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    Clinical Trial Results:
    An Open-label, Randomized, Controlled, Multicenter, Phase I/II Trial Investigating 2 EMD 525797 Doses in Combination With Cetuximab and Irinotecan Versus Cetuximab and Irinotecan Alone, as Second-line Treatment for Subjects With K-ras Wild Type (WT) Metastatic Colorectal Cancer (mCRC)

    Summary
    EudraCT number
    		 2009-012040-16
    Trial protocol
    		 DE   BE   CZ   GB   HU   GR   BG  
    Global end of trial date
    28 Apr 2015

    Results information
    Results version number
    		 v2(current)
    This version publication date
    25 Jun 2016
    First version publication date
    08 May 2016
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Correction of full data set

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    EMR62242-004
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01008475
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Serono, a division of Merck KGaA
    Sponsor organisation address
    Frankfurter Strasse 250, Darmstadt, Germany, 64293
    Public contact
    Merck KGaA, Merck Serono, a division of Merck KGaA, Communication Centre Merck KGaA, 49 6151725200, service@merckgroup.com
    Scientific contact
    Merck KGaA, Merck Serono, a division of Merck KGaA, Communication Centre Merck KGaA, 49 6151725200, service@merckgroup.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    20 Apr 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Apr 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Apr 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    - To characterize the safety and tolerability profile of repeated administration of different EMD 525797 (abituzumab) dose levels in combination with cetuximab and irinotecan in subjects with k-ras WT mCRC after failure of first-line therapy with an oxaliplatin-containing regimen. - To assess the anticancer activity of 2 abituzumab doses in terms of progression-free survival time in subjects with k-ras WT mCRC after failure of first-line therapy with an oxaliplatin-containing regimen.
    Protection of trial subjects
    Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Oct 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 25
    Country: Number of subjects enrolled
    Czech Republic: 61
    Country: Number of subjects enrolled
    United Kingdom: 20
    Country: Number of subjects enrolled
    Spain: 39
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Cyprus: 1
    Country: Number of subjects enrolled
    Bulgaria: 5
    Country: Number of subjects enrolled
    Hungary: 19
    Country: Number of subjects enrolled
    Poland: 7
    Country: Number of subjects enrolled
    Russian Federation: 49
    Worldwide total number of subjects
    232
    EEA total number of subjects
    181
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    155
    From 65 to 84 years
    77
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This study consists of two parts, safety part and randomized part. A total of 16 subjects were included in the safety part and 216 subjects were included in the randomized part of the study. The subjects who participated in the safety part of the study were not included in the randomized part of the study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Safety part: EMD 525797 250 mg + SoC
    Arm description
    		 Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as intravenous (IV) infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 250 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cetuximab 400 mg/m^2 was administered on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly.

    Investigational medicinal product name
    Abituzumab
    Investigational medicinal product code
    EMD 525797
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    EMD 525797 250 mg was administered as a 1 ­hour IV infusion for every 2 weeks.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Irinotecan 180 mg/m^2 was administered as a IV infusion for 30-90 minutes for every 2 weeks.

    Arm title
    		 Safety part: EMD 525797 500 mg + SoC
    Arm description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 500 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cetuximab 400 mg/m^2 was administered on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly.

    Investigational medicinal product name
    Abituzumab
    Investigational medicinal product code
    EMD 525797
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    EMD 525797 500 mg was administered as a 1 ­hour IV infusion for every 2 weeks.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Irinotecan 180 mg/m^2 was administered as a IV infusion for 30-90 minutes for every 2 weeks.

    Arm title
    		 Safety part: EMD525797 750 mg + SoC
    Arm description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 750 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cetuximab 400 mg/m^2 was administered on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly.

    Investigational medicinal product name
    Abituzumab
    Investigational medicinal product code
    EMD 525797
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    EMD 525797 750 mg was administered as a 1 ­hour IV infusion for every 2 weeks.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Irinotecan 180 mg/m^2 was administered as a IV infusion for 30-90 minutes for every 2 weeks.

    Arm title
    		 Safety part: EMD 525797 1000 mg +SoC
    Arm description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cetuximab 400 mg/m^2 was administered on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly.

    Investigational medicinal product name
    Abituzumab
    Investigational medicinal product code
    EMD 525797
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    EMD 525797 1000 mg was administered as a 1 ­hour IV infusion for every 2 weeks.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Irinotecan 180 mg/m^2 was administered as a IV infusion for 30-90 minutes for every 2 weeks.

    Arm title
    		 Randomized Part: Standard of Care (SoC)
    Arm description
    		 Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as intravenous (IV) infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly followed by irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.
    Arm type
    		 Control

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cetuximab 400 mg/m^2 was administered on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Irinotecan 180 mg/m^2 was administered as a IV infusion for 30-90 minutes for every 2 weeks.

    Arm title
    		 Randomized part: EMD 525797 500 mg + SoC
    Arm description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 500 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cetuximab 400 mg/m^2 was administered on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly.

    Investigational medicinal product name
    Abituzumab
    Investigational medicinal product code
    EMD 525797
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    EMD 525797 500 mg was administered as a 1 ­hour IV infusion for every 2 weeks.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Irinotecan 180 mg/m^2 was administered as a IV infusion for 30-90 minutes for every 2 weeks.

    Arm title
    		 Randomized Part: EMD 525797 1000 mg + SoC
    Arm description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cetuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cetuximab 400 mg/m^2 was administered on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Irinotecan 180 mg/m^2 was administered as a IV infusion for 30-90 minutes for every 2 weeks.

    Investigational medicinal product name
    Abituzumab
    Investigational medicinal product code
    EMD 525797
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    EMD 525797 1000 mg was administered as a 1 ­hour IV infusion for every 2 weeks.

    Number of subjects in period 1
    		Safety part: EMD 525797 250 mg + SoC Safety part: EMD 525797 500 mg + SoC Safety part: EMD525797 750 mg + SoC Safety part: EMD 525797 1000 mg +SoC Randomized Part: Standard of Care (SoC) Randomized part: EMD 525797 500 mg + SoC Randomized Part: EMD 525797 1000 mg + SoC
    Started
    3
    3
    7
    3
    72
    73
    71
    Completed
    3
    3
    7
    3
    67
    67
    67
    Not completed
    0
    0
    0
    0
    5
    6
    4
         Ongoing treatment at data cut-off date
    -
    -
    -
    -
    5
    5
    4
         Subject randomized to 1000 mg group received SoC
    -
    -
    -
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Safety part: EMD 525797 250 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as intravenous (IV) infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 250 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Safety part: EMD 525797 500 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 500 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Safety part: EMD525797 750 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 750 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Safety part: EMD 525797 1000 mg +SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Randomized Part: Standard of Care (SoC)
    Reporting group description
    		 Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as intravenous (IV) infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly followed by irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Randomized part: EMD 525797 500 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 500 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Randomized Part: EMD 525797 1000 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group values
    		 Safety part: EMD 525797 250 mg + SoC Safety part: EMD 525797 500 mg + SoC Safety part: EMD525797 750 mg + SoC Safety part: EMD 525797 1000 mg +SoC Randomized Part: Standard of Care (SoC) Randomized part: EMD 525797 500 mg + SoC Randomized Part: EMD 525797 1000 mg + SoC Total
    Number of subjects
    		 3 3 7 3 72 73 71 232
    Age categorical
    Units: Subjects
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 62.3 ± 11.5 57.7 ± 11.2 60.4 ± 6.2 63 ± 7.2 56.2 ± 12.11 58.9 ± 12.18 59.9 ± 10.63 -
    Gender, Male/Female
    Units: Subjects
        Female
    		 2 1 4 2 27 36 23 95
        Male
    		 1 2 3 1 45 37 48 137

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Safety part: EMD 525797 250 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as intravenous (IV) infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 250 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Safety part: EMD 525797 500 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 500 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Safety part: EMD525797 750 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 750 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Safety part: EMD 525797 1000 mg +SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Randomized Part: Standard of Care (SoC)
    Reporting group description
    		 Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as intravenous (IV) infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly followed by irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Randomized part: EMD 525797 500 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 500 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Randomized Part: EMD 525797 1000 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    Safety part: EMD 525797 250 mg + Standard of Care (SoC)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 once weekly followed by EMD 525797 at a target dose of 250 mg as a 1-hour IV infusion for every 2 weeks, followed by irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    Safety part: EMD 525797 750 mg + SoC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 once weekly followed by EMD 525797 at a target dose of 750 mg as a 1-hour IV infusion for every 2 weeks, followed by irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    Safety part: EMD 525797 1000 mg + SoC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 once weekly followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    Randomized part: SoC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as intravenous (IV) infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly followed by irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    Randomized part: EMD 525797 1000 mg + SoC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    Safety Part: EMD 525797 250 mg + SoC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 250 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    Safety Part: EMD 525797 500 mg + SoC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 500 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    Safety Part: EMD525797 750 mg + SoC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 750 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    Safety Part: EMD 525797 1000 mg +SoC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    Standard of Care (SoC)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as intravenous (IV) infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly followed by irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radiographically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    EMD 525797 500 mg + SoC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 500 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radiographically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Subject analysis set title
    EMD 525797 1000 mg + SoC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Primary: Safety Part: Number of subjects experiencing DLTs (dose limiting toxicity)

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    End point title
    		 Safety Part: Number of subjects experiencing DLTs (dose limiting toxicity) [1]
    End point description
    DLT :any Grade 4 hematologic toxicity/ Grade 3/4 non-hematologic toxicity assessed as related to trial treatment by Investigator &/or Sponsor & confirmed by safety monitoring committee (SMC) to be relevant to combination treatment within 1 cycle of therapy. Any Grade 3/ 4 non haematological toxicity,any Grade 4 hematological toxicity,treatment related deaths within first 2 weeks of therapy.Toxicities excluded from DLT: alopecia,rash,nausea,vomiting & hypomagnesemia of Grade 3/ 4 severity,Grade 4 neutropenia/ leukopenia lasting for =< 5 days & not associated with fever; Single lab values out of normal range without any clinical correlation & resolve within 7 days; Grade 3 or 4 diarrhoea without adequate supportive care. Adequate supportive care has been administered & Grade 4 diarrhoea persists (investigator decision); isolated Grade 4 lymphocytopenia and thrombocytopenia without clinical correlation. Dose-escalation analysis set was used for the evaluation of the endpoint.
    End point type
    Primary
    End point timeframe
    Time from the first dose of study drug up to 2 weeks
    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: Only descriptive summary statistics was planned for this outcome measure.
    End point values
    		 Safety Part: EMD 525797 250 mg + SoC Safety Part: EMD 525797 500 mg + SoC Safety Part: EMD525797 750 mg + SoC Safety Part: EMD 525797 1000 mg +SoC
    Number of subjects analysed
    3
    3
    7
    3
    Units: subjects
        number (not applicable)
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Randomized Part: Progression free survival (PFS)

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    End point title
    		 Randomized Part: Progression free survival (PFS)
    End point description
    PFS:the time from the randomization date to first documented sign of objective radio-graphic disease progression (PD) as per Response Evaluation Criteria In Solid Tumors version 1. (RECIST 1.0) or death from any cause if reported within 12 weeks from last tumor assessment. PD per RECIST v 1.0 was defined as at least 20% increase in sum of longest diameter of target lesions, taking as the reference smallest sum of longest diameters recorded since treatment started, or unequivocal progression of existing non-target lesion or appearance of new lesions. Subjects who did not progress or died at the time of analyses, or subjects who died without previously radio-graphically documented PD and death was observed after more than 12 weeks of last tumor assessment without progression, these subjects were censored at their last tumor assessment date or date of randomization, whichever occurred last. Intention-to-treat (ITT) analysis set: all the subjects who were randomized into treatment groups.
    End point type
    Primary
    End point timeframe
    Time from randomization until progressive disease or death; assessed up to 18 months (i.e data cut-off date: 09 Oct 2013)
    End point values
    		 Standard of Care (SoC) EMD 525797 500 mg + SoC EMD 525797 1000 mg + SoC
    Number of subjects analysed
    72
    73
    71
    Units: months
        median (confidence interval 95%)
    5.6 (4.2 to 6.9)
    5.4 (4.1 to 6)
    5.6 (4.1 to 6.9)
    Statistical analysis title
    		 SoC vs EMD 525797 500 mg + SoC
    Comparison groups
    Standard of Care (SoC) v EMD 525797 500 mg + SoC
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.64
    Statistical analysis title
    		 SoC vs EMD 525797 1000 mg + SoC
    Comparison groups
    Standard of Care (SoC) v EMD 525797 1000 mg + SoC
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.61

    Secondary: Overall survival (OS) time

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    End point title
    		 Overall survival (OS) time
    End point description
    OS was defined as the time from the date of randomization to the date of death from any cause. For subjects who were still alive at the analysis cut off date or lost to follow up, survival was censored at the last recorded date the subject was known to be alive or at the analysis cut off date, whichever occurred first. ITT analysis set included all the subjects who were randomized into the trial.
    End point type
    Secondary
    End point timeframe
    Time from randomization until death assessed up to 18 months (i.e data cut-off date: 09 Oct 2013)
    End point values
    		 Standard of Care (SoC) EMD 525797 500 mg + SoC EMD 525797 1000 mg + SoC
    Number of subjects analysed
    72
    73
    71
    Units: months
        median (confidence interval 95%)
    11.6 (9.8 to 15.7)
    15 (10.9 to 19.2)
    14.4 (9.8 to 19.3)
    Statistical analysis title
    		 SoC vs EMD 525797 500 mg + SoC
    Comparison groups
    Standard of Care (SoC) v EMD 525797 500 mg + SoC
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.28
    Statistical analysis title
    		 SoC vs EMD 525797 1000 mg + SoC
    Comparison groups
    Standard of Care (SoC) v EMD 525797 1000 mg + SoC
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 1.25

    Secondary: Time to progression (TTP)

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    End point title
    		 Time to progression (TTP)
    End point description
    TTP was defined as the time from the date of randomization to the date of objective radiographic disease progression (PD). PD per RECIST v 1.0 was defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as the reference the smallest sum of longest diameters recorded since treatment started, or unequivocal progression of existing non-target lesion or appearance of new lesions. For subjects who did not progress or who were without any post baseline tumor assessment, TTP was censored at their last tumor assessment date, or at the randomization date, whichever occurred last. ITT analysis set included all the subjects who were randomized into the trial.
    End point type
    Secondary
    End point timeframe
    Time from randomization until disease progression assessed up to 18 months (i.e data cut-off date: 09 Oct 2013)
    End point values
    		 Standard of Care (SoC) EMD 525797 500 mg + SoC EMD 525797 1000 mg + SoC
    Number of subjects analysed
    72
    73
    71
    Units: months
        median (confidence interval 95%)
    5.8 (4.4 to 7.2)
    5.6 (4.2 to 8.3)
    6.5 (4.2 to 7.1)
    Statistical analysis title
    		 SoC vs EMD 525797 500 mg + SoC
    Comparison groups
    Standard of Care (SoC) v EMD 525797 500 mg + SoC
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.65
    Statistical analysis title
    		 SoC vs EMD 525797 1000 mg + SoC
    Comparison groups
    Standard of Care (SoC) v EMD 525797 1000 mg + SoC
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.65

    Secondary: Number of subjects with Tumor response

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    End point title
    		 Number of subjects with Tumor response
    End point description
    Tumor response was defined as the presence of at least 1 confirmed complete response (CR) or confirmed partial response (PR) as judged by RECIST version 1.0. CR was defined for target lesions (TLs) as the disappearance of all lesions, and for non-target lesions (NTLs) as the disappearance of all non-target non-measurable lesions and/or normalization of serum levels of tumor markers. PR was defined for TLs as at least a 30 percent (%) decrease from baseline (BL) in the sum of longest diameter (SLD) of TLs. ITT analysis set included all the subjects who were randomized into the trial.
    End point type
    Secondary
    End point timeframe
    Time from randomization up to 18 months (i.e data cut-off date: 09 Oct 2013)
    End point values
    		 Standard of Care (SoC) EMD 525797 500 mg + SoC EMD 525797 1000 mg + SoC
    Number of subjects analysed
    72
    73
    71
    Units: Subjects
    number (not applicable)
        CR
    2
    1
    0
        PR
    17
    19
    18
    No statistical analyses for this end point

    Secondary: Time to treatment failure (TTF)

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    End point title
    		 Time to treatment failure (TTF)
    End point description
    TTF was defined as the time from randomization to treatment discontinuation for any reason. For subjects on drug at the analysis cut off date or lost to follow up, TTF was censored at the trial discontinuation date or at the analysis cut off date, whichever occurred first. ITT analysis set included all the subjects who were randomized into the trial.
    End point type
    Secondary
    End point timeframe
    Time from randomization until discontinuation assessed up to 18 months (i.e data cut-off date: 09 Oct 2013)
    End point values
    		 Standard of Care (SoC) EMD 525797 500 mg + SoC EMD 525797 1000 mg + SoC
    Number of subjects analysed
    72
    73
    71
    Units: months
        median (confidence interval 95%)
    5.2 (4.4 to 6.2)
    4.3 (3.6 to 6.1)
    4.8 (3.3 to 6.6)
    Statistical analysis title
    		 SoC vs EMD 525797 500 mg + SoC
    Comparison groups
    Standard of Care (SoC) v EMD 525797 500 mg + SoC
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.34
    Statistical analysis title
    		 SoC vs EMD 525797 1000 mg + SoC
    Comparison groups
    Standard of Care (SoC) v EMD 525797 1000 mg + SoC
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.48

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first dose of study drug administration up to 50 days after the last dose of study drug administration
    Adverse event reporting additional description
    The safety analysis set included all subjects who received at least 1 dose of the trial medication. 1 subject who was randomized to EMD525797 1000 mg group received only SoC, therefore this subjects was reported under the SOC group.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Safety Part: EMD 525797 250 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 250 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Safety Part: EMD 525797 500 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 500 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Safety Part: EMD525797 750 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 750 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Safety Part: EMD 525797 1000 mg +SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    Standard of Care (SoC)
    Reporting group description
    		 Cetuximab was administered at a dose of 400 milligram per square meter (mg/m^2) on Day 1 Cycle 1 (Week 1) as intravenous (IV) infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly followed by irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radiographically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    EMD 525797 500 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 500 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radiographically documented PD (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Reporting group title
    EMD 525797 1000 mg + SoC
    Reporting group description
    		 Cetuximab was administered at a dose of 400 mg/m^2 on Day 1 Cycle 1 (Week 1) as IV infusion for 2 hours, and then at a dose of 250 mg/m^2 on Day 8 (Week 2) once weekly; followed by EMD 525797 at a target dose of 1000 mg as a 1-hour IV infusion for every 2 weeks, followed by Irinotecan at a dose of 180 mg/m^2 as IV infusion for 30-90 minutes for every 2 weeks until radio-graphically documented progressive disease (PD) (as assessed by the investigator), unacceptable toxicity or eligibility for curative resection (investigator’s assessment), or withdrawal of consent.

    Serious adverse events
    		 Safety Part: EMD 525797 250 mg + SoC Safety Part: EMD 525797 500 mg + SoC Safety Part: EMD525797 750 mg + SoC Safety Part: EMD 525797 1000 mg +SoC Standard of Care (SoC) EMD 525797 500 mg + SoC EMD 525797 1000 mg + SoC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    3 / 7 (42.86%)
    3 / 3 (100.00%)
    30 / 73 (41.10%)
    27 / 72 (37.50%)
    34 / 69 (49.28%)
         number of deaths (all causes)
    0
    0
    2
    0
    45
    39
    35
         number of deaths resulting from adverse events
    6
    Vascular disorders
    Deep Vein Thrombosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous Thrombosis Limb
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Surgical and medical procedures
    Thrombosis Prophylaxis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Device Malfunction
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disease Progression
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    2 / 72 (2.78%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General Physical Health Deterioration
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal Inflammation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 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
    0 / 0
    0 / 0
    Multi-Organ Failure
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Performance Status Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Pyrexia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic Shock
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Hypersensitivity
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Dyspnoea Exertional
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Pulmonary Embolism
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    5 / 73 (6.85%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 5
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Respiratory Failure
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Investigations
    Blood Bilirubin Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood Creatinine Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Coagulation Factor Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Gamma-Glutamyltransferase Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    General Physical Condition Abnormal
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 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
    0 / 0
    0 / 0
    Neutrophil Count Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femoral Neck Fracture
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Overdose
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial Fibrillation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac Failure Acute
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    1 / 1
    0 / 0
    Tachyarrhythmia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    Tachycardia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular Accident
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    1 / 1
    0 / 0
    Coma
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Dizziness
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Epilepsy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Polyneuropathy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Syncope
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile Neutropenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    3 / 72 (4.17%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    1 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Hernia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    1 / 1
    0 / 0
    Abdominal Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    5 / 69 (7.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Colonic Obstruction
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Diarrhoea
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    7 / 69 (10.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Enterovesical Fistula
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Gastrointestinal Haemorrhage
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Stenosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Toxicity
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Ulcer Haemorrhage
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    1 / 1
    0 / 0
    Intestinal Obstruction
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Intestinal Perforation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periodontitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Subileus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Vomiting
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    2 / 72 (2.78%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Hepatic Failure
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Hyperbilirubinaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Jaundice Cholestatic
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Rash Maculo-Papular
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Toxic Skin Eruption
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal Failure
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal Failure Acute
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Inappropriate Antidiuretic Hormone Secretion
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Neck Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Pathological Fracture
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal Sepsis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal Wall Abscess
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Device Related Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Device Related Sepsis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Gastrointestinal Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Pneumonia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal Abscess
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Sepsis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Septic Shock
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Decreased Appetite
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes Mellitus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrolyte Imbalance
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Safety Part: EMD 525797 250 mg + SoC Safety Part: EMD 525797 500 mg + SoC Safety Part: EMD525797 750 mg + SoC Safety Part: EMD 525797 1000 mg +SoC Standard of Care (SoC) EMD 525797 500 mg + SoC EMD 525797 1000 mg + SoC
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    7 / 7 (100.00%)
    3 / 3 (100.00%)
    72 / 73 (98.63%)
    72 / 72 (100.00%)
    68 / 69 (98.55%)
    Vascular disorders
    Aortic Thrombosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Circulatory Collapse
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Deep Vein Thrombosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    3
    Flushing
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Haematoma
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    Hypertension
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    2 / 72 (2.78%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    1
    0
    3
    2
    3
    Hypotension
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    2 / 72 (2.78%)
    5 / 69 (7.25%)
         occurrences all number
    0
    0
    0
    0
    2
    3
    6
    Orthostatic Hypotension
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Pallor
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Peripheral Ischaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Phlebitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Thrombophlebitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Thrombosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Venous Insufficiency
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    Venous Thrombosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    General disorders and administration site conditions
    Asthenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    9 / 73 (12.33%)
    15 / 72 (20.83%)
    20 / 69 (28.99%)
         occurrences all number
    0
    2
    3
    1
    15
    26
    66
    Catheter Site Erythema
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    0
    Catheter Site Rash
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Chest Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Chills
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    4
    Extravasation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Fatigue
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    15 / 73 (20.55%)
    16 / 72 (22.22%)
    17 / 69 (24.64%)
         occurrences all number
    0
    0
    3
    0
    21
    26
    33
    Feeling Cold
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    General Physical Health Deterioration
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Impaired Healing
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Influenza Like Illness
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    2
    Injection Site Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Localised Oedema
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Malaise
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Mucosal Inflammation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    3 / 7 (42.86%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    3
    0
    0
    1
    1
    Non-Cardiac Chest Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    Oedema Peripheral
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    4 / 72 (5.56%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    1
    0
    4
    5
    5
    Performance Status Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Pyrexia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    4 / 73 (5.48%)
    13 / 72 (18.06%)
    8 / 69 (11.59%)
         occurrences all number
    0
    0
    0
    1
    5
    23
    19
    Secretion Discharge
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Xerosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    2
    Immune system disorders
    Contrast Media Allergy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Drug Hypersensitivity
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    1
    Hypersensitivity
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    Reproductive system and breast disorders
    Balanitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Breast Mass
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Breast Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Haematospermia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Pelvic Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Vulvovaginal Pruritus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Asthmatic Crisis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Bronchial Secretion Retention
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Cough
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    7 / 73 (9.59%)
    6 / 72 (8.33%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    1
    0
    8
    6
    3
    Dysphonia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    2
    Dyspnoea
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    2
    Dyspnoea Exertional
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    4 / 72 (5.56%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    3
    5
    1
    Epistaxis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    7 / 73 (9.59%)
    5 / 72 (6.94%)
    7 / 69 (10.14%)
         occurrences all number
    4
    0
    0
    2
    8
    6
    8
    Haemoptysis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    1
    Hiccups
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Hypoxia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Nasal Congestion
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Nasal Dryness
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Obstructive Airways Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Oropharyngeal Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    5 / 69 (7.25%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    6
    Productive Cough
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Pulmonary Embolism
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Pulmonary Toxicity
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Respiratory Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    4
    0
    Rhinitis Allergic
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Rhinorrhoea
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Sputum Discoloured
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Throat Irritation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Psychiatric disorders
    Agitation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    1
    Anxiety
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    2 / 73 (2.74%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    1
    4
    1
    0
    Confusional State
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Decreased Interest
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Depressed Mood
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    3
    Depression
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Depressive Symptom
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Emotional Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Insomnia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    2 / 72 (2.78%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    6
    Investigations
    Activated Partial Thromboplastin Time
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Activated Partial Thromboplastin Time Prolonged
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    4 / 72 (5.56%)
    0 / 69 (0.00%)
         occurrences all number
    5
    0
    0
    0
    2
    4
    0
    Alanine Aminotransferase Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    12 / 73 (16.44%)
    4 / 72 (5.56%)
    3 / 69 (4.35%)
         occurrences all number
    1
    0
    0
    1
    22
    5
    5
    Aspartate Aminotransferase Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    8 / 73 (10.96%)
    4 / 72 (5.56%)
    4 / 69 (5.80%)
         occurrences all number
    1
    0
    0
    0
    9
    4
    7
    Blood Alkaline Phosphatase Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    4 / 73 (5.48%)
    2 / 72 (2.78%)
    6 / 69 (8.70%)
         occurrences all number
    0
    0
    0
    1
    7
    3
    10
    Blood Bilirubin Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    2
    0
    0
    0
    2
    0
    4
    Blood Glucose Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    12
    Blood Iron Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Blood Lactate Dehydrogenase Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    3 / 72 (4.17%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    10
    1
    Blood Magnesium Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Blood Pressure Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    Blood Thyroid Stimulating Hormone Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Blood Thyroid Stimulating Hormone Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    0
    Body Temperature Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    2 / 3 (66.67%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    3
    1
    0
    0
    C-Reactive Protein Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Creatinine Renal Clearance Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Ejection Fraction Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Electrocardiogram T Wave Inversion
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Eosinophil Count Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Gamma-Glutamyltransferase Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    2 / 73 (2.74%)
    1 / 72 (1.39%)
    3 / 69 (4.35%)
         occurrences all number
    1
    0
    0
    1
    10
    1
    6
    Haematocrit Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Haemoglobin Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    1
    International Normalised Ratio Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    3 / 72 (4.17%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    4
    0
    Neutrophil Count Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    6
    Neutrophil Count Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Platelet Count Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Red Blood Cell Count Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Thrombin Time Prolonged
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    Transaminases Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Urine Output Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Weight Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    7 / 72 (9.72%)
    10 / 69 (14.49%)
         occurrences all number
    1
    0
    0
    0
    3
    7
    12
    Weight Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    White Blood Cell Count Increased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Contrast Media Reaction
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Fall
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    2
    Head Injury
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Incisional Hernia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Infusion Related Reaction
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    4 / 72 (5.56%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    5
    1
    Post Procedural Discharge
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Post Procedural Haemorrhage
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Procedural Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    Radius Fracture
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Sunburn
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Suture Related Complication
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Wound
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Congenital, familial and genetic disorders
    Congenital Hair Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Trichomegaly
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    Cardiac disorders
    Angina Pectoris
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Atrial Tachycardia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Left Ventricular Dysfunction
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Myocardial Ischaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Right Ventricular Dysfunction
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Sinus Tachycardia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    1
    Supraventricular Extrasystoles
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Tachycardia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Ventricular Extrasystoles
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Nervous system disorders
    Cholinergic Syndrome
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    2 / 72 (2.78%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    2
    0
    4
    3
    3
    Diabetic Neuropathy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Dizziness
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    2
    0
    0
    4
    1
    Dizziness Postural
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Dysgeusia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    8 / 69 (11.59%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    8
    Encephalopathy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Epilepsy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Headache
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    1 / 72 (1.39%)
    3 / 69 (4.35%)
         occurrences all number
    1
    0
    0
    0
    3
    2
    3
    Hepatic Encephalopathy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hypoaesthesia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Hypogeusia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Lethargy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    2 / 72 (2.78%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    0
    0
    6
    3
    4
    Neuropathy Peripheral
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Neurotoxicity
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    Paraesthesia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    2
    Peripheral Motor Neuropathy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Peripheral Sensory Neuropathy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    1
    0
    4
    0
    2
    Polyneuropathy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    1 / 73 (1.37%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    2
    1
    1
    2
    1
    Radiculitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    Sciatica
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Speech Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Toxic Neuropathy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Tremor
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Visual Field Defect
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Agranulocytosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Anaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    9 / 73 (12.33%)
    15 / 72 (20.83%)
    18 / 69 (26.09%)
         occurrences all number
    3
    0
    0
    1
    28
    40
    33
    Anaemia Of Malignant Disease
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    7
    0
    Aplastic Anaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    6
    3
    Granulocytopenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    0
    Haemorrhagic Anaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Hypochromic Anaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Iron Deficiency Anaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    5
    8
    5
    Leukocytosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    3 / 72 (4.17%)
    4 / 69 (5.80%)
         occurrences all number
    9
    0
    0
    0
    2
    3
    5
    Leukopenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 3 (33.33%)
    3 / 7 (42.86%)
    2 / 3 (66.67%)
    14 / 73 (19.18%)
    14 / 72 (19.44%)
    16 / 69 (23.19%)
         occurrences all number
    3
    1
    6
    4
    63
    55
    70
    Lymphadenitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Lymphadenopathy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Lymphopenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    Microcytic Anaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Neutropenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    2 / 3 (66.67%)
    24 / 73 (32.88%)
    26 / 72 (36.11%)
    26 / 69 (37.68%)
         occurrences all number
    3
    0
    1
    5
    96
    91
    85
    Normochromic Normocytic Anaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    Splenic Vein Thrombosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Thrombocytopenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    7 / 73 (9.59%)
    2 / 72 (2.78%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    0
    1
    17
    3
    4
    Thrombocytosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Ear and labyrinth disorders
    External Ear Inflammation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hypoacusis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Tinnitus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Vertigo
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    1
    Vertigo Positional
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Eye disorders
    Blepharitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    2
    Conjunctivitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    9 / 73 (12.33%)
    4 / 72 (5.56%)
    8 / 69 (11.59%)
         occurrences all number
    0
    0
    1
    0
    21
    6
    14
    Dry Eye
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Erythema Of Eyelid
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Eye Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Eyelid Oedema
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Eyelid Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Eyelids Pruritus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Iritis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Meibomianitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Miosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Ocular Hyperaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Ocular Icterus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Vision Blurred
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Visual Acuity Reduced
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Visual Impairment
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Gastrointestinal disorders
    Abdominal Discomfort
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Abdominal Distension
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    3
    2
    1
    Abdominal Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    11 / 73 (15.07%)
    14 / 72 (19.44%)
    18 / 69 (26.09%)
         occurrences all number
    0
    1
    1
    0
    18
    24
    24
    Abdominal Pain Lower
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Abdominal Pain Upper
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    5 / 73 (6.85%)
    5 / 72 (6.94%)
    6 / 69 (8.70%)
         occurrences all number
    0
    0
    0
    0
    8
    5
    7
    Abdominal Tenderness
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Anal Haemorrhage
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    Anorectal Discomfort
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Aphthous Stomatitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    2 / 3 (66.67%)
    2 / 73 (2.74%)
    4 / 72 (5.56%)
    9 / 69 (13.04%)
         occurrences all number
    0
    1
    0
    2
    2
    4
    16
    Ascites
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    3 / 72 (4.17%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    3
    0
    Cheilitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Colitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Constipation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    7 / 73 (9.59%)
    7 / 72 (9.72%)
    15 / 69 (21.74%)
         occurrences all number
    0
    0
    2
    1
    14
    13
    22
    Diarrhoea
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    4 / 7 (57.14%)
    2 / 3 (66.67%)
    31 / 73 (42.47%)
    48 / 72 (66.67%)
    45 / 69 (65.22%)
         occurrences all number
    2
    0
    10
    15
    128
    197
    209
    Dry Mouth
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    2
    Dyspepsia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    4 / 73 (5.48%)
    5 / 72 (6.94%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    0
    6
    6
    2
    Dysphagia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Enteritis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    0
    Enterovesical Fistula
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Faecal Vomiting
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Flatulence
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    7 / 69 (10.14%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    8
    Food Poisoning
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Frequent Bowel Movements
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gastritis Erosive
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gastrointestinal Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    3
    Gastrointestinal Motility Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gastrointestinal Toxicity
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Gastrooesophageal Reflux Disease
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    1
    Gastrooesophageal Sphincter Insufficiency
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gingival Bleeding
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    2
    Haematochezia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Haemorrhoidal Haemorrhage
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Haemorrhoids
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    3 / 72 (4.17%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    3
    3
    2
    Intestinal Fistula
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Intestinal Haemorrhage
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Intestinal Villi Atrophy
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Lip Ulceration
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Mesenteric Vein Thrombosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Mouth Ulceration
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    2
    Mucous Stools
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Nausea
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    21 / 73 (28.77%)
    25 / 72 (34.72%)
    25 / 69 (36.23%)
         occurrences all number
    5
    4
    2
    2
    41
    62
    59
    Odynophagia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Oral Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Pancreatitis Acute
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Paraesthesia Oral
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Periodontal Disease
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    2
    Proctalgia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    4 / 72 (5.56%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    0
    0
    2
    6
    3
    Rectal Discharge
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Rectal Haemorrhage
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    3 / 72 (4.17%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    0
    0
    2
    5
    2
    Rectal Tenesmus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Stomatitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    8 / 73 (10.96%)
    18 / 72 (25.00%)
    21 / 69 (30.43%)
         occurrences all number
    0
    0
    3
    0
    9
    37
    35
    Subileus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Tongue Ulceration
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Tooth Discolouration
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Tooth Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Toothache
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Vomiting
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    2 / 3 (66.67%)
    14 / 73 (19.18%)
    12 / 72 (16.67%)
    17 / 69 (24.64%)
         occurrences all number
    0
    3
    1
    6
    21
    24
    30
    Hepatobiliary disorders
    Biliary Colic
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Cholestasis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hepatic Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    Hepatic Vein Thrombosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Hepatomegaly
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Hyperbilirubinaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    4 / 72 (5.56%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    0
    0
    2
    16
    4
    Jaundice
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    1
    Skin and subcutaneous tissue disorders
    Acne
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    12 / 73 (16.44%)
    7 / 72 (9.72%)
    12 / 69 (17.39%)
         occurrences all number
    0
    0
    6
    0
    26
    18
    33
    Alopecia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    2 / 3 (66.67%)
    19 / 73 (26.03%)
    12 / 72 (16.67%)
    15 / 69 (21.74%)
         occurrences all number
    1
    0
    2
    2
    26
    19
    26
    Dermal Cyst
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Dermatitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    Dermatitis Acneiform
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    13 / 73 (17.81%)
    14 / 72 (19.44%)
    18 / 69 (26.09%)
         occurrences all number
    3
    0
    7
    5
    19
    41
    42
    Dermatitis Allergic
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Dermatitis Atopic
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    5
    0
    Drug Eruption
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    0
    0
    6
    0
    5
    Dry Skin
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    9 / 73 (12.33%)
    9 / 72 (12.50%)
    11 / 69 (15.94%)
         occurrences all number
    1
    0
    0
    0
    14
    19
    16
    Eczema
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    Erythema
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    2 / 73 (2.74%)
    5 / 72 (6.94%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    3
    1
    2
    14
    4
    Exfoliative Rash
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hyperhidrosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    2
    Hyperkeratosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Hypertrichosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    4
    Ingrowing Nail
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    2
    Intertrigo
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Nail Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    2
    0
    Nail Toxicity
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    4
    Night Sweats
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    Onychoclasis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Palmar-Plantar Erythrodysaesthesia Syndrome
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    7 / 73 (9.59%)
    7 / 72 (9.72%)
    7 / 69 (10.14%)
         occurrences all number
    0
    0
    0
    0
    10
    12
    16
    Panniculitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Penile Ulceration
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Petechiae
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Pigmentation Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Prurigo
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Pruritus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    6 / 73 (8.22%)
    9 / 72 (12.50%)
    10 / 69 (14.49%)
         occurrences all number
    1
    0
    2
    0
    8
    13
    15
    Pruritus Generalised
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Rash
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    3 / 3 (100.00%)
    1 / 7 (14.29%)
    3 / 3 (100.00%)
    37 / 73 (50.68%)
    37 / 72 (51.39%)
    28 / 69 (40.58%)
         occurrences all number
    4
    5
    3
    4
    75
    103
    76
    Rash Generalised
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Rash Maculo-Papular
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    4
    Rash Papular
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    3 / 72 (4.17%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    4
    6
    Rash Pruritic
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    6
    Rash Vesicular
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Skin Chapped
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Skin Erosion
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Skin Exfoliation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Skin Fissures
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    9 / 73 (12.33%)
    5 / 72 (6.94%)
    5 / 69 (7.25%)
         occurrences all number
    2
    0
    0
    0
    12
    14
    8
    Skin Irritation
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    Skin Ulcer
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Subcutaneous Nodule
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Toxic Skin Eruption
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    4
    5
    5
    Renal and urinary disorders
    Anuria
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Dysuria
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    4 / 72 (5.56%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    2
    5
    3
    Glycosuria
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    Haematuria
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    1
    1
    1
    1
    3
    Leukocyturia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Nephrolithiasis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Oliguria
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Polyuria
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Proteinuria
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    5
    Renal Colic
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Renal Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Urethral Obstruction
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Urinary Retention
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Endocrine disorders
    Hyperthyroidism
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Hypothyroidism
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    4 / 73 (5.48%)
    3 / 72 (4.17%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    7
    3
    2
    Back Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    5 / 73 (6.85%)
    3 / 72 (4.17%)
    9 / 69 (13.04%)
         occurrences all number
    0
    2
    0
    0
    5
    5
    10
    Flank Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Groin Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Inguinal Mass
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Joint Swelling
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Mobility Decreased
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Muscle Spasms
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    2 / 72 (2.78%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    0
    0
    2
    3
    5
    Muscle Twitching
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Muscular Weakness
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Musculoskeletal Chest Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    2
    Musculoskeletal Pain
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Myalgia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    2 / 72 (2.78%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    1
    Osteoarthritis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Osteopenia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Osteoporosis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Pain In Extremity
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    0 / 72 (0.00%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    8
    Soft Tissue Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Synovitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Infections and infestations
    Abdominal Wall Abscess
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Abscess
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Anal Abscess
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Bronchitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    4 / 72 (5.56%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    5
    0
    Catheter Site Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Cellulitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    3
    Cystitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    3 / 72 (4.17%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    1
    0
    2
    7
    4
    Device Related Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    Escherichia Urinary Tract Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Eye Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Folliculitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Fungal Skin Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Furuncle
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Gastroenteritis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    1
    0
    Gastroenteritis Viral
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Gastrointestinal Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Genital Candidiasis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Herpes Zoster
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    0
    Hordeolum
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    2 / 72 (2.78%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Infected Fistula
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Infected Skin Ulcer
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Influenza
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    4 / 73 (5.48%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    5
    0
    2
    Keratitis Herpetic
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Laryngitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Localised Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Lower Respiratory Tract Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Lung Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Lyme Disease
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Nail Bed Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Nasopharyngitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    5 / 73 (6.85%)
    2 / 72 (2.78%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    0
    1
    5
    2
    4
    Oesophageal Candidiasis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Oral Candidiasis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    5 / 69 (7.25%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    5
    Oral Fungal Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    Oral Herpes
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    3
    Oral Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Otitis Externa
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Paronychia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    11 / 73 (15.07%)
    6 / 72 (8.33%)
    5 / 69 (7.25%)
         occurrences all number
    0
    0
    0
    0
    25
    10
    9
    Pharyngitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Pharyngotonsillitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Pneumonia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Postoperative Wound Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Pulpitis Dental
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Rash Pustular
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    5
    1
    0
    Rhinitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 73 (0.00%)
    6 / 72 (8.33%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    0
    1
    0
    7
    4
    Sepsis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Severe Acute Respiratory Syndrome
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    1
    Streptococcal Urinary Tract Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Subcutaneous Abscess
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Tinea Pedis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Tonsillitis
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Upper Respiratory Tract Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    6 / 73 (8.22%)
    3 / 72 (4.17%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    0
    0
    7
    4
    4
    Urinary Tract Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    3 / 73 (4.11%)
    6 / 72 (8.33%)
    6 / 69 (8.70%)
         occurrences all number
    1
    0
    1
    1
    7
    8
    7
    Viral Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    3
    Viral Upper Respiratory Tract Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Vulvovaginal Mycotic Infection
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Cachexia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Decreased Appetite
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    3 / 7 (42.86%)
    0 / 3 (0.00%)
    9 / 73 (12.33%)
    11 / 72 (15.28%)
    20 / 69 (28.99%)
         occurrences all number
    1
    1
    3
    0
    11
    15
    36
    Dehydration
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 73 (2.74%)
    3 / 72 (4.17%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    0
    0
    2
    3
    3
    Diabetes Mellitus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    1 / 72 (1.39%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    3
    1
    1
    Hypercalcaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Hypercholesterolaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Hyperglycaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    2 / 72 (2.78%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    0
    0
    4
    5
    5
    Hyperkalaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Hypermagnesaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Hypoalbuminaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    3 / 72 (4.17%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    0
    0
    1
    4
    2
    Hypocalcaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    2 / 3 (66.67%)
    5 / 73 (6.85%)
    11 / 72 (15.28%)
    8 / 69 (11.59%)
         occurrences all number
    0
    1
    0
    2
    6
    29
    12
    Hypoglycaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Hypokalaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    2 / 3 (66.67%)
    4 / 73 (5.48%)
    13 / 72 (18.06%)
    15 / 69 (21.74%)
         occurrences all number
    0
    1
    0
    5
    4
    27
    27
    Hypomagnesaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    2 / 3 (66.67%)
    17 / 73 (23.29%)
    23 / 72 (31.94%)
    14 / 69 (20.29%)
         occurrences all number
    5
    1
    1
    5
    38
    57
    40
    Hyponatraemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    3 / 73 (4.11%)
    2 / 72 (2.78%)
    3 / 69 (4.35%)
         occurrences all number
    0
    1
    0
    0
    4
    3
    4
    Hypophosphataemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    3 / 73 (4.11%)
    1 / 72 (1.39%)
    9 / 69 (13.04%)
         occurrences all number
    0
    0
    0
    1
    4
    1
    19
    Hypoproteinaemia
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    3 / 72 (4.17%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    3
    0
    Iron Deficiency
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Malnutrition
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Plasma Protein Metabolism Disorder
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 73 (0.00%)
    1 / 72 (1.39%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Type 2 Diabetes Mellitus
    alternative dictionary used: MedDRA 15.0
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 73 (1.37%)
    0 / 72 (0.00%)
    0 / 69 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jul 2009
    Following changes were made: - Trial protocol substantially and re-submitted to the competent authorities and ethics committees after completion of the Safety Part to provide transparency on all safety findings during the Safety Part. - Added recommendation for more frequent monitoring of blood values if hepatic impairment occurred during the trial (based on recommended monitoring schedule from the irinotecan summary of product characteristics in subjects with impaired liver function). - Allowed for the safety assessment of subjects withdrawn due to toxicities that were excluded from the DLT definition as part of the consideration to dose-escalate by the safety monitoring committee (SMC). - Included a recommendation to avoid concomitant administration of inhibitors/inducers of CYP4503A4, as these could influence irinotecan metabolism.
    10 Feb 2011
    - Defined the doses for the Randomized Part as 500 and 1000 mg abituzumab. - Increased the number of trial sites from 55 to 70; added Israel as an extra country. - Increased the expected trial duration; the trial would end when 2/3 of the subjects of the Randomized Part experienced death and all subjects stopped treatment. - Changed the frequency of collection of hematology, biochemistry, and coagulation profiles during the Randomization Part. - Changed the details regarding action to be taken with trial drug in the event of an AE, and clarified the AE and SAE reporting period.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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