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    Clinical Trial Results:
    A randomized phase II study of MCS110 combined with carboplatin and gemcitabine in advanced Triple Negative Breast Cancer (TNBC)

    Summary
    EudraCT number
    		 2015-000179-29
    Trial protocol
    		 CZ   DE   AT   ES   BE   FR   IT  
    Global end of trial date
    23 Mar 2020

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

    Trial information

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    Trial identification
    Sponsor protocol code
    CMCS110Z2201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02435680
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
    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
    23 Mar 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Mar 2020
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objective for this trial was to assess the anti-tumor activity of MCS110 combined with carboplatin/gemcitabine, as compared to carboplatin/gemcitabine alone, by comparing progression-free survival (PFS) as per response evaluation criteria in solid tumors (RECIST) (v) 1.1
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Aug 2015
    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
    Australia: 5
    Country: Number of subjects enrolled
    Austria: 4
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Hong Kong: 2
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Korea, Republic of: 4
    Country: Number of subjects enrolled
    Spain: 7
    Country: Number of subjects enrolled
    Taiwan: 1
    Country: Number of subjects enrolled
    Turkey: 1
    Country: Number of subjects enrolled
    United States: 4
    Worldwide total number of subjects
    50
    EEA total number of subjects
    33
    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)
    37
    From 65 to 84 years
    13
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 In total, 50 subjects were enrolled into the study and 49 subjects received study treatment. Number of subjects in Safety Set and PK set was higher than in Full Analysis Set for the MCS110 Arm with additional MCS110 dose on C1D8. Explanations in screening details field.

    Pre-assignment
    Screening details
    		 This was because some subjects received MCS110 dose on C1D8, while it was already instructed to the sites (after first safety review meeting) to omit this dose. These were reported as protocol deviations. - MCS110+carbo+gem PK/safety set:19 - MCS110+C1D8+carbo+gem PK/safety:15 - Carbo/Gem PK/safety:15

    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
    		 MCS110+carboplatin+gemcitabine
    Arm description
    		 experimental
    Arm type
    		 Experimental

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    MCS110
    Other name
    lacnotuzumab
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MCS110 Intravenous (iv) infusion 10, 5 or 2.5 mg/kg Day 1

    Arm title
    		 MCS110 with C1D8 dose+carboplatin+gemcitabine
    Arm description
    		 experimental
    Arm type
    		 Experimental

    Investigational medicinal product name
    MCS110
    Investigational medicinal product code
    MCS110
    Other name
    lacnotuzumab
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    MCS110 Intravenous (iv) infusion 10, 5 or 2.5 mg/kg Day 1 with additional dose on C1D8

    Arm title
    		 carboplatin+gemcitabine
    Arm description
    		 comparator
    Arm type
    		 Active comparator

    Investigational medicinal product name
    carboplatin, gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    - Gemcitabine iv infusion 1000 mg/m2 Days 1 & 8 - Carboplatin iv infusion AUC 2 Days 1 & 8. Area under curve (AUC) 2 dose in milligrams = AUC x (Glomerular filtration rate + 25) according to Calvert’s formula.

    Number of subjects in period 1
    		MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine carboplatin+gemcitabine
    Started
    21
    13
    16
    Completed
    0
    0
    0
    Not completed
    21
    13
    16
         Physician decision
    3
    -
    -
         not treated
    -
    -
    1
         Adverse event, non-fatal
    8
    3
    2
         progressive disease
    10
    7
    11
         subject / guardian decision
    -
    3
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MCS110+carboplatin+gemcitabine
    Reporting group description
    		 experimental

    Reporting group title
    MCS110 with C1D8 dose+carboplatin+gemcitabine
    Reporting group description
    		 experimental

    Reporting group title
    carboplatin+gemcitabine
    Reporting group description
    		 comparator

    Reporting group values
    		 MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine carboplatin+gemcitabine Total
    Number of subjects
    		 21 13 16 50
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 15 10 12 37
        From 65-84 years
    		 6 3 4 13
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 55.5 ± 13.20 56.2 ± 12.97 55.1 ± 13.20 -
    Sex: Female, Male
    Units: participants
        Female
    		 21 13 16 50
        Male
    		 0 0 0 0
    Race/Ethnicity, Customized
    Units: Subjects
        Caucasian
    		 15 10 11 36
        Asian
    		 2 2 3 7
        Unknown
    		 3 1 1 5
        Other
    		 1 0 1 2

    End points

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    End points reporting groups
    Reporting group title
    MCS110+carboplatin+gemcitabine
    Reporting group description
    		 experimental

    Reporting group title
    MCS110 with C1D8 dose+carboplatin+gemcitabine
    Reporting group description
    		 experimental

    Reporting group title
    carboplatin+gemcitabine
    Reporting group description
    		 comparator

    Subject analysis set title
    All MCS110+Carbo+Gem participants
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    experimental

    Subject analysis set title
    gemcitabine+carboplatin
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    comparator

    Subject analysis set title
    MCS110+carbo/gem safety and PK set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    experimental

    Subject analysis set title
    MCS110+C1D8+carbo/gem safety and PK set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    experimental

    Primary: Progression free survival (PFS) as per RECIST v1.1 (by local investigator assessment)

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    End point title
    		 Progression free survival (PFS) as per RECIST v1.1 (by local investigator assessment) [1] [2]
    End point description
    End point type
    Primary
    End point timeframe
    4 years
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: no statistical analysis was performed
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110 with C1D8 dose+carboplatin+gemcitabine carboplatin+gemcitabine All MCS110+Carbo+Gem participants gemcitabine+carboplatin
    Number of subjects analysed
    13 [3]
    16 [4]
    34
    16
    Units: months
    median (confidence interval 90%)
        25th percentile
    0 (0 to 0)
    0 (0 to 0)
    4.3 (1.8 to 4.7)
    3.5 (1.0 to 4.5)
        median
    0 (0 to 0)
    0 (0 to 0)
    5.6 (4.5 to 8.7)
    5.5 (3.5 to 7.5)
        75th percentile
    0 (0 to 0)
    0 (0 to 0)
    10.9 (6.0 to 44.0)
    7.7 (6.4 to 14.5)
    Notes
    [3] - All MCS participants (13 +21) were analyzed together. Refer to the subject analysis set
    [4] - Refer to the subject analysis set
    No statistical analyses for this end point

    Secondary: Free MCS110 : derived Pharmacokinetics (PK) parameters: AUCtau

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    End point title
    		 Free MCS110 : derived Pharmacokinetics (PK) parameters: AUCtau [5]
    End point description
    AUC tau derived from day 0 to 21 (cycle 1) from day 0 to 21 (cycle 4) Cycle duration is 21 days. PK set.
    End point type
    Secondary
    End point timeframe
    day 21 (end cycle 1); day 84 (end cycle 4)
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine
    Number of subjects analysed
    19
    9
    Units: day x microgram / mL
    geometric mean (geometric coefficient of variation)
        day 21
    1430 ± 23.5
    2960 ± 22.7
        day 84
    1840 ± 34.9
    3240 ± 30.0
    No statistical analyses for this end point

    Secondary: Free MCS110 : derived Pharmacokinetics (PK) parameters: Cmax

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    End point title
    		 Free MCS110 : derived Pharmacokinetics (PK) parameters: Cmax [6]
    End point description
    PK set.
    End point type
    Secondary
    End point timeframe
    day 21 (end cycle 1); day 84 (end cycle 4)
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine
    Number of subjects analysed
    18
    12
    Units: microgram / mL
    geometric mean (geometric coefficient of variation)
        day 21
    186 ± 28.5
    281 ± 21.2
        day 84
    240 ± 14.8
    319 ± 27.8
    No statistical analyses for this end point

    Secondary: Cmax derived from Plasma concentration of carboplatin, gemcitabine and 2',2'-difluoro-deoxyuridine (dFdU)

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    End point title
    		 Cmax derived from Plasma concentration of carboplatin, gemcitabine and 2',2'-difluoro-deoxyuridine (dFdU)
    End point description
    day 21 (end cycle 1); day 84 (end cycle 4)
    End point type
    Secondary
    End point timeframe
    day 21, day 84
    End point values
    		 MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine carboplatin+gemcitabine
    Number of subjects analysed
    16
    13
    14
    Units: nanogram /mL
    geometric mean (geometric coefficient of variation)
        Cmax Carboplatin Day 21
    12400 ± 37.3
    12500 ± 33.2
    11200 ± 70.9
        Cmax Carboplatin Day 84
    9550 ± 33.0
    10000 ± 28.9
    11600 ± 55.0
        Cmax Gemcitabine Day 21
    2750 ± 194.5
    5480 ± 95.1
    2370 ± 484.9
        Cmax Gemcitabine Day 84
    2470 ± 227.3
    3400 ± 173.9
    8630 ± 101.2
        Cmax dFdU Day 21
    39100 ± 21.6
    33900 ± 19.5
    37700 ± 28.2
        Cmax dFdU Day 84
    36600 ± 88.6
    30300 ± 11.8
    32300 ± 12.4
    No statistical analyses for this end point

    Secondary: AUClast derived from Plasma concentration of carboplatin, gemcitabine and 2',2'-difluoro-deoxyuridine (dFdU)

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    End point title
    		 AUClast derived from Plasma concentration of carboplatin, gemcitabine and 2',2'-difluoro-deoxyuridine (dFdU)
    End point description
    day 21 (end cycle 1); day 84 (end cycle 4)
    End point type
    Secondary
    End point timeframe
    day 21, day 84
    End point values
    		 MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine carboplatin+gemcitabine
    Number of subjects analysed
    16
    13
    14
    Units: hours * nanogram /mL
    geometric mean (geometric coefficient of variation)
        AUC Carboplatin Day 21
    24500 ± 31.1
    21400 ± 27.3
    21800 ± 56.0
        AUC Carboplatin Day 84
    18300 ± 21.8
    17500 ± 25.0
    20500 ± 34.6
        AUC Gemcitabine Day 21
    2390 ± 157.3
    4270 ± 79.3
    2620 ± 225.5
        AUC Gemcitabine Day 84
    2410 ± 115.2
    2770 ± 118.8
    6320 ± 76.2
        AUC dFdU Day 21
    230000 ± 34.7
    181000 ± 37.7
    231000 ± 25.2
        AUC dFdU Day 84
    229000 ± 31.9
    147000 ± 28.7
    211000 ± 24.7
    No statistical analyses for this end point

    Secondary: Total Colony stimulation factor -1 (CSF-I) circulating levels

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    End point title
    		 Total Colony stimulation factor -1 (CSF-I) circulating levels [7]
    End point description
    results expressed as a the ratio change from baseline expressed in percentage. Absolute values were expressed in pg/mL. Cycle duration is 21 days. Safety set.
    End point type
    Secondary
    End point timeframe
    baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine
    Number of subjects analysed
    16
    13
    Units: % change from baseline
    arithmetic mean (standard deviation)
        Day 1
    110 ± 19.8
    115 ± 34.8
        Day 4
    4930 ± 2280
    4350 ± 1620
        Day 15
    21600 ± 8290
    19500 ± 6130
        Day 22 (cycle 2 day 1)
    32000 ± 9190
    34400 ± 14900
        Day 43 (cycle 3 day 1)
    57900 ± 14100
    70000 ± 27400
        Day 64 (cycle 4 day 1)
    73600 ± 16200
    78000 ± 41200
        Day 85 (cycle 5 day 1)
    79300 ± 27000
    107000 ± 51400
        Day 106 (cycle 6 day 1)
    97500 ± 15600
    103000 ± 50700
        Day 127 (cycle 7 day 1)
    110000 ± 33800
    109000 ± 40100
        Day 148 (cycle 8 day 1)
    108000 ± 30300
    111000 ± 58800
    No statistical analyses for this end point

    Secondary: Serum C-terminal telopeptide of type I collagen (CTX-I)

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    End point title
    		 Serum C-terminal telopeptide of type I collagen (CTX-I) [8]
    End point description
    results expressed as a the ratio change from baseline expressed in percentage. Absolute values were expressed in ng/mL. Cycle duration is 21 days. Safety set.
    End point type
    Secondary
    End point timeframe
    baseline, day 2, 4, 15, 22, 43, 64, 85, 106, 127, 148
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine
    Number of subjects analysed
    18
    12
    Units: % change from baseline
    arithmetic mean (standard deviation)
        Day 2
    79.4 ± 22.8
    85.0 ± 44.0
        Day 4
    72.5 ± 25.4
    80.2 ± 39.6
        Day 15
    65.6 ± 44.3
    69.4 ± 27.4
        Day 22 (cycle 2 day 1)
    67.9 ± 43.6
    52.9 ± 26.5
        Day 43 (cycle 3 day 1)
    64.3 ± 58.7
    39.3 ± 23.8
        Day 64 (cycle 4 day 1)
    69.7 ± 62.2
    29.5 ± 23.7
        Day 85 (cycle 5 day 1)
    102 ± 124
    40.6 ± 34.8
        Day 106 (cycle 6 day 1)
    41.2 ± 13.2
    50.2 ± 45.3
        Day 127 (cycle 7 day 1)
    38.7 ± 14.9
    68.7 ± 66.5
        Day 148 (cycle 8 day 1)
    40.5 ± 13.7
    75.3 ± 103
    No statistical analyses for this end point

    Secondary: Tumor response per RECIST v1.1 (by local investigator assessment)

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    End point title
    		 Tumor response per RECIST v1.1 (by local investigator assessment) [9]
    End point description
    CR: complete response. PR: partial response. SD: stable disease: CBR: clinical benefit rate =CR + PR + SD lasting at least for 6 months. ORR = CR + PR
    End point type
    Secondary
    End point timeframe
    4 years
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110 with C1D8 dose+carboplatin+gemcitabine carboplatin+gemcitabine All MCS110+Carbo+Gem participants gemcitabine+carboplatin
    Number of subjects analysed
    13 [10]
    16 [11]
    34
    16
    Units: participants
        PR
    0
    0
    8
    6
        Non-CR/ Non-progressive disease
    0
    0
    1
    0
        SD
    0
    0
    19
    7
        progressive disease
    0
    0
    4
    1
        unknown
    0
    0
    2
    2
        clinical benefit
    0
    0
    10
    7
        ORR
    0
    0
    8
    6
    Notes
    [10] - All MCS110 participants were analyzed together. Refer to the subject analysis set
    [11] - Refer to the subject analysis set
    No statistical analyses for this end point

    Secondary: Tumor response per RECIST v1.1 (by local investigator assessment) Duration of response

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    End point title
    		 Tumor response per RECIST v1.1 (by local investigator assessment) Duration of response [12]
    End point description
    9.6 months [90% CI: 3.6, 42.5]) as compared Arm 2 (5.0 months [90% CI: 2.7, 13.3]
    End point type
    Secondary
    End point timeframe
    4 years
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110 with C1D8 dose+carboplatin+gemcitabine carboplatin+gemcitabine All MCS110+Carbo+Gem participants gemcitabine+carboplatin
    Number of subjects analysed
    13 [13]
    16 [14]
    34
    16
    Units: months
        median (confidence interval 90%)
    0 (0 to 0)
    0 (0 to 0)
    9.6 (3.6 to 42.5)
    5 (2.7 to 13.3)
    Notes
    [13] - All MCS110 participants (34) were analyzed together. Refer to the subject analysis set
    [14] - Refer to the subject analysis set
    No statistical analyses for this end point

    Secondary: Number of patients with at least one dose reduction, and number of patients with at least one dose interruption

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    End point title
    		 Number of patients with at least one dose reduction, and number of patients with at least one dose interruption [15]
    End point description
    Safety set
    End point type
    Secondary
    End point timeframe
    4 years
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine MCS110+carbo/gem safety and PK set MCS110+C1D8+carbo/gem safety and PK set
    Number of subjects analysed
    21 [16]
    13 [17]
    19
    15
    Units: participants
        MCS110 dose reduction
    0
    0
    3
    5
        MCS110 dose interruption
    0
    0
    6
    9
    Notes
    [16] - please refer to the subject analysis set
    [17] - please refer to the subject analysis set
    No statistical analyses for this end point

    Secondary: Dose intensity

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    End point title
    		 Dose intensity [18]
    End point description
    Relative dose intensity by categories. Safety set.
    End point type
    Secondary
    End point timeframe
    4 years
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine MCS110+carbo/gem safety and PK set MCS110+C1D8+carbo/gem safety and PK set
    Number of subjects analysed
    21 [19]
    13 [20]
    19
    15
    Units: participants
        <50
    0
    0
    1
    4
        50-<75
    0
    0
    8
    3
        75-<90
    0
    0
    7
    5
        90-<110
    0
    0
    3
    3
    Notes
    [19] - please refer to the subject analysis set
    [20] - please refer to the subject analysis set
    No statistical analyses for this end point

    Secondary: Tumor associated macrophage (TAM) and Tumor infiltrating lymphocyte (TIL) content in pre- and post-dose tumor biopsies.

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    End point title
    		 Tumor associated macrophage (TAM) and Tumor infiltrating lymphocyte (TIL) content in pre- and post-dose tumor biopsies. [21]
    End point description
    results expressed as a the ratio change from baseline expressed in percentage: Biopsies were taken at baseline and between Day 29 and Day 43. Safety set.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 29-43
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110+carboplatin+gemcitabine MCS110 with C1D8 dose+carboplatin+gemcitabine
    Number of subjects analysed
    10
    5
    Units: % change from baseline
    geometric mean (geometric coefficient of variation)
        CD163
    42.1 ± 62.1
    43.5 ± 239.5
        CD8
    102 ± 747.3
    99.0 ± 92.2
    No statistical analyses for this end point

    Secondary: Circulating monocytes cells in blood

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    End point title
    		 Circulating monocytes cells in blood [22]
    End point description
    Cycle duration is 21 days results expressed in percentage of cells. Results available for 1 patient only. Safety set.
    End point type
    Secondary
    End point timeframe
    day 15, 29, 43, 50
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: no statistical analysis was performed
    End point values
    		 MCS110 with C1D8 dose+carboplatin+gemcitabine
    Number of subjects analysed
    1
    Units: percentage
    number (not applicable)
        day 15 CD14+CD16-
    43.5
        day 15 CD14+CD16+
    54.8
        day 29 (cycle 2 day 8) CD14+CD16-
    86.6
        day 29 (cycle 2 day 8) CD14+CD16+
    12.2
        day 43 (cycle 3 day 1) CD14+CD16-
    9.1
        day 43 (cycle 3 day 1) CD14+CD16+
    89.7
        day 50 (cycle 3 day 8) CD14+CD16-
    86
        day 50 (cycle 3 day 8) CD14+CD16+
    10
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events and serious adverse events were collected from the first patient first visit until the last patient last visit.
    Adverse event reporting additional description
    AE additional description
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    MCS110 + Carbo/Gem
    Reporting group description
    		 MCS110 + Carbo/Gem

    Reporting group title
    MCS110 with C1D8@dose + Carbo/Gem
    Reporting group description
    		 MCS110 with C1D8@dose + Carbo/Gem

    Reporting group title
    All MCS110 + @Carbo/Gem Patients
    Reporting group description
    		 All MCS110 + @Carbo/Gem Patients

    Reporting group title
    Carbo/Gem
    Reporting group description
    		 Carbo/Gem

    Reporting group title
    All@Patients
    Reporting group description
    		 All@Patients

    Serious adverse events
    		 MCS110 + Carbo/Gem MCS110 with C1D8@dose + Carbo/Gem All MCS110 + @Carbo/Gem Patients Carbo/Gem All@Patients
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 19 (52.63%)
    7 / 15 (46.67%)
    17 / 34 (50.00%)
    1 / 15 (6.67%)
    18 / 49 (36.73%)
         number of deaths (all causes)
    1
    1
    2
    1
    3
         number of deaths resulting from adverse events
    1
    1
    2
    0
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour associated fever
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 15 (13.33%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    1 / 4
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial ischaemia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical haemolytic uraemic syndrome
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 19 (0.00%)
    3 / 15 (20.00%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
    4 / 4
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstructive pancreatitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 15 (13.33%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    2 / 2
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    2 / 2
    0 / 0
    2 / 2
    Infections and infestations
    Device related infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mastitis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 MCS110 + Carbo/Gem MCS110 with C1D8@dose + Carbo/Gem All MCS110 + @Carbo/Gem Patients Carbo/Gem All@Patients
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    19 / 19 (100.00%)
    15 / 15 (100.00%)
    34 / 34 (100.00%)
    15 / 15 (100.00%)
    49 / 49 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Vascular disorders
    Flushing
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    1 / 15 (6.67%)
    2 / 49 (4.08%)
         occurrences all number
    2
    0
    2
    1
    3
    Haematoma
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    2
    0
    2
    0
    2
    Hot flush
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Hypertension
         subjects affected / exposed
    3 / 19 (15.79%)
    1 / 15 (6.67%)
    4 / 34 (11.76%)
    0 / 15 (0.00%)
    4 / 49 (8.16%)
         occurrences all number
    3
    5
    8
    0
    8
    Hypotension
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Peripheral venous disease
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Phlebitis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Poor venous access
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Thrombophlebitis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    2 / 15 (13.33%)
    2 / 49 (4.08%)
         occurrences all number
    0
    0
    0
    2
    2
    Thrombosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    5 / 19 (26.32%)
    3 / 15 (20.00%)
    8 / 34 (23.53%)
    4 / 15 (26.67%)
    12 / 49 (24.49%)
         occurrences all number
    8
    4
    12
    6
    18
    Chest discomfort
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Chills
         subjects affected / exposed
    2 / 19 (10.53%)
    2 / 15 (13.33%)
    4 / 34 (11.76%)
    0 / 15 (0.00%)
    4 / 49 (8.16%)
         occurrences all number
    2
    2
    4
    0
    4
    Device related thrombosis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Face oedema
         subjects affected / exposed
    4 / 19 (21.05%)
    3 / 15 (20.00%)
    7 / 34 (20.59%)
    0 / 15 (0.00%)
    7 / 49 (14.29%)
         occurrences all number
    5
    3
    8
    0
    8
    Facial pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Fatigue
         subjects affected / exposed
    6 / 19 (31.58%)
    9 / 15 (60.00%)
    15 / 34 (44.12%)
    4 / 15 (26.67%)
    19 / 49 (38.78%)
         occurrences all number
    6
    11
    17
    7
    24
    Gait disturbance
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    General physical health deterioration
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Influenza like illness
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    1 / 15 (6.67%)
    2 / 49 (4.08%)
         occurrences all number
    0
    2
    2
    1
    3
    Infusion site extravasation
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Infusion site pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Injection site reaction
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Injection site swelling
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Oedema peripheral
         subjects affected / exposed
    3 / 19 (15.79%)
    4 / 15 (26.67%)
    7 / 34 (20.59%)
    1 / 15 (6.67%)
    8 / 49 (16.33%)
         occurrences all number
    4
    4
    8
    1
    9
    Peripheral swelling
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    2
    3
    0
    3
    Pyrexia
         subjects affected / exposed
    4 / 19 (21.05%)
    3 / 15 (20.00%)
    7 / 34 (20.59%)
    2 / 15 (13.33%)
    9 / 49 (18.37%)
         occurrences all number
    4
    5
    9
    3
    12
    Swelling
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Swelling face
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 15 (0.00%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    2
    0
    2
    0
    2
    Xerosis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Hypersensitivity
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    2 / 15 (13.33%)
    3 / 49 (6.12%)
         occurrences all number
    0
    1
    1
    3
    4
    Reproductive system and breast disorders
    Breast oedema
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Breast pain
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 15 (13.33%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    1
    2
    3
    0
    3
    Menorrhagia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Pelvic pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Aphonia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Apnoea
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Bronchospasm
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Cough
         subjects affected / exposed
    3 / 19 (15.79%)
    4 / 15 (26.67%)
    7 / 34 (20.59%)
    0 / 15 (0.00%)
    7 / 49 (14.29%)
         occurrences all number
    4
    4
    8
    0
    8
    Dysphonia
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 15 (6.67%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    2
    1
    3
    0
    3
    Dyspnoea
         subjects affected / exposed
    6 / 19 (31.58%)
    5 / 15 (33.33%)
    11 / 34 (32.35%)
    2 / 15 (13.33%)
    13 / 49 (26.53%)
         occurrences all number
    7
    7
    14
    2
    16
    Epistaxis
         subjects affected / exposed
    1 / 19 (5.26%)
    3 / 15 (20.00%)
    4 / 34 (11.76%)
    0 / 15 (0.00%)
    4 / 49 (8.16%)
         occurrences all number
    1
    8
    9
    0
    9
    Hypoxia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Nasal congestion
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Pharyngeal oedema
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Pleural effusion
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Productive cough
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Pulmonary oedema
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 15 (0.00%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    2
    0
    2
    0
    2
    Snoring
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    2
    0
    2
    0
    2
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Vocal cord polyp
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 19 (10.53%)
    2 / 15 (13.33%)
    4 / 34 (11.76%)
    1 / 15 (6.67%)
    5 / 49 (10.20%)
         occurrences all number
    2
    2
    4
    1
    5
    Depressed mood
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    2
    0
    2
    Depression
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    2 / 15 (13.33%)
    3 / 49 (6.12%)
         occurrences all number
    2
    0
    2
    2
    4
    Hallucination
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Insomnia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    1 / 15 (6.67%)
    2 / 49 (4.08%)
         occurrences all number
    2
    0
    2
    1
    3
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    12 / 19 (63.16%)
    12 / 15 (80.00%)
    24 / 34 (70.59%)
    2 / 15 (13.33%)
    26 / 49 (53.06%)
         occurrences all number
    17
    16
    33
    4
    37
    Amylase increased
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    2
    3
    0
    3
    Aspartate aminotransferase increased
         subjects affected / exposed
    16 / 19 (84.21%)
    12 / 15 (80.00%)
    28 / 34 (82.35%)
    4 / 15 (26.67%)
    32 / 49 (65.31%)
         occurrences all number
    22
    13
    35
    8
    43
    Blood alkaline phosphatase increased
         subjects affected / exposed
    4 / 19 (21.05%)
    1 / 15 (6.67%)
    5 / 34 (14.71%)
    0 / 15 (0.00%)
    5 / 49 (10.20%)
         occurrences all number
    4
    1
    5
    0
    5
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    9 / 19 (47.37%)
    7 / 15 (46.67%)
    16 / 34 (47.06%)
    0 / 15 (0.00%)
    16 / 49 (32.65%)
         occurrences all number
    9
    8
    17
    0
    17
    Blood creatinine increased
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 15 (13.33%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    1
    2
    3
    0
    3
    Blood iron decreased
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 15 (6.67%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    2
    1
    3
    0
    3
    C-reactive protein increased
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    5 / 19 (26.32%)
    1 / 15 (6.67%)
    6 / 34 (17.65%)
    0 / 15 (0.00%)
    6 / 49 (12.24%)
         occurrences all number
    5
    1
    6
    0
    6
    Haemoglobin decreased
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    2
    0
    2
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    3
    0
    3
    0
    3
    Lipase
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Lipase increased
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 15 (6.67%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    3
    1
    4
    0
    4
    Neutrophil count decreased
         subjects affected / exposed
    6 / 19 (31.58%)
    5 / 15 (33.33%)
    11 / 34 (32.35%)
    5 / 15 (33.33%)
    16 / 49 (32.65%)
         occurrences all number
    16
    21
    37
    13
    50
    Platelet count decreased
         subjects affected / exposed
    3 / 19 (15.79%)
    3 / 15 (20.00%)
    6 / 34 (17.65%)
    6 / 15 (40.00%)
    12 / 49 (24.49%)
         occurrences all number
    9
    28
    37
    12
    49
    Weight decreased
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    2
    3
    0
    3
    Weight increased
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 15 (13.33%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    0
    2
    2
    0
    2
    White blood cell count decreased
         subjects affected / exposed
    3 / 19 (15.79%)
    4 / 15 (26.67%)
    7 / 34 (20.59%)
    1 / 15 (6.67%)
    8 / 49 (16.33%)
         occurrences all number
    7
    7
    14
    2
    16
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Chemical cystitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Contusion
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 15 (6.67%)
    3 / 34 (8.82%)
    1 / 15 (6.67%)
    4 / 49 (8.16%)
         occurrences all number
    2
    1
    3
    1
    4
    Humerus fracture
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Oral contusion
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Post procedural haematoma
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Seroma
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    3
    0
    3
    0
    3
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Bradycardia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Palpitations
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    1 / 15 (6.67%)
    2 / 49 (4.08%)
         occurrences all number
    1
    0
    1
    1
    2
    Tachycardia
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    2
    0
    2
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Balance disorder
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Dizziness
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 15 (13.33%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    0
    5
    5
    0
    5
    Dysaesthesia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Dysgeusia
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    2
    0
    2
    Headache
         subjects affected / exposed
    4 / 19 (21.05%)
    3 / 15 (20.00%)
    7 / 34 (20.59%)
    4 / 15 (26.67%)
    11 / 49 (22.45%)
         occurrences all number
    11
    3
    14
    7
    21
    Myelopathy
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Neuralgia
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 15 (0.00%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    3
    0
    3
    0
    3
    Neuropathy peripheral
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    1 / 15 (6.67%)
    2 / 49 (4.08%)
         occurrences all number
    0
    1
    1
    1
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 19 (0.00%)
    3 / 15 (20.00%)
    3 / 34 (8.82%)
    1 / 15 (6.67%)
    4 / 49 (8.16%)
         occurrences all number
    0
    3
    3
    1
    4
    Vocal cord paralysis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    13 / 19 (68.42%)
    10 / 15 (66.67%)
    23 / 34 (67.65%)
    10 / 15 (66.67%)
    33 / 49 (67.35%)
         occurrences all number
    22
    27
    49
    16
    65
    Leukocytosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    2
    0
    2
    0
    2
    Leukopenia
         subjects affected / exposed
    1 / 19 (5.26%)
    5 / 15 (33.33%)
    6 / 34 (17.65%)
    3 / 15 (20.00%)
    9 / 49 (18.37%)
         occurrences all number
    4
    12
    16
    5
    21
    Neutropenia
         subjects affected / exposed
    10 / 19 (52.63%)
    8 / 15 (53.33%)
    18 / 34 (52.94%)
    8 / 15 (53.33%)
    26 / 49 (53.06%)
         occurrences all number
    24
    20
    44
    21
    65
    Thrombocytopenia
         subjects affected / exposed
    8 / 19 (42.11%)
    8 / 15 (53.33%)
    16 / 34 (47.06%)
    8 / 15 (53.33%)
    24 / 49 (48.98%)
         occurrences all number
    16
    18
    34
    16
    50
    Thrombotic thrombocytopenic purpura
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    2
    0
    2
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    3
    3
    0
    3
    Diplopia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Dry eye
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Eye oedema
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Eye pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Eyelid oedema
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 15 (0.00%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    3
    0
    3
    0
    3
    Foreign body sensation in eyes
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Lacrimation increased
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 15 (6.67%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    2
    1
    3
    0
    3
    Orbital oedema
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Periorbital oedema
         subjects affected / exposed
    8 / 19 (42.11%)
    6 / 15 (40.00%)
    14 / 34 (41.18%)
    0 / 15 (0.00%)
    14 / 49 (28.57%)
         occurrences all number
    8
    8
    16
    0
    16
    Periorbital swelling
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Vision blurred
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    2
    0
    2
    Xerophthalmia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Abdominal pain
         subjects affected / exposed
    4 / 19 (21.05%)
    3 / 15 (20.00%)
    7 / 34 (20.59%)
    1 / 15 (6.67%)
    8 / 49 (16.33%)
         occurrences all number
    6
    3
    9
    3
    12
    Abdominal pain upper
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 15 (6.67%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    2
    2
    4
    0
    4
    Chapped lips
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Constipation
         subjects affected / exposed
    5 / 19 (26.32%)
    3 / 15 (20.00%)
    8 / 34 (23.53%)
    2 / 15 (13.33%)
    10 / 49 (20.41%)
         occurrences all number
    15
    5
    20
    2
    22
    Diarrhoea
         subjects affected / exposed
    5 / 19 (26.32%)
    2 / 15 (13.33%)
    7 / 34 (20.59%)
    3 / 15 (20.00%)
    10 / 49 (20.41%)
         occurrences all number
    6
    4
    10
    4
    14
    Dry mouth
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 15 (0.00%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    2
    0
    2
    0
    2
    Dyspepsia
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 15 (6.67%)
    3 / 34 (8.82%)
    3 / 15 (20.00%)
    6 / 49 (12.24%)
         occurrences all number
    6
    1
    7
    3
    10
    Flatulence
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Gastritis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    2
    2
    0
    2
    Gingival bleeding
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    3
    4
    0
    4
    Gingival pain
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Gingival recession
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Lip oedema
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Nausea
         subjects affected / exposed
    10 / 19 (52.63%)
    12 / 15 (80.00%)
    22 / 34 (64.71%)
    8 / 15 (53.33%)
    30 / 49 (61.22%)
         occurrences all number
    14
    22
    36
    15
    51
    Odynophagia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Periodontal disease
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    1 / 15 (6.67%)
    2 / 49 (4.08%)
         occurrences all number
    0
    1
    1
    1
    2
    Rectal haemorrhage
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Salivary hypersecretion
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Stomatitis
         subjects affected / exposed
    2 / 19 (10.53%)
    5 / 15 (33.33%)
    7 / 34 (20.59%)
    1 / 15 (6.67%)
    8 / 49 (16.33%)
         occurrences all number
    3
    8
    11
    1
    12
    Vomiting
         subjects affected / exposed
    5 / 19 (26.32%)
    3 / 15 (20.00%)
    8 / 34 (23.53%)
    2 / 15 (13.33%)
    10 / 49 (20.41%)
         occurrences all number
    9
    4
    13
    3
    16
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 15 (13.33%)
    3 / 34 (8.82%)
    3 / 15 (20.00%)
    6 / 49 (12.24%)
         occurrences all number
    1
    2
    3
    3
    6
    Blood blister
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Dermatitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Dermatitis acneiform
         subjects affected / exposed
    0 / 19 (0.00%)
    3 / 15 (20.00%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    0
    3
    3
    0
    3
    Dry skin
         subjects affected / exposed
    2 / 19 (10.53%)
    2 / 15 (13.33%)
    4 / 34 (11.76%)
    0 / 15 (0.00%)
    4 / 49 (8.16%)
         occurrences all number
    2
    2
    4
    0
    4
    Erythema
         subjects affected / exposed
    0 / 19 (0.00%)
    3 / 15 (20.00%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    0
    3
    3
    0
    3
    Hyperhidrosis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Nail disorder
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Pruritus
         subjects affected / exposed
    2 / 19 (10.53%)
    3 / 15 (20.00%)
    5 / 34 (14.71%)
    0 / 15 (0.00%)
    5 / 49 (10.20%)
         occurrences all number
    3
    3
    6
    0
    6
    Purpura
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Rash
         subjects affected / exposed
    5 / 19 (26.32%)
    5 / 15 (33.33%)
    10 / 34 (29.41%)
    4 / 15 (26.67%)
    14 / 49 (28.57%)
         occurrences all number
    7
    8
    15
    6
    21
    Rash maculo-papular
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    2
    0
    2
    Rash pruritic
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Skin fissures
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Skin lesion
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Stasis dermatitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Toxic skin eruption
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Dysuria
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Nocturia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 15 (0.00%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    2
    0
    2
    0
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 15 (0.00%)
    2 / 34 (5.88%)
    1 / 15 (6.67%)
    3 / 49 (6.12%)
         occurrences all number
    2
    0
    2
    1
    3
    Back pain
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    2 / 15 (13.33%)
    4 / 49 (8.16%)
         occurrences all number
    1
    2
    3
    2
    5
    Bone pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Fracture pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Joint swelling
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Muscle spasms
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    1 / 15 (6.67%)
    2 / 49 (4.08%)
         occurrences all number
    1
    0
    1
    1
    2
    Muscular weakness
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Myalgia
         subjects affected / exposed
    3 / 19 (15.79%)
    1 / 15 (6.67%)
    4 / 34 (11.76%)
    1 / 15 (6.67%)
    5 / 49 (10.20%)
         occurrences all number
    4
    1
    5
    1
    6
    Neck pain
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    2
    0
    2
    Pain in extremity
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 15 (6.67%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    2
    1
    3
    0
    3
    Soft tissue necrosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Tendonitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Infections and infestations
    Bronchitis viral
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Candida infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Catheter site infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Cellulitis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Cystitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Ear infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Folliculitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Fungal oesophagitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Gingivitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Influenza
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Lymphangitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Mastitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Nail infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Oral candidiasis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    1 / 15 (6.67%)
    2 / 49 (4.08%)
         occurrences all number
    4
    0
    4
    1
    5
    Oral herpes
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    2 / 15 (13.33%)
    4 / 49 (8.16%)
         occurrences all number
    1
    1
    2
    2
    4
    Oral infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Oropharyngeal candidiasis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 15 (13.33%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    0
    3
    3
    0
    3
    Sinusitis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    1 / 15 (6.67%)
    2 / 49 (4.08%)
         occurrences all number
    0
    3
    3
    1
    4
    Spinal cord infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Tinea pedis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 15 (0.00%)
    0 / 34 (0.00%)
    1 / 15 (6.67%)
    1 / 49 (2.04%)
         occurrences all number
    0
    0
    0
    1
    1
    Tonsillitis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    4
    4
    0
    4
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 15 (13.33%)
    3 / 34 (8.82%)
    2 / 15 (13.33%)
    5 / 49 (10.20%)
         occurrences all number
    2
    3
    5
    4
    9
    Urinary tract infection
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 15 (13.33%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    2
    2
    4
    0
    4
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 19 (15.79%)
    4 / 15 (26.67%)
    7 / 34 (20.59%)
    2 / 15 (13.33%)
    9 / 49 (18.37%)
         occurrences all number
    3
    5
    8
    2
    10
    Dehydration
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    0
    1
    1
    0
    1
    Fluid retention
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Hypercalcaemia
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 15 (0.00%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    2
    0
    2
    0
    2
    Hyperglycaemia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 15 (0.00%)
    1 / 34 (2.94%)
    0 / 15 (0.00%)
    1 / 49 (2.04%)
         occurrences all number
    1
    0
    1
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 15 (6.67%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    1
    1
    2
    0
    2
    Hypocalcaemia
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 15 (0.00%)
    2 / 34 (5.88%)
    0 / 15 (0.00%)
    2 / 49 (4.08%)
         occurrences all number
    2
    0
    2
    0
    2
    Hypokalaemia
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 15 (6.67%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    2
    1
    3
    0
    3
    Hypomagnesaemia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 15 (6.67%)
    1 / 34 (2.94%)
    1 / 15 (6.67%)
    2 / 49 (4.08%)
         occurrences all number
    0
    1
    1
    1
    2
    Hyponatraemia
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 15 (6.67%)
    3 / 34 (8.82%)
    0 / 15 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    2
    1
    3
    0
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Mar 2015
    The main reason for this amendment is to add more specific guidance for dose modifications for creatine kinase elevation suspected to be related to MCS110, following Health Authority feed-back. Furthermore, a clarification has been added regarding severe periorbital edema
    08 Apr 2016
    The main purpose of this amendment is to provide additional flexibility for MCS110 dosing by introducing the option to skip the additional MCS110 dose on C1D8 for subsequent patients, should any safety concerns be revealed upon review of data from the dosing regimen currently being evaluated.
    20 Sep 2016
    The main purpose of this amendment is to extend the post-treatment contraception period from 60 to 90 days for patients receiving MCS110. In addition, the safety follow-up has been extended from 60 to 90 days
    04 May 2017
    The purpose of this amendment is to address requested changes from a Health Authority regarding the post-treatment contraception period for carboplatin and gemcitabine. The minimum required post-treatment contraception period has been revised and updated to 30 days.
    11 Oct 2017
    Following the recruitment halt, the purpose of this amendment is to reduce the schedule of assessments while still ensuring adequate safety monitoring in order to reduce the burden to patients who remain on study treatment.
    08 Oct 2018
    The main purpose of this amendment is to allow safety monitoring of creatine kinase elevations per local guidelines, to modify the language on Tumor associated macrophages content for patient selection, and to implement requested changes from Health Authorities.

    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.
    Enrollment in the study was terminated early as a result of challenges in enrollment due to the rapid evolution of the therapeutic landscape, and was not as a consequence of any safety concern. Ongoing patients continued according to the protocol.
    For support, Contact us.
    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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