Ocular Hyperaemia
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	1	0	0	0	0
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	1	0	1	0
Abdominal Distension
subjects affected / exposed	0 / 3 (0.00%)	3 / 15 (20.00%)	0 / 5 (0.00%)	3 / 74 (4.05%)	1 / 73 (1.37%)
occurrences all number	0	5	0	4	1
Abdominal Hernia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Abdominal Pain
subjects affected / exposed	0 / 3 (0.00%)	5 / 15 (33.33%)	1 / 5 (20.00%)	2 / 74 (2.70%)	10 / 73 (13.70%)
occurrences all number	0	7	2	16	11
Abdominal Pain Lower
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	1	0	4	2
Abdominal Pain Upper
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	5 / 74 (6.76%)	11 / 73 (15.07%)
occurrences all number	0	0	0	6	18
Abdominal Tenderness
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Anorectal Discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Ascites
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	1	0	0	1
Cheilitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	2
Colitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Constipation
subjects affected / exposed	1 / 3 (33.33%)	5 / 15 (33.33%)	2 / 5 (40.00%)	13 / 74 (17.57%)	21 / 73 (28.77%)
occurrences all number	2	7	2	16	26
Dental Caries
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	3 / 73 (4.11%)
occurrences all number	0	0	0	0	3
Diarrhoea
subjects affected / exposed	3 / 3 (100.00%)	11 / 15 (73.33%)	4 / 5 (80.00%)	46 / 74 (62.16%)	42 / 73 (57.53%)
occurrences all number	8	32	14	120	139
Diverticulum
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Dry Mouth
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	7 / 74 (9.46%)	7 / 73 (9.59%)
occurrences all number	0	1	0	7	7
Dyskinesia Oesophageal
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0
Dyspepsia
subjects affected / exposed	1 / 3 (33.33%)	1 / 15 (6.67%)	0 / 5 (0.00%)	10 / 74 (13.51%)	6 / 73 (8.22%)
occurrences all number	1	1	0	10	6
Dysphagia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	2 / 74 (2.70%)	2 / 73 (2.74%)
occurrences all number	0	1	0	4	3
Enteritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Faecal Incontinence
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	0	0	1	2
Faeces Discoloured
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Faeces Pale
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Flatulence
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	4 / 74 (5.41%)	7 / 73 (9.59%)
occurrences all number	0	0	0	4	8
Gastritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	0	0	0	2	1
Gastrointestinal Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Gastrooesophageal Reflux Disease
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	1 / 74 (1.35%)	3 / 73 (4.11%)
occurrences all number	0	3	0	2	3
Gingival Bleeding
subjects affected / exposed	2 / 3 (66.67%)	7 / 15 (46.67%)	5 / 5 (100.00%)	3 / 74 (4.05%)	25 / 73 (34.25%)
occurrences all number	3	11	5	3	30
Gingival Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	4 / 73 (5.48%)
occurrences all number	0	0	0	1	5
Glossitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Glossodynia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	1	1	0
Haematemesis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	1	0	0	2
Haematochezia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	2 / 74 (2.70%)	2 / 73 (2.74%)
occurrences all number	0	1	0	2	2
Haemorrhoidal Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Haemorrhoids
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	2 / 74 (2.70%)	4 / 73 (5.48%)
occurrences all number	0	2	0	3	4
Hiatus Hernia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Large Intestine Perforation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Melaena
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Mesenteric Vein Thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Mouth Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Mouth Ulceration
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Nausea
subjects affected / exposed	1 / 3 (33.33%)	9 / 15 (60.00%)	4 / 5 (80.00%)	27 / 74 (36.49%)	38 / 73 (52.05%)
occurrences all number	1	16	6	43	66
Oesophageal Ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Oesophagitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Oral Discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Oral Disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Oral Dysaesthesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	0	0	1	3
Oral Mucosal Erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Oral Pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	2 / 74 (2.70%)	8 / 73 (10.96%)
occurrences all number	0	1	0	3	9
Paraesthesia Oral
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Peptic Ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Periodontal Disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	1	0	1
Proctalgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Rectal Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	3 / 73 (4.11%)
occurrences all number	0	0	0	1	3
Retching
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Salivary Hypersecretion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Stomatitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	3 / 5 (60.00%)	8 / 74 (10.81%)	18 / 73 (24.66%)
occurrences all number	0	5	6	11	34
Swollen Tongue
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Toothache
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	3 / 74 (4.05%)	0 / 73 (0.00%)
occurrences all number	0	0	0	3	0
Vomiting
subjects affected / exposed	1 / 3 (33.33%)	5 / 15 (33.33%)	4 / 5 (80.00%)	14 / 74 (18.92%)	30 / 73 (41.10%)
occurrences all number	1	8	6	23	57
Duodenitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0
Impaired Gastric Emptying
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	4	0	0	0
Periodontitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0
Hepatobiliary disorders
Bile Duct Stenosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Cholelithiasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Gallbladder Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Hepatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Liver Disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Actinic Keratosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Alopecia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	0	0	0	2	1
Blister
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Decubitus Ulcer
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	1	0	0	2
Dermatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	1	0	1
Dermatitis Acneiform
subjects affected / exposed	0 / 3 (0.00%)	3 / 15 (20.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	4 / 73 (5.48%)
occurrences all number	0	4	0	2	5
Dermatitis Bullous
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	3 / 73 (4.11%)
occurrences all number	0	0	0	0	6
Dry Skin
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	3 / 74 (4.05%)	4 / 73 (5.48%)
occurrences all number	0	0	0	3	4
Erythema
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	0 / 74 (0.00%)	6 / 73 (8.22%)
occurrences all number	0	3	0	0	6
Hyperhidrosis
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	1	0	0	2	1
Hyperkeratosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	3 / 74 (4.05%)	1 / 73 (1.37%)
occurrences all number	0	0	0	3	1
Ingrowing Nail
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	3	0
Livedo Reticularis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Nail Discolouration
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Night Sweats
subjects affected / exposed	2 / 3 (66.67%)	3 / 15 (20.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	2	3	0	0	2
Palmar-plantar Erythrodysaesthesia Syndrome
subjects affected / exposed	1 / 3 (33.33%)	5 / 15 (33.33%)	2 / 5 (40.00%)	15 / 74 (20.27%)	18 / 73 (24.66%)
occurrences all number	2	10	4	61	46
Palmoplantar Keratoderma
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Photosensitivity Reaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Pruritus
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	3 / 73 (4.11%)
occurrences all number	0	0	0	2	6
Purpura
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Rash
subjects affected / exposed	1 / 3 (33.33%)	3 / 15 (20.00%)	1 / 5 (20.00%)	6 / 74 (8.11%)	12 / 73 (16.44%)
occurrences all number	1	4	1	14	15
Rash Erythematous
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Rash Macular
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Rash Maculo-papular
subjects affected / exposed	1 / 3 (33.33%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	6 / 73 (8.22%)
occurrences all number	1	1	0	1	5
Rash Pruritic
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Rosacea
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Scab
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Skin Discolouration
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Skin Erosion
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Skin Exfoliation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	3 / 74 (4.05%)	0 / 73 (0.00%)
occurrences all number	0	0	0	4	0
Skin Hyperpigmentation
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Skin Lesion
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	1	0	1	1
Skin Ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Subcutaneous Nodule
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Swelling Face
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Telangiectasia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	5 / 73 (6.85%)
occurrences all number	0	0	0	0	5
Petechiae
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0
Renal and urinary disorders
Acute Kidney Injury
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	1	0	0	2	2
Bladder Spasm
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Dysuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Glycosuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	3	0
Haematuria
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	2 / 74 (2.70%)	8 / 73 (10.96%)
occurrences all number	0	1	0	2	8
Hydronephrosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Micturition Urgency
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	2
Nephrolithiasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Pollakiuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	0	0	0	2	1
Proteinuria
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	15 / 74 (20.27%)	3 / 73 (4.11%)
occurrences all number	0	3	0	29	4
Renal Failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	3
Urethral Meatus Stenosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Urinary Incontinence
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	2 / 73 (2.74%)
occurrences all number	0	0	0	2	2
Urinary Retention
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	0	0	1	2
Urinary Tract Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Incontinence
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0
Endocrine disorders
Adrenal Insufficiency
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Hypercalcaemia of malignancy
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Hyperthyroidism
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Hypothyroidism
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	20 / 74 (27.03%)	17 / 73 (23.29%)
occurrences all number	0	0	1	25	18
Thyroid Disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	10 / 74 (13.51%)	8 / 73 (10.96%)
occurrences all number	0	3	0	18	15
Back Pain
subjects affected / exposed	0 / 3 (0.00%)	3 / 15 (20.00%)	1 / 5 (20.00%)	17 / 74 (22.97%)	7 / 73 (9.59%)
occurrences all number	0	3	2	19	10
Bone Pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	3 / 73 (4.11%)
occurrences all number	0	1	0	0	3
Flank Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	5 / 73 (6.85%)
occurrences all number	0	0	0	3	6
Groin Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	1 / 73 (1.37%)
occurrences all number	0	0	0	2	1
Inguinal Mass
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Joint Swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Muscle Spasms
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	3 / 74 (4.05%)	2 / 73 (2.74%)
occurrences all number	0	2	0	3	2
Muscular Weakness
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	4 / 74 (5.41%)	4 / 73 (5.48%)
occurrences all number	0	1	0	6	6
Musculoskeletal Chest Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	5 / 74 (6.76%)	3 / 73 (4.11%)
occurrences all number	0	0	0	6	4
Musculoskeletal Pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	6 / 74 (8.11%)	5 / 73 (6.85%)
occurrences all number	0	2	0	6	6
Myalgia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	5 / 74 (6.76%)	7 / 73 (9.59%)
occurrences all number	0	1	0	5	9
Neck Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	4 / 74 (5.41%)	2 / 73 (2.74%)
occurrences all number	0	0	0	4	5
Osteoarthritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	5	0
Osteoporosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Pain In Extremity
subjects affected / exposed	0 / 3 (0.00%)	5 / 15 (33.33%)	0 / 5 (0.00%)	6 / 74 (8.11%)	14 / 73 (19.18%)
occurrences all number	0	6	0	10	18
Pain In Jaw
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	2	0	0	2
Pathological Fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Plantar Fasciitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Spondylolisthesis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Tendonitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Musculoskeletal Stiffness
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	2	0	0	0
Infections and infestations
Anal Abscess
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	1	0	0	1
Bronchitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Candidiasis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	1	1	0	1
Cellulitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	1	0	1	1
Cystitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	3 / 73 (4.11%)
occurrences all number	0	0	0	1	3
Dacryocanaliculitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Diarrhoea Infectious
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Folliculitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	2
Fungal Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Fungal Skin Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	0	0	2	2
Furuncle
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	2	0	0	2
Gingival Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Incision Site Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Influenza
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Kidney Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Lung Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Lymph Gland Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Nail Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Nasopharyngitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	4 / 74 (5.41%)	3 / 73 (4.11%)
occurrences all number	0	0	0	4	3
Oral Candidiasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Oral Herpes
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	4 / 73 (5.48%)
occurrences all number	0	1	0	0	6
Otitis Externa
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Otitis Media
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Paronychia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0
Pharyngitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Platelet Count Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Pneumonia
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	1 / 74 (1.35%)	3 / 73 (4.11%)
occurrences all number	0	2	0	1	3
Sepsis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Sinusitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	6 / 74 (8.11%)	3 / 73 (4.11%)
occurrences all number	0	0	2	7	5
Skin Infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	2	0	1	1
Staphylococcal Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Tinea Cruris
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0
Tinea Pedis
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	3	0
Tinea Versicolour
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Tooth Abscess
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	3 / 73 (4.11%)
occurrences all number	1	0	0	0	4
Tooth Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	4 / 74 (5.41%)	1 / 73 (1.37%)
occurrences all number	0	0	0	4	1
Upper Respiratory Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	1 / 5 (20.00%)	8 / 74 (10.81%)	6 / 73 (8.22%)
occurrences all number	0	0	1	9	9
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Urinary Tract Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	3 / 5 (60.00%)	4 / 74 (5.41%)	5 / 73 (6.85%)
occurrences all number	0	0	4	5	5
Vaginal Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	0	0	1	1
Viral Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Vulvovaginal Mycotic Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Wound Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Nasal Vestibulitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0
Pneumonial Staphylococcal
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0
Metabolism and nutrition disorders
Cachexia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	0	0	1	2
Decreased Appetite
subjects affected / exposed	3 / 3 (100.00%)	5 / 15 (33.33%)	3 / 5 (60.00%)	26 / 74 (35.14%)	21 / 73 (28.77%)
occurrences all number	3	10	4	34	40
Dehydration
subjects affected / exposed	3 / 3 (100.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	7 / 74 (9.46%)	11 / 73 (15.07%)
occurrences all number	5	3	0	15	19
Glucose Tolerance Impaired
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Hypercalcaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	5 / 74 (6.76%)	2 / 73 (2.74%)
occurrences all number	0	1	0	13	2
Hypercholesterolaemia
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	2	0	1	0
Hyperglycaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	6 / 74 (8.11%)	5 / 73 (6.85%)
occurrences all number	0	2	0	14	14
Hyperkalaemia
subjects affected / exposed	0 / 3 (0.00%)	2 / 15 (13.33%)	0 / 5 (0.00%)	1 / 74 (1.35%)	2 / 73 (2.74%)
occurrences all number	0	4	0	2	1
Hypernatraemia
subjects affected / exposed	0 / 3 (0.00%)	3 / 15 (20.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	6	0	0	1
Hyperuricaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0
Hypoalbuminaemia
subjects affected / exposed	1 / 3 (33.33%)	0 / 15 (0.00%)	0 / 5 (0.00%)	3 / 74 (4.05%)	5 / 73 (6.85%)
occurrences all number	1	0	0	5	7
Hypocalcaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	2 / 74 (2.70%)	2 / 73 (2.74%)
occurrences all number	0	5	0	2	2
Hypoglycaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	1 / 74 (1.35%)	1 / 73 (1.37%)
occurrences all number	0	2	0	1	2
Hypokalaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	4 / 74 (5.41%)	3 / 73 (4.11%)
occurrences all number	0	3	0	8	4
Hypomagnesaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)	2 / 74 (2.70%)	2 / 73 (2.74%)
occurrences all number	0	2	1	2	2
Hyponatraemia
subjects affected / exposed	1 / 3 (33.33%)	2 / 15 (13.33%)	1 / 5 (20.00%)	5 / 74 (6.76%)	12 / 73 (16.44%)
occurrences all number	1	2	1	5	17
Hypophosphataemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	1 / 5 (20.00%)	6 / 74 (8.11%)	3 / 73 (4.11%)
occurrences all number	0	1	2	7	3
Hypoproteinaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	0 / 74 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1
Hypovolaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	2 / 74 (2.70%)	0 / 73 (0.00%)
occurrences all number	0	0	0	3	0
Type 2 Diabetes Mellitus
subjects affected / exposed	0 / 3 (0.00%)	0 / 15 (0.00%)	0 / 5 (0.00%)	1 / 74 (1.35%)	0 / 73 (0.00%)
occurrences all number	0	0	0	1	0
Hyperphosphataemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 15 (6.67%)	0 / 5 (0.00%)	0 / 74 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0

More information

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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.

The study was terminated early due to lack of efficacy therefore protein biomarkers (P1b and P2), PK (P2) and disease control rate at 16 weeks by RECIST 1.1 and Choi criteria were not analyzed.

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Clinical trials

Clinical Trial Results:
A RANDOMIZED PHASE 2 TRIAL OF AXITINIB AND TRC105 VERSUS AXITINIB ALONE (INCLUDING A LEAD-IN PHASE 1B DOSE-ESCALATION PORTION) IN PATIENTS WITH ADVANCED OR METASTATIC RENAL CELL CARCINOMA

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase 1b: Number of Patients with DLT

Primary: Phase 1b: Number of Patients with DLT

Primary: Phase 2: Progression free survival (PFS) of patients with RCC

Primary: Phase 2: Progression free survival (PFS) of patients with RCC

Secondary: Phase 1b & 2: Response Rate of patients with RCC

Secondary: Phase 1b & 2: Response Rate of patients with RCC

Secondary: Phase 2: Overall Response Rate of patients with RCC by Choi

Secondary: Phase 2: Overall Response Rate of patients with RCC by Choi

Secondary: Phase 1b & 2: Trough concentrations of TRC105 by Dose Level in Phase 1b

Secondary: Phase 1b & 2: Trough concentrations of TRC105 by Dose Level in Phase 1b

Secondary: Phase 1b & 2: Number of patients with development of immunogenicity antibodies.

Secondary: Phase 1b & 2: Number of patients with development of immunogenicity antibodies.

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A RANDOMIZED PHASE 2 TRIAL OF AXITINIB AND TRC105 VERSUS AXITINIB ALONE (INCLUDING A LEAD-IN PHASE 1B DOSE-ESCALATION PORTION) IN PATIENTS WITH ADVANCED OR METASTATIC RENAL CELL CARCINOMA

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase 1b: Number of Patients with DLT

Primary: Phase 1b: Number of Patients with DLT

Primary: Phase 2: Progression free survival (PFS) of patients with RCC

Primary: Phase 2: Progression free survival (PFS) of patients with RCC

Secondary: Phase 1b & 2: Response Rate of patients with RCC

Secondary: Phase 1b & 2: Response Rate of patients with RCC

Secondary: Phase 2: Overall Response Rate of patients with RCC by Choi

Secondary: Phase 2: Overall Response Rate of patients with RCC by Choi

Secondary: Phase 1b & 2: Trough concentrations of TRC105 by Dose Level in Phase 1b

Secondary: Phase 1b & 2: Trough concentrations of TRC105 by Dose Level in Phase 1b

Secondary: Phase 1b & 2: Number of patients with development of immunogenicity antibodies.

Secondary: Phase 1b & 2: Number of patients with development of immunogenicity antibodies.

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A RANDOMIZED PHASE 2 TRIAL OF AXITINIB AND TRC105 VERSUS AXITINIB ALONE (INCLUDING A LEAD-IN PHASE 1B DOSE-ESCALATION PORTION) IN PATIENTS WITH ADVANCED OR METASTATIC RENAL CELL CARCINOMA