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    Clinical Trial Results:
    First-In-Human, Dose Escalating Safety Study of Tissue Factor Specific Antibody-Drug Conjugate Tisotumab Vedotin (Humax®-TF-ADC) in Patients with Locally Advanced and/or Metastatic Solid Tumors Known to Express Tissue Factor

    Summary
    EudraCT number
    2013-001074-15
    Trial protocol
    GB  
    Global end of trial date
    02 May 2019

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

    Trial information

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    Trial identification
    Sponsor protocol code
    GEN701
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02001623
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Genmab A/S
    Sponsor organisation address
    Kalvebod Brygge 43, Copenhagen, Denmark, DK-1560
    Public contact
    Clinical Trial Information, Genmab A/S, +45 70202728, clinicaltrials@genmab.com
    Scientific contact
    Clinical Trial Information, Genmab A/S, +45 70202728, clinicaltrials@genmab.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
    02 May 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 May 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the trial was to establish the tolerability of tisotumab vedotin in a mixed population of participants with specified solid tumors.
    Protection of trial subjects
    The trial was conducted in accordance with the protocol and amendments, the International Council for Harmonisation E6 guideline for Good Clinical Practice, applicable local regulations, and ethical principles that have their origins in the Declaration of Helsinki. In addition, the trial was conducted in accordance with FDA 21 Code of Federal Regulations parts 312, 50, and 56, and the directive 2001/20/EC of the European Parliament.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    02 Dec 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 33
    Country: Number of subjects enrolled
    Belgium: 35
    Country: Number of subjects enrolled
    Denmark: 29
    Country: Number of subjects enrolled
    Sweden: 6
    Country: Number of subjects enrolled
    United Kingdom: 92
    Worldwide total number of subjects
    195
    EEA total number of subjects
    70
    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)
    138
    From 65 to 84 years
    57
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    In the dose escalation part of the study, 40 participants were screened and 27 were enrolled and received treatment. In the dose expansion part of the study, 294 participants were screened and 168 were enrolled and received treatment.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Dose Escalation Part
    Arm description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days; 1Q3W) for four cycles (12 weeks total). After four cycles, if there was evidence of the participant benefiting from treatment, at the discretion of the treating physician, there was an option to continue in the study for up to a maximum of eight additional cycles (24 weeks) or until unacceptable toxicity was observed (maximum treatment duration: 36 weeks total).
    Arm type
    Experimental

    Investigational medicinal product name
    Tisotumab Vedotin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tisotumab vedotin was administered as an intravenous (IV) infusion at doses 0.3, 0.6, 0.9, 1.2, 1.5, 1.8, 2.0 and 2.2 mg/kg.

    Arm title
    Dose Expansion Part
    Arm description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days; 1Q3W) for four cycles (12 weeks total). After four cycles, if there was evidence of the participant benefiting from treatment, at the discretion of the treating physician, there was an option to continue in the study for up to a maximum of eight additional cycles (24 weeks) or until unacceptable toxicity was observed (maximum treatment duration: 36 weeks total).
    Arm type
    Experimental

    Investigational medicinal product name
    Tisotumab Vedotin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tisotumab vedotin was administered as an IV infusion at a dose of 2.0 mg/kg.

    Number of subjects in period 1
    Dose Escalation Part Dose Expansion Part
    Started
    27
    168
    Completed 4 cycles of treatment
    9
    81
    Completed 12 cycles of treatment
    2
    5
    Completed
    2
    5
    Not completed
    25
    163
         Disease Progression
    19
    92
         Dose limiting toxicity
    1
    -
         Physician decision
    -
    18
         Adverse event, serious fatal
    1
    -
         Adverse event, non-fatal
    3
    35
         Other - miscellaneous
    -
    1
         Consent withdrawn by subject
    1
    16
         Lost to follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Dose Escalation Part
    Reporting group description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days; 1Q3W) for four cycles (12 weeks total). After four cycles, if there was evidence of the participant benefiting from treatment, at the discretion of the treating physician, there was an option to continue in the study for up to a maximum of eight additional cycles (24 weeks) or until unacceptable toxicity was observed (maximum treatment duration: 36 weeks total).

    Reporting group title
    Dose Expansion Part
    Reporting group description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days; 1Q3W) for four cycles (12 weeks total). After four cycles, if there was evidence of the participant benefiting from treatment, at the discretion of the treating physician, there was an option to continue in the study for up to a maximum of eight additional cycles (24 weeks) or until unacceptable toxicity was observed (maximum treatment duration: 36 weeks total).

    Reporting group values
    Dose Escalation Part Dose Expansion Part Total
    Number of subjects
    27 168 195
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    20 118 138
        From 65-84 years
    7 50 57
        85 years and over
    0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    62 (43 to 73) 58 (21 to 79) -
    Gender categorical
    Units: Subjects
        Female
    18 122 140
        Male
    9 46 55
    Race
    Units: Subjects
        White
    27 155 182
        Black or African American
    0 2 2
        Asian
    0 5 5
        Native Hawaiian or other Pacific Islander
    0 1 1
        Other
    0 2 2
        Missing
    0 3 3
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    0 2 2
        Not Hispanic or Latino
    27 164 191
        Missing
    0 2 2

    End points

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    End points reporting groups
    Reporting group title
    Dose Escalation Part
    Reporting group description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days; 1Q3W) for four cycles (12 weeks total). After four cycles, if there was evidence of the participant benefiting from treatment, at the discretion of the treating physician, there was an option to continue in the study for up to a maximum of eight additional cycles (24 weeks) or until unacceptable toxicity was observed (maximum treatment duration: 36 weeks total).

    Reporting group title
    Dose Expansion Part
    Reporting group description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days; 1Q3W) for four cycles (12 weeks total). After four cycles, if there was evidence of the participant benefiting from treatment, at the discretion of the treating physician, there was an option to continue in the study for up to a maximum of eight additional cycles (24 weeks) or until unacceptable toxicity was observed (maximum treatment duration: 36 weeks total).

    Subject analysis set title
    Dose Escalation Part: 0.3 mg/kg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.3 mg/kg of body weight.

    Subject analysis set title
    Dose Escalation Part: 0.6 mg/kg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight.

    Subject analysis set title
    Dose Escalation Part: 0.9 mg/kg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight.

    Subject analysis set title
    Dose Escalation Part: 1.2 mg/kg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight.

    Subject analysis set title
    Dose Escalation Part: 1.5 mg/kg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight.

    Subject analysis set title
    Dose Escalation Part: 1.8 mg/kg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight.

    Subject analysis set title
    Dose Escalation Part: 2.0 mg/kg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.

    Subject analysis set title
    Dose Escalation Part: 2.2 mg/kg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight.

    Subject analysis set title
    Dose Expansion Part: Bladder Cancer
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.

    Subject analysis set title
    Dose Expansion Part: Cervical Cancer
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.

    Subject analysis set title
    Dose Expansion Part: Endometrial Cancer
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.

    Subject analysis set title
    Dose Expansion Part: Esophageal Cancer
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.

    Subject analysis set title
    Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.

    Subject analysis set title
    Dose Expansion Part: Ovarian Cancer
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.

    Subject analysis set title
    Dose Expansion Part: Prostate Cancer
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.

    Subject analysis set title
    Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    The PK analysis set includes all participants in the dose expansion who had been exposed to tisotumab vedotin and had at least one PK assessment after the first dose.

    Primary: Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events

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    End point title
    Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events [1]
    End point description
    Evaluation of treatment-emergent adverse events (AEs) includes number of participants with at least one: AE Serious adverse event (SAE) Infusion-related AE Common Terminology Criteria for Adverse Events (CTCAE) grade >=3 Treatment-related AE
    End point type
    Primary
    End point timeframe
    Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The exposure ranged from 1 to 249 days in the escalation part.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics were planned for this endpoint
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    Units: Participants
        AEs
    3
    3
    3
    3
    3
    3
    3
    6
        SAEs
    2
    1
    0
    2
    2
    2
    2
    4
        Infusion-Related AEs
    1
    0
    0
    0
    0
    0
    0
    0
        CTCAE Grade >=3 AEs
    2
    3
    1
    1
    2
    3
    2
    4
        AEs Related to Study Drug
    3
    3
    2
    3
    3
    3
    3
    6
    No statistical analyses for this end point

    Primary: Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events

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    End point title
    Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events [2]
    End point description
    Evaluation of treatment-emergent adverse events (AEs) includes number of participants with at least one: AE Serious adverse event (SAE) Infusion-related AE Common terminology criteria for adverse events (CTCAE) grade >=3 Treatment-related AE
    End point type
    Primary
    End point timeframe
    Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The exposure ranged from 1 to 325 days in the expansion part.
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics were planned for this endpoint
    End point values
    Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    15
    55
    14
    15
    15
    36
    18
    Units: Participants
        AEs
    15
    55
    14
    15
    15
    36
    18
        SAEs
    7
    26
    5
    8
    6
    13
    6
        Infusion-Related AEs
    1
    1
    1
    1
    2
    0
    0
        CTCAE Grade >=3 AEs
    9
    30
    8
    8
    10
    16
    11
        AEs Related to Study Drug
    15
    54
    13
    14
    14
    36
    18
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Number of Participants with Markedly Abnormal Hematology Values

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    End point title
    Dose Escalation and Expansion Part: Number of Participants with Markedly Abnormal Hematology Values
    End point description
    Number of participants with markedly abnormal hematology results were defined as all participants who experienced at least 1 CTCAE grade >= 3 hematology value.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    15
    55
    14
    15
    15
    36
    18
    Units: participants
    2
    1
    1
    0
    2
    2
    0
    1
    0
    23
    0
    3
    1
    5
    3
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Parts: Number of Participants with Markedly Abnormal Coagulation Values

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    End point title
    Dose Escalation and Expansion Parts: Number of Participants with Markedly Abnormal Coagulation Values
    End point description
    Number of participants with markedly abnormal coagulation results were defined as all participants who experienced at least 1 CTCAE grade >= 3 coagulation value.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    15
    55
    14
    15
    15
    36
    18
    Units: participants
    0
    0
    0
    0
    0
    0
    0
    1
    1
    7
    2
    0
    2
    5
    4
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Number of Participants with Markedly Abnormal Biochemistry Values

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    End point title
    Dose Escalation and Expansion Part: Number of Participants with Markedly Abnormal Biochemistry Values
    End point description
    Number of participants with markedly abnormal biochemistry results were defined as all participants who experienced at least 1 CTCAE grade >= 3 biochemistry value.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    15
    55
    14
    15
    15
    36
    18
    Units: participants
    2
    1
    3
    0
    1
    0
    1
    2
    4
    8
    4
    6
    2
    9
    4
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash

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    End point title
    Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    15
    55
    14
    15
    15
    36
    18
    Units: Participants
    1
    0
    0
    2
    0
    2
    2
    4
    3
    6
    2
    2
    2
    8
    5
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event

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    End point title
    Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event
    End point description
    Bleeding adverse events of special interest included treatment emergent adverse events with preferred terms within the following standardised MedDRA queries: Haemorrhage terms, excluding laboratory terms SMQ [20000039] (Broad) and Haemorrhage, laboratory terms SMQ [20000040] (Narrow). Bleeding adverse events of special interest were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) and were graded from 1 to 5, where 1 indicated a mild event and 5 indicated a fatal event. Bleeding events of all grades are included in the numbers below.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    15
    55
    14
    15
    15
    36
    18
    Units: Participants
    0
    1
    0
    3
    3
    3
    2
    5
    10
    31
    10
    7
    9
    27
    10
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Number of Participants Who Experienced a Neuropathy Event

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    End point title
    Dose Escalation and Expansion Part: Number of Participants Who Experienced a Neuropathy Event
    End point description
    Peripheral neuropathy events of special interest were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) and were graded from 1 to 5, where 1 indicated a mild event and 5 indicated a fatal event. Peripheral neuropathy events of all grades are included in the numbers below.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    15
    55
    14
    15
    15
    36
    18
    Units: Participants
    0
    1
    1
    1
    0
    1
    0
    1
    5
    17
    6
    3
    5
    17
    7
    No statistical analyses for this end point

    Secondary: Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF

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    End point title
    Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. Data was not planned to be collected for the clearance of tisotumab vedotin and total HuMax-TF. 99999 = no evaluable data. 99999 is presented when no participants had evaluable data or only 1 participant had evaluable data, so geometric coefficient of variation could not be calculated.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Number of subjects analysed
    0 [3]
    3 [4]
    3
    3
    3
    3 [5]
    3 [6]
    5 [7]
    Units: mL/hr/kg
    geometric mean (geometric coefficient of variation)
        Tisotumab Vedotin: Cycle 1
    ±
    1.61 ± 7.79
    1.46 ± 15.23
    1.07 ± 11.60
    1.84 ± 20.59
    1.17 ± 60.05
    1.56 ± 34.12
    0.87 ± 8.93
        Tisotumab Vedotin: Cycle 2
    ±
    1.72 ± 4.98
    1.44 ± 6.32
    1.07 ± 10.45
    2.05 ± 26.80
    0.93 ± 24.03
    1.30 ± 19.06
    1.03 ± 11.34
        Total HuMax-TF: Cycle 1
    ±
    1.02 ± 0.20
    0.98 ± 16.90
    0.69 ± 12.61
    1.26 ± 31.29
    0.81 ± 69.72
    0.87 ± 33.85
    0.56 ± 14.13
        Total HuMax-TF: Cycle 2
    ±
    1.05 ± 9.95
    0.98 ± 6.52
    0.71 ± 13.41
    1.40 ± 31.39
    0.53 ± 12.41
    0.82 ± 26.45
    0.61 ± 9.72
    Notes
    [3] - No evaluable PK assessments
    [4] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 1 N = 2 Total HuMax-TF Cycle 2 N = 2
    [5] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 2 N = 2
    [6] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 2 N = 2
    [7] - Tisotumab Vedotin Cycle 2 N = 3 Total HuMax-TF Cycle 2 N = 3
    No statistical analyses for this end point

    Secondary: Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF

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    End point title
    Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. Data was not planned to be collected for the volume of distribution of tisotumab vedotin and total HuMax-TF for the dose expansion part. 99999 = no evaluable data. 99999 is presented when no participants had evaluable data or only 1 participant had evaluable data, so geometric coefficient of variation could not be calculated.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Number of subjects analysed
    0 [8]
    3 [9]
    3
    3
    3
    3 [10]
    3 [11]
    5 [12]
    Units: mL/kg
    geometric mean (geometric coefficient of variation)
        Tisotumab Vedotin: Cycle 1
    ±
    68.40 ± 11.84
    70.80 ± 14.54
    63.46 ± 16.87
    86.10 ± 12.38
    81.13 ± 35.60
    92.04 ± 21.62
    61.46 ± 18.07
        Tisotumab Vedotin: Cycle 2
    ±
    76.69 ± 9.53
    69.74 ± 7.99
    62.61 ± 6.03
    99.20 ± 20.82
    70.21 ± 42.93
    74.82 ± 4.19
    72.74 ± 5.79
        Total HuMax-TF: Cycle 1
    ±
    51.55 ± 1.61
    60.27 ± 17.79
    57.38 ± 8.65
    77.55 ± 10.74
    67.26 ± 50.61
    68.69 ± 30.52
    50.69 ± 7.20
        Total HuMax-TF: Cycle 2
    ±
    55.75 ± 10.80
    57.13 ± 8.90
    58.48 ± 12.66
    84.98 ± 22.85
    50.62 ± 36.02
    60.40 ± 17.48
    58.10 ± 12.31
    Notes
    [8] - Not calculated where the percentage of the AUC that is due to the extrapolation is more than 20%.
    [9] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 1 N = 2 Total HuMax-TF Cycle 2 N = 2
    [10] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 2 N = 2
    [11] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 2 N = 2
    [12] - Tisotumab Vedotin Cycle 2 N = 3 Total HuMax-TF Cycle 2 N = 3
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Area Under the Curve from Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF

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    End point title
    Dose Escalation and Expansion Part: Area Under the Curve from Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3 [13]
    6 [14]
    168 [15]
    Units: day*ug/mL
    geometric mean (geometric coefficient of variation)
        Tisotumab Vedotin: Cycle 1
    2.5 ± 3.1
    15.4 ± 8.2
    25.1 ± 16.9
    45.2 ± 9.3
    33.1 ± 19.0
    63.0 ± 49.3
    52.3 ± 33.1
    84.9 ± 33.7
    79.31 ± 49.40
        Tisotumab Vedotin: Cycle 2
    2.0 ± 15.7
    9.9 ± 49.1
    25.6 ± 7.1
    45.2 ± 10.1
    29.8 ± 25.1
    42.7 ± 72.7
    62.7 ± 21.5
    86.3 ± 14.4
    68.54 ± 55.49
        Total HuMax-TF: Cycle 1
    2.9 ± 0.5
    15.4 ± 53.1
    35.0 ± 18.9
    60.4 ± 13.4
    44.9 ± 27.8
    86.7 ± 54.3
    85.9 ± 36.7
    123.0 ± 34.7
    112.70 ± 45.23
        Total HuMax-TF: Cycle 2
    2.4 ± 12.3
    14.4 ± 55.4
    35.7 ± 7.1
    58.8 ± 15.5
    40.9 ± 26.2
    60.2 ± 76.6
    92.5 ± 33.4
    133.6 ± 13.9
    114.54 ± 45.83
    Notes
    [13] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 2 N = 2
    [14] - Tisotumab Vedotin Cycle 2 N = 3 Total HuMax-TF Cycle 2 N = 3
    [15] - Tisotumab Vedotin Cycle 1 N = 167 Tisotumab Vedotin Cycle 2 N = 146 HuMax-TF Cycle 2 N = 146
    No statistical analyses for this end point

    Secondary: Dose Escalation Part: Area Under the Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF

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    End point title
    Dose Escalation Part: Area Under the Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. AUC0-inf was only analyzed in the dose escalation part of the study. Data was not planned to be collected for the AUC0-inf of tisotumab vedotin and total HuMax-TF for the dose expansion part. 99999 = no evaluable data. 99999 is presented when no participants had evaluable data or only 1 participant had evaluable data, so geometric coefficient of variation could not be calculated.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Number of subjects analysed
    0 [16]
    3 [17]
    3
    3
    3
    3 [18]
    3 [19]
    5 [20]
    Units: day*ug/mL
    geometric mean (geometric coefficient of variation)
        Tisotumab Vedotin: Cycle 1
    ±
    15.57 ± 7.81
    25.77 ± 15.70
    46.68 ± 10.99
    33.95 ± 20.93
    63.88 ± 48.61
    53.47 ± 30.88
    105.84 ± 8.68
        Tisotumab Vedotin: Cycle 2
    ±
    14.52 ± 4.98
    26.12 ± 6.44
    46.59 ± 9.98
    30.56 ± 26.43
    80.59 ± 24.03
    64.10 ± 19.06
    88.95 ± 11.04
        Total HuMax-TF: Cycle 1
    ±
    23.75 ± 0.20
    37.02 ± 16.39
    69.96 ± 13.26
    48.19 ± 35.67
    90.08 ± 52.74
    93.29 ± 30.45
    157.81 ± 12.70
        Total HuMax-TF: Cycle 2
    ±
    23.01 ± 9.95
    37.08 ± 6.37
    67.93 ± 14.25
    43.41 ± 30.31
    136.08 ± 12.41
    98.59 ± 26.45
    145.82 ± 9.42
    Notes
    [16] - Not calculated where the percentage of the AUC that is due to the extrapolation is more than 20%.
    [17] - Total HuMax-TF Cycle 1 N = 2 Total HuMax-TF Cycle 2 N = 2
    [18] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 2 N = 2
    [19] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 2 N = 2
    [20] - Tisotumab Vedotin Cycle 2 N = 3 Total HuMax-TF Cycle 1 N = 2 Total HuMax-TF Cycle 2 N = 3
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF

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    End point title
    Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3 [21]
    6 [22]
    168 [23]
    Units: ug/mL
    geometric mean (geometric coefficient of variation)
        Tisotumab Vedotin: Cycle 1
    4.78 ± 12.35
    12.20 ± 9.47
    19.81 ± 17.32
    34.67 ± 18.48
    23.12 ± 21.10
    35.42 ± 39.20
    32.30 ± 22.08
    55.53 ± 10.31
    29.1 ± 34.1
        Tisotumab Vedotin: Cycle 2
    3.85 ± 27.65
    12.51 ± 11.51
    20.25 ± 5.14
    32.38 ± 7.11
    21.84 ± 24.97
    35.92 ± 30.39
    44.30 ± 0.32
    48.79 ± 26.37
    26.1 ± 41.2
        Total HuMax-TF: Cycle 1
    4.90 ± 13.00
    11.84 ± 8.31
    17.98 ± 11.64
    29.30 ± 10.14
    23.55 ± 25.16
    30.57 ± 37.42
    38.78 ± 21.77
    58.02 ± 12.77
    39.8 ± 31.1
        Total HuMax-TF: Cycle 2
    3.96 ± 21.83
    11.54 ± 8.83
    16.90 ± 1.57
    31.33 ± 8.13
    22.11 ± 21.03
    37.71 ± 42.96
    43.40 ± 6.67
    53.67 ± 19.75
    38.3 ± 33.3
    Notes
    [21] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 2 N = 2
    [22] - Tisotumab Vedotin Cycle 2 N = 3 Total HuMax-TF Cycle 2 N = 3
    [23] - Tisotumab Vedotin Cycle 1 N = 167 Tisotumab Vedotin Cycle 1 N = 146 Total HuMax-TF Cycle 2 N = 146
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF

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    End point title
    Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3 [24]
    6 [25]
    168 [26]
    Units: hours
    geometric mean (geometric coefficient of variation)
        Tisotumab Vedotin: Cycle 1
    1.47 ± 72.74
    1.18 ± 13.03
    1.34 ± 11.77
    1.15 ± 11.66
    1.12 ± 9.55
    1.18 ± 14.30
    1.18 ± 7.45
    1.11 ± 12.52
    1.21 ± 364.12
        Tisotumab Vedotin: Cycle 2
    1.54 ± 63.29
    1.34 ± 6.27
    1.32 ± 5.96
    1.13 ± 11.18
    1.21 ± 16.61
    2.44 ± 35.75
    1.14 ± 9.29
    1.29 ± 7.55
    1.44 ± 303.89
        Total HuMax-TF: Cycle 1
    2.20 ± 49.15
    1.18 ± 13.03
    1.34 ± 11.77
    1.15 ± 11.66
    1.12 ± 9.55
    1.18 ± 14.30
    1.18 ± 7.45
    1.11 ± 12.52
    1.10 ± 397.92
        Total HuMax-TF: Cycle 2
    2.19 ± 46.56
    1.34 ± 6.27
    1.32 ± 5.96
    1.13 ± 11.18
    1.21 ± 16.61
    1.76 ± 50.43
    1.14 ± 9.29
    1.29 ± 7.55
    1.15 ± 356.23
    Notes
    [24] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 2 N = 2
    [25] - Tisotumab Vedotin Cycle 2 N = 3 Total HuMax-TF Cycle 2 N = 3
    [26] - Tisotumab Vedotin Cycle 1 N = 167 Tisotumab Vedotin Cycle 2 N = 146 Total HuMax-TF Cycle 2 = 146
    No statistical analyses for this end point

    Secondary: Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF

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    End point title
    Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. T1/2 was determined only for the dose escalation part of the study. Data was not planned to be collected for t1/2 of tisotumab vedotin and total HuMax-TF for the dose expansion part per the study protocol.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3 [27]
    6 [28]
    Units: hours
    geometric mean (geometric coefficient of variation)
        Tisotumab Vedotin: Cycle 1
    12.22 ± 11.61
    29.53 ± 4.08
    33.72 ± 6.26
    41.06 ± 6.85
    32.42 ± 20.05
    47.89 ± 25.82
    40.93 ± 11.48
    41.19 ± 34.02
        Tisotumab Vedotin: Cycle 2
    13.54 ± 5.50
    23.50 ± 39.89
    33.68 ± 1.74
    40.44 ± 4.69
    33.62 ± 14.50
    32.15 ± 62.74
    39.89 ± 23.15
    48.93 ± 5.61
        Total HuMax-TF: Cycle 1
    16.05 ± 27.93
    28.66 ± 30.64
    42.52 ± 7.48
    57.37 ± 8.65
    42.72 ± 34.62
    57.72 ± 17.47
    54.95 ± 5.32
    55.10 ± 27.36
        Total HuMax-TF: Cycle 2
    18.34 ± 8.73
    30.71 ± 27.65
    40.37 ± 4.27
    56.77 ± 9.60
    42.18 ± 25.39
    46.24 ± 53.11
    51.06 ± 9.18
    66.05 ± 10.07
    Notes
    [27] - Tisotumab Vedotin Cycle 2 N = 2 Total HuMax-TF Cycle 2 N = 2
    [28] - Tisotumab Vedotin Cycle 2 N = 3 Total HuMax-TF Cycle 2 N = 3
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE)

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    End point title
    Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE)
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3 [29]
    6 [30]
    168 [31]
    Units: day*ng/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1
    6.20 ± 72.05
    12.61 ± 28.18
    12.22 ± 67.23
    11.63 ± 52.69
    26.55 ± 44.24
    22.55 ± 57.26
    67.42 ± 59.98
    26.47 ± 59.35
    25.80 ± 93.91
        Cycle 2
    3.19 ± 140.85
    4.69 ± 87.27
    14.89 ± 66.97
    16.92 ± 58.12
    21.51 ± 34.25
    18.97 ± 52.14
    36.20 ± 33.82
    37.50 ± 43.08
    23.48 ± 76.47
    Notes
    [29] - Cycle 2 N = 2
    [30] - Cycle 2 N = 3
    [31] - Cycle 2 N = 145
    No statistical analyses for this end point

    Secondary: Dose Escalation Part: AUC0-inf of Free MMAE

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    End point title
    Dose Escalation Part: AUC0-inf of Free MMAE
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. AUC0-inf was not planned to be collected for the dose expansion part. AUC0-inf is not calculated where the percentage of the AUC that is due to the extrapolation is more than 20%. 99999 = no evaluable data. 99999 is presented when no participants had evaluable data or only 1 participant had evaluable data, so geometric coefficient of variation could not be calculated.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Number of subjects analysed
    2 [32]
    1 [33]
    2
    1
    2 [34]
    1
    1 [35]
    1
    Units: day*ng/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1
    12.63 ± 12.44
    13.93 ± 99999
    16.32 ± 57.56
    20.39 ± 0
    27.08 ± 58.96
    25.29 ± 99999
    78.31 ± 99999
    63.03 ± 99999
        Cycle 2
    99999 ± 99999
    99999 ± 99999
    22.32 ± 43.62
    31.40 ± 99999
    31.43 ± 99999
    33.23 ± 99999
    99999 ± 99999
    58.95 ± 99999
    Notes
    [32] - Cycle 2 N = 0
    [33] - Cycle 2 N = 0
    [34] - Cycle 2 N = 1
    [35] - Cycle 2 N = 0
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Cmax of Free MMAE

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    End point title
    Dose Escalation and Expansion Part: Cmax of Free MMAE
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3 [36]
    6 [37]
    168 [38]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1
    0.760 ± 62.505
    1.673 ± 30.756
    1.524 ± 54.491
    1.410 ± 19.149
    2.807 ± 39.398
    2.587 ± 29.172
    6.351 ± 61.505
    4.877 ± 31.350
    3.16 ± 88.30
        Cycle 2
    1.091 ± 74.293
    1.342 ± 24.320
    2.059 ± 51.470
    2.243 ± 50.367
    2.718 ± 39.492
    2.035 ± 39.785
    3.369 ± 36.875
    4.704 ± 18.856
    2.73 ± 78.69
    Notes
    [36] - Cycle 2 N = 2
    [37] - Cycle 2 N = 3
    [38] - Cycle 2 N = 145
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Tmax of Free MMAE

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    End point title
    Dose Escalation and Expansion Part: Tmax of Free MMAE
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    End point type
    Secondary
    End point timeframe
    Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3 [39]
    6 [40]
    168 [41]
    Units: hours
    geometric mean (geometric coefficient of variation)
        Cycle 1
    23.88 ± 4.41
    22.77 ± 16.56
    24.39 ± 7.72
    24.19 ± 5.52
    25.07 ± 0.68
    47.74 ± 114.28
    83.24 ± 67.57
    84.88 ± 61.54
    154.28 ± 54.214
        Cycle 2
    23.73 ± 5.78
    24.05 ± 8.48
    23.92 ± 13.04
    24.94 ± 1.48
    25.26 ± 0.76
    46.24 ± 112.48
    65.15 ± 104.61
    47.12 ± 112.10
    125.38 ± 31.21
    Notes
    [39] - Cycle 2 N = 2
    [40] - Cycle 2 N = 3
    [41] - Cycle 2 = 145
    No statistical analyses for this end point

    Secondary: Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE

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    End point title
    Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE
    End point description
    PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. T1/2 was determined only for the dose escalation part of the study.
    End point type
    Secondary
    End point timeframe
    Dose escalation part (Cycles 1 and 2): Screening, pre-dose Day 1 then 0.25, 2, 5, 12, 24, 168, 336 and 504 hours post-dose.
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Number of subjects analysed
    2 [42]
    1 [43]
    2
    1
    2 [44]
    1
    1 [45]
    1
    Units: hours
    geometric mean (geometric coefficient of variation)
        Cycle 1
    95.15 ± 25.74
    69.34 ± 99999
    63.98 ± 2.24
    62.58 ± 99999
    63.65 ± 7.86
    78.90 ± 99999
    57.74 ± 99999
    68.47 ± 99999
        Cycle 2
    99999 ± 99999
    99999 ± 99999
    69.65 ± 3.86
    60.71 ± 99999
    70.20 ± 99999
    78.94 ± 99999
    99999 ± 99999
    63.92 ± 99999
    Notes
    [42] - Cycle 2 N = 0
    [43] - Cycle 2 N = 0
    [44] - Cycle 2 N = 1
    [45] - Cycle 2 N = 0
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Number of Participants with Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin

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    End point title
    Dose Escalation and Expansion Part: Number of Participants with Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin
    End point description
    Participants who met the criterion for positive ADAs on treatment were defined as participants who were negative at baseline and had at least one positive post-baseline result, or participants who were positive at baseline and had at least one post-baseline result with a titer higher than baseline.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    3
    12
    49
    12
    13
    12
    33
    18
    Units: Participants
    0
    0
    0
    0
    0
    0
    0
    0
    1
    3
    0
    0
    1
    0
    1
    No statistical analyses for this end point

    Secondary: Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage

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    End point title
    Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    Units: participants
    0
    0
    0
    1
    0
    2
    1
    3
    No statistical analyses for this end point

    Secondary: Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction in the Sum of Lesion Measurements

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    End point title
    Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction in the Sum of Lesion Measurements
    End point description
    The number of subjects analysed includes all participants with baseline and one post-baseline evaluable tumor assessment.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    14
    50
    12
    11
    14
    33
    12
    Units: millimeter(s)
        median (full range (min-max))
    6.00 (-127.0 to 41.0)
    -8.50 (-64.0 to 50.0)
    1.00 (-11.0 to 26.0)
    -2.00 (-51.0 to 40.0)
    0.00 (-59.0 to 31.0)
    -4.00 (-41.0 to 115.0)
    -1.00 (-11.0 to 15.0)
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Percentage Change from Baseline in Prostate Specific Antigen (PSA)

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    End point title
    Dose Escalation and Expansion Part: Percentage Change from Baseline in Prostate Specific Antigen (PSA)
    End point description
    PSA was only assessed in participants with castrate-resistant prostate cancer. 99999 = no evaluable data. 99999 is presented when no participants had evaluable data or only 1 participant had evaluable data, so geometric coefficient of variation could not be calculated. The 'number of subjects analysed' number includes all participants with baseline and end of study evaluable assessment.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    0 [46]
    1
    0 [47]
    1
    1
    0 [48]
    0 [49]
    0 [50]
    11
    Units: percentage change in PSA
        median (full range (min-max))
    ( to )
    64.35 (64.35 to 64.35)
    ( to )
    40.91 (40.91 to 40.91)
    3.92 (3.92 to 3.92)
    ( to )
    ( to )
    ( to )
    60.07 (3.4 to 996.5)
    Notes
    [46] - No participants with castrate-resistant prostate cancer
    [47] - No participants with castrate-resistant prostate cancer
    [48] - No participants with castrate-resistant prostate cancer
    [49] - No participants with castrate-resistant prostate cancer
    [50] - No participants with castrate-resistant prostate cancer
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Part: Percentage Change from Baseline in CA-125

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    End point title
    Dose Escalation and Expansion Part: Percentage Change from Baseline in CA-125
    End point description
    In the dose escalation part, CA-125 was only assessed for participants with ovarian cancer. In the dose expansion part, CA-125 was intended to be assessed only for participants with ovarian and endometrium cancer, but was additionally assessed for some participants with NSCLC and cervical cancer. 99999 = no evaluable data. 99999 is presented when no participants had evaluable data or only 1 participant had evaluable data, so geometric coefficient of variation could not be calculated. The 'number of subjects analysed' number includes all participants with baseline and end of study evaluable assessment.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer
    Number of subjects analysed
    0 [51]
    0 [52]
    0 [53]
    1
    0 [54]
    1
    1
    2
    8
    10
    3
    25
    Units: percentage change
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    18.75 (18.75 to 18.75)
    ( to )
    -13.98 (-13.98 to -13.98)
    113.71 (113.71 to 113.71)
    11.62 (-22.7 to 45.9)
    -25.17 (-88.7 to 240.5)
    37.85 (-46.1 to 666.2)
    180.94 (47.1 to 980.5)
    73.19 (-89.0 to 1924.4)
    Notes
    [51] - No participants with ovarian cancer
    [52] - No participants with ovarian cancer
    [53] - No participants with ovarian cancer
    [54] - No participants with ovarian cancer
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Parts: Objective Response Rate

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    End point title
    Dose Escalation and Expansion Parts: Objective Response Rate
    End point description
    Percentage of participants with either a best overall response of complete response (CR) or partial response (PR) as assessed by the investigator per RECIST v1.1. The best overall response is the best response recorded from the start of the treatment until disease progression.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    15
    55
    14
    15
    15
    36
    18
    Units: Percentage of participants
        number (confidence interval 95%)
    0 (0 to 71)
    0 (0 to 71)
    0 (0 to 71)
    33 (1 to 91)
    0 (0 to 71)
    0 (0 to 71)
    0 (0 to 71)
    0 (0 to 71)
    27 (8 to 55)
    24 (13 to 37)
    7 (0 to 34)
    13 (2 to 40)
    13 (2 to 40)
    14 (5 to 29)
    0 (0 to 19)
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Parts: Disease Control Rate

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    End point title
    Dose Escalation and Expansion Parts: Disease Control Rate
    End point description
    Disease control rate was defined as the percentage of participants with CR, PR or SD as per investigator assessment per RECIST version 1.1 after 6, 12, 24 and 36 weeks.
    End point type
    Secondary
    End point timeframe
    At 6, 12, 24 and 36 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    15
    55
    14
    15
    15
    36
    18
    Units: Percentage of participants
    number (confidence interval 95%)
        Week 6
    0 (0 to 71)
    33 (1 to 91)
    33 (1 to 91)
    67 (9 to 99)
    33 (1 to 91)
    100 (29 to 100)
    67 (9 to 99)
    50 (12 to 88)
    47 (21 to 73)
    60 (46 to 73)
    64 (35 to 87)
    40 (16 to 68)
    60 (32 to 84)
    72 (55 to 86)
    61 (36 to 83)
        Week 12
    0 (0 to 71)
    33 (1 to 91)
    33 (1 to 91)
    67 (9 to 99)
    0 (0 to 71)
    67 (9 to 99)
    33 (1 to 91)
    0 (0 to 46)
    33 (12 to 62)
    47 (34 to 61)
    43 (18 to 71)
    20 (4 to 48)
    13 (2 to 40)
    42 (26 to 59)
    28 (10 to 53)
        Week 24
    0 (0 to 71)
    33 (1 to 91)
    0 (0 to 71)
    33 (1 to 91)
    0 (0 to 71)
    0 (0 to 71)
    0 (0 to 71)
    0 (0 to 46)
    20 (4 to 48)
    18 (9 to 31)
    21 (5 to 51)
    7 (0 to 32)
    13 (2 to 40)
    14 (5 to 29)
    6 (0 to 27)
        Week 36
    0 (0 to 71)
    33 (1 to 91)
    0 (0 to 71)
    33 (1 to 91)
    0 (0 to 71)
    0 (0 to 71)
    0 (0 to 71)
    0 (0 to 46)
    7 (0 to 32)
    11 (4 to 22)
    0 (0 to 23)
    0 (0 to 22)
    7 (0 to 32)
    3 (0 to 15)
    6 (0 to 27)
    No statistical analyses for this end point

    Secondary: Dose Escalation and Expansion Parts: Progression Free Survival (PFS)

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    End point title
    Dose Escalation and Expansion Parts: Progression Free Survival (PFS)
    End point description
    PFS was defined as the median time in weeks from Day 1 in Cycle 1 to first disease progression or death as assessed by the investigator. Only deaths that occurred within 60 days of the last visit were considered in the analysis and result are presented based on Kaplan-Meier estimates. Any results that could not be estimated are indicated as 99999.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    3
    3
    3
    3
    3
    3
    3
    6
    15
    55
    14
    15
    15
    36
    18
    Units: weeks
        median (confidence interval 95%)
    5.1 (4.9 to 5.4)
    6.0 (3.9 to 49.1)
    6.1 (4.9 to 99999)
    27.1 (6.0 to 99999)
    6.1 (5.3 to 10.4)
    17.1 (11.3 to 99999)
    12.3 (5.0 to 14.1)
    11.3 (2.1 to 11.3)
    11.0 (5.1 to 43.0)
    18.1 (9.3 to 23.0)
    99999 (5.1 to 99999)
    10.1 (5.3 to 17.0)
    13.0 (5.1 to 17.3)
    13.0 (12.1 to 18.3)
    12.9 (7.1 to 23.7)
    No statistical analyses for this end point

    Secondary: Dose Expansion Parts: Duration of Response (DOR)

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    End point title
    Dose Expansion Parts: Duration of Response (DOR)
    End point description
    DOR was defined as the median time in weeks from when confirmed response was first documented until the first documented disease progression, or death from any cause, whichever was earliest as assessed by the investigator. A responder was defined as any participant with a best overall response of confirmed CR or PR. The 'subjects analysed' number only includes participants considered a responder. Any results in the dose expansion part of the study that could not be estimated are indicated as 99999. The duration of response could not be estimated for the dose escalation part of the study as all participants who responded did not have disease progression or died due to any cause.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of follow-up, up to a maximum of 60 weeks
    End point values
    Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Number of subjects analysed
    4
    13
    1
    2
    2
    5
    0 [55]
    Units: weeks
        median (confidence interval 95%)
    32.0 (11.0 to 32.0)
    18.4 (13.1 to 41.7)
    99999 (99999 to 99999)
    18.3 (11.6 to 25.0)
    99999 (12.0 to 99999)
    21.4 (13.1 to 29.6)
    ( to )
    Notes
    [55] - No participants with confirmed CR or PR.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The exposure ranged from 1 to 249 days in the escalation part and from 1 to 325 days in the expansion part.
    Adverse event reporting additional description
    Deaths from all causes are reported from day of enrollment to end of follow up (up to maximum of 60 weeks).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Dose Escalation Part: 0.3 mg/kg
    Reporting group description
    -

    Reporting group title
    Dose Escalation Part: 0.6 mg/kg
    Reporting group description
    -

    Reporting group title
    Dose Escalation Part: 0.9 mg/kg
    Reporting group description
    -

    Reporting group title
    Dose Escalation Part: 1.2 mg/kg
    Reporting group description
    -

    Reporting group title
    Dose Escalation Part: 1.5 mg/kg
    Reporting group description
    -

    Reporting group title
    Dose Escalation Part: 1.8 mg/kg
    Reporting group description
    -

    Reporting group title
    Dose Escalation Part: 2.0 mg/kg
    Reporting group description
    -

    Reporting group title
    Dose Escalation Part: 2.2 mg/kg
    Reporting group description
    -

    Reporting group title
    Dose Expansion Part: Bladder Cancer
    Reporting group description
    -

    Reporting group title
    Dose Expansion Part: Cervical Cancer
    Reporting group description
    -

    Reporting group title
    Dose Expansion Part: Endometrial Cancer
    Reporting group description
    -

    Reporting group title
    Dose Expansion Part: Esophageal Cancer
    Reporting group description
    -

    Reporting group title
    Dose Expansion Part: Non-Small-Cell Lung Cancer
    Reporting group description
    -

    Reporting group title
    Dose Expansion Part: Ovarian Cancer
    Reporting group description
    -

    Reporting group title
    Dose Expansion Part: Prostate Cancer
    Reporting group description
    -

    Serious adverse events
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small-Cell Lung Cancer Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 3 (66.67%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    4 / 6 (66.67%)
    7 / 15 (46.67%)
    26 / 55 (47.27%)
    5 / 14 (35.71%)
    8 / 15 (53.33%)
    6 / 15 (40.00%)
    13 / 36 (36.11%)
    6 / 18 (33.33%)
         number of deaths (all causes)
    2
    1
    0
    0
    0
    0
    0
    0
    0
    2
    0
    1
    1
    2
    1
         number of deaths resulting from adverse events
    2
    1
    0
    0
    0
    0
    0
    0
    0
    2
    0
    1
    0
    1
    0
    Vascular disorders
    Vascular disorders
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression
         subjects affected / exposed
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal cancer metastatic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 15 (6.67%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Malaise
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    2 / 36 (5.56%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Catheter site pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Insomnia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Female genital tract fistula
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Stress fracture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngeal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Guillain-barre syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Hypoacusis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    4 / 55 (7.27%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    2 / 36 (5.56%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 15 (0.00%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    2 / 36 (5.56%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    2 / 36 (5.56%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 15 (6.67%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal ulcer haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal perforation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    2 / 18 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Stent malfunction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 15 (6.67%)
    0 / 36 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 15 (6.67%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    2 / 36 (5.56%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conjunctivitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 15 (6.67%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    1 / 36 (2.78%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Micrococcus infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 15 (6.67%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 15 (6.67%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis escherichia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Klebsiella infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    0 / 36 (0.00%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small-Cell Lung Cancer Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    6 / 6 (100.00%)
    15 / 15 (100.00%)
    55 / 55 (100.00%)
    14 / 14 (100.00%)
    15 / 15 (100.00%)
    15 / 15 (100.00%)
    36 / 36 (100.00%)
    18 / 18 (100.00%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 15 (0.00%)
    5 / 36 (13.89%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    6
    0
    Hypotension
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)