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    Clinical Trial Results:
    A First-in-human Dose-escalation and Dose-finding Phase 1 Trial of IMAB027 in Patients with Recurrent Advanced Ovarian Cancer

    Summary
    EudraCT number
    		 2013-002755-15
    Trial protocol
    		 BE  
    Global end of trial date
    28 Oct 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Mar 2019
    First version publication date
    14 Mar 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GM-IMAB-002-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02054351
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Protocol Number: 1650-CL-0101, Acronym: OVAR
    Sponsors
    Sponsor organisation name
    Astellas Pharma Global Development US
    Sponsor organisation address
    1 Astellas Way, Northbrook, IL, United States, 60062
    Public contact
    Clinical Trial Disclosure, Astellas Pharma Global Development US, astellas.resultsdisclosure@astellas.com
    Scientific contact
    Clinical Trial Disclosure, Astellas Pharma Global Development US, astellas.resultsdisclosure@astellas.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
    28 Oct 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Oct 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of this study were to assess the safety and tolerability of ASP1650 at each dose tested and to define the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT).
    Protection of trial subjects
    This clinical study was written, conducted and reported in accordance with the protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Feb 2014
    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
    Belgium: 17
    Country: Number of subjects enrolled
    Germany: 25
    Worldwide total number of subjects
    42
    EEA total number of subjects
    42
    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)
    21
    From 65 to 84 years
    21
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was an all female study, for participants with recurrent advanced ovarian cancer.

    Pre-assignment
    Screening details
    		 Eligible participants who met inclusion criteria and none of the exclusion criteria were enrolled. A total of 43 female participants were enrolled in Stages 1 and 2 of the study. One participant that enrolled in Stage 2, was a screen failure due to an adverse event (AE) experienced before being assigned to a dosing cohort.

    Period 1
    Period 1 title
    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
    		 ASP1650 Stage 1/2 1-1000 mg/m^2
    Arm description
    		 Stage 1 participants received weekly intrasubject dose escalation of 1 mg/m^2, 10 mg/m^2, 30 mg/m^2 and 100 mg/m^2 ASP1650. Stage 2 participants received 100 mg/m^2, 300 mg/m^2, 600 mg/m^2 or 1000 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants in lower doses may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ASP1650
    Investigational medicinal product code
    Other name
    IMAB027
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    ASP1650 was given as a 2 hour intravenous (IV) infusion.

    Arm title
    		 ASP1650 Stage 2 – 100 mg/m^2
    Arm description
    		 Participants received 100 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ASP1650
    Investigational medicinal product code
    Other name
    IMAB027
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    ASP1650 was given as a 2 hour intravenous (IV) infusion.

    Arm title
    		 ASP1650 Stage 2 – 300 mg/m^2
    Arm description
    		 Participants received 300 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ASP1650
    Investigational medicinal product code
    Other name
    IMAB027
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    ASP1650 was given as a 2 hour intravenous (IV) infusion.

    Arm title
    		 ASP1650 Stage 2 – 600 mg/m^2
    Arm description
    		 Participants received 600 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ASP1650
    Investigational medicinal product code
    Other name
    IMAB027
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    ASP1650 was given as a 2 hour intravenous (IV) infusion.

    Arm title
    		 ASP1650 Stage 2 – 1000 mg/m^2
    Arm description
    		 Participants received 1000 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ASP1650
    Investigational medicinal product code
    Other name
    IMAB027
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    ASP1650 was given as a 2 hour intravenous (IV) infusion.

    Number of subjects in period 1
    		ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Started
    3
    10
    10
    10
    9
    Treated
    3
    10
    10
    10
    9
    Escalated to 1000 mg/m^2
    0
    5
    3
    2
    0
    Completed
    0
    0
    0
    0
    0
    Not completed
    3
    10
    10
    10
    9
         Progressive Disease (PD) per RECIST
    -
    7
    5
    6
    3
         Death
    -
    -
    1
    -
    2
         Miscellaneous
    -
    -
    -
    1
    -
         Symptomatic Deterioration
    -
    2
    4
    1
    1
         Withdrawal of Consent Without Follow-Up
    -
    -
    -
    1
    -
         Missing
    2
    1
    -
    1
    3
         Withdrawal of Consent With Follow-Up
    1
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ASP1650 Stage 1/2 1-1000 mg/m^2
    Reporting group description
    		 Stage 1 participants received weekly intrasubject dose escalation of 1 mg/m^2, 10 mg/m^2, 30 mg/m^2 and 100 mg/m^2 ASP1650. Stage 2 participants received 100 mg/m^2, 300 mg/m^2, 600 mg/m^2 or 1000 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants in lower doses may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 100 mg/m^2
    Reporting group description
    		 Participants received 100 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 300 mg/m^2
    Reporting group description
    		 Participants received 300 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 600 mg/m^2
    Reporting group description
    		 Participants received 600 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 1000 mg/m^2
    Reporting group description
    		 Participants received 1000 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent.

    Reporting group values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2 Total
    Number of subjects
    		 3 10 10 10 9
    Age categorical
    Units: Subjects
    Age continuous
    The analysis population for baseline characteristics consisted of the safety analysis set (SAF), the safety population was comprised of all participants who received at least 1 dose of study drug.
    Units: years
        arithmetic mean (standard deviation)
    		 61.3 ± 5.69 67.9 ± 8.33 63.9 ± 6.82 65.8 ± 8.35 66.9 ± 8.85 -
    Gender categorical
    Units:
        Male
    		 0 0 0 0 0 0
        Female
    		 3 10 10 10 9 42
    Race
    Units: Subjects
        Black or African American
    		 0 1 1 0 0 2
        White
    		 3 9 9 10 9 40

    End points

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    End points reporting groups
    Reporting group title
    ASP1650 Stage 1/2 1-1000 mg/m^2
    Reporting group description
    		 Stage 1 participants received weekly intrasubject dose escalation of 1 mg/m^2, 10 mg/m^2, 30 mg/m^2 and 100 mg/m^2 ASP1650. Stage 2 participants received 100 mg/m^2, 300 mg/m^2, 600 mg/m^2 or 1000 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants in lower doses may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 100 mg/m^2
    Reporting group description
    		 Participants received 100 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 300 mg/m^2
    Reporting group description
    		 Participants received 300 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 600 mg/m^2
    Reporting group description
    		 Participants received 600 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 1000 mg/m^2
    Reporting group description
    		 Participants received 1000 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent.

    Subject analysis set title
    Stage 2 Participants Escalated to 1000 mg/m^2
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    At the completion of stage 2, participants who were administered <1000 m/m^2 ASP1650 received 1000 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent.

    Subject analysis set title
    Stage 1 ASP1650 1 mg/m^2
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received a single dose of ASP1650 1 mg/m^2 on Day 1.

    Subject analysis set title
    Stage 1 ASP1650 10 mg/m^2
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received a single dose of ASP1650 10 mg/m^2 on Day 8.

    Subject analysis set title
    Stage 1 ASP1650 30 mg/m^2
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received a single dose of ASP1650 30 mg/m^2 on Day 15.

    Primary: Number of Participants with Adverse Events (AEs)

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    End point title
    		 Number of Participants with Adverse Events (AEs) [1]
    End point description
    A serious adverse event (SAE) was defined as any untoward medical occurrence that: ●Resulted in death ●Was life-threatening ●Required hospitalization or prolongation of an existing hospitalization ●Resulted in disability/incapacity or ●Was a congenital anomaly/birth defect in the offspring of a study participant. A treatment-emergent adverse event (TEAE) was defined as any adverse event that occurred after the first administration of ASP1650 up to 28 days after the last dose of study drug (i.e., safety follow-up 1) or end of study, or any event that was present at baseline but worsened in severity after baseline. Severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.4.03. TEAEs of special interest were identified using specific search criteria defined by Ganymed for “inner ear disorders”, “pancreatitis” and “hypersensitivity/infusion reactions” events. The analysis population consisted of the SAF.
    End point type
    Primary
    End point timeframe
    From the first dose of study drug administration until 28 days after last dose of study drug or End of Study (EoS); Up to 13.31 months.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis is not applicable for this endpoint.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2 Stage 2 Participants Escalated to 1000 mg/m^2
    Number of subjects analysed
    3
    10
    10
    10
    9
    10
    Units: participants
        TEAEs
    3
    10
    9
    10
    9
    10
        Dose-limiting toxicity
    0
    1
    0
    0
    0
    0
        Drug-related TEAE
    3
    6
    7
    4
    8
    5
        Procedure-related TEAE
    0
    1
    1
    0
    1
    0
        Serious TEAE
    1
    5
    3
    2
    3
    3
        Drug-related serious TEAE
    1
    1
    0
    0
    0
    1
        TEAE leading to permanent discontinuation of drug
    1
    1
    2
    2
    1
    0
        TEAE leading to study drug interruption
    1
    1
    0
    1
    3
    2
        Grade 3 or higher TEAE
    3
    9
    5
    2
    5
    4
        Grade 3 or higher drug-related TEAE
    0
    1
    1
    0
    1
    2
        TEAE resulting in death
    0
    2
    1
    0
    0
    0
        TEAE of special interest
    2
    1
    2
    2
    3
    3
    No statistical analyses for this end point

    Secondary: Stage 1: Maximum Concentration (Cmax) of ASP1650

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    End point title
    		 Stage 1: Maximum Concentration (Cmax) of ASP1650
    End point description
    The analysis population consisted of the pharmacokinetic analysis set (PKAS), which was a subset of participants from the safety analysis set for whom serum concentration data were available to facilitate derivation of at least 1 pharmacokinetic (PK) parameter and for whom the time of dosing on the day of sampling was known.
    End point type
    Secondary
    End point timeframe
    Up to Day 2 after each infusion
    End point values
    		 Stage 1 ASP1650 1 mg/m^2 Stage 1 ASP1650 10 mg/m^2 Stage 1 ASP1650 30 mg/m^2
    Number of subjects analysed
    3
    3
    3
    Units: μg/mL
        arithmetic mean (standard deviation)
    0.625 ± 0.276
    6.41 ± 0.813
    22.5 ± 0.872
    No statistical analyses for this end point

    Secondary: Stage 2: Cmax of ASP1650 in Cycle 1

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    End point title
    		 Stage 2: Cmax of ASP1650 in Cycle 1 [2]
    End point description
    The analysis population consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Up to Day 21 after infusion
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint is only applicable for stage 2 arms/reporting groups.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    10
    10
    9
    8
    Units: μg/mL
        arithmetic mean (standard deviation)
    101 ± 98.4
    214 ± 99.6
    326 ± 66.1
    622 ± 126
    Statistical analysis title
    		 Statistical Assessment of Dose Proportionality
    Statistical analysis description
    Assessments were based on the power model (linear regression of natural log-transformed parameter and dose.
    Comparison groups
    ASP1650 Stage 2 – 100 mg/m^2 v ASP1650 Stage 2 – 300 mg/m^2 v ASP1650 Stage 2 – 600 mg/m^2 v ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Regression, Linear
    Parameter type
    		 Slope Estimate
    Point estimate
    0.98
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.042

    Secondary: Stage 2: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUCinf) of ASP1650 in Cycle 1

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    End point title
    		 Stage 2: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUCinf) of ASP1650 in Cycle 1 [3]
    End point description
    The analysis population consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Up to Day 21 after infusion
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint is only applicable for stage 2 arms/reporting groups.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    10
    10
    9
    8
    Units: h*mg/mL
        arithmetic mean (standard deviation)
    6.410 ± 2.210
    19.000 ± 9.940
    45.100 ± 14.700
    89.300 ± 24.000
    Statistical analysis title
    		 Statistical Assessment of Dose Proportionality
    Statistical analysis description
    Assessments were based on the power model (linear regression of natural log-transformed parameter and dose.
    Comparison groups
    ASP1650 Stage 2 – 100 mg/m^2 v ASP1650 Stage 2 – 300 mg/m^2 v ASP1650 Stage 2 – 600 mg/m^2 v ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Regression, Linear
    Parameter type
    		 Slope
    Point estimate
    1.12
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 1.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.077

    Secondary: Stage 1: Area Under the Concentration-Time Curve from Time Zero to the Last Measureable Concentration (AUClast) of ASP1650

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    End point title
    		 Stage 1: Area Under the Concentration-Time Curve from Time Zero to the Last Measureable Concentration (AUClast) of ASP1650
    End point description
    The analysis population consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Up to Day 2 after each infusion
    End point values
    		 Stage 1 ASP1650 1 mg/m^2 Stage 1 ASP1650 10 mg/m^2 Stage 1 ASP1650 30 mg/m^2
    Number of subjects analysed
    3
    3
    3
    Units: h*μg/mL
        arithmetic mean (standard deviation)
    9.87 ± 2.22
    124 ± 13.3
    433 ± 35.4
    No statistical analyses for this end point

    Secondary: Stage 2: AUClast of ASP1650 in Cycle 1

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    End point title
    		 Stage 2: AUClast of ASP1650 in Cycle 1 [4]
    End point description
    The analysis population consisted of the PKAS with available data.
    End point type
    Secondary
    End point timeframe
    Up to Day 21 after infusion
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint is only applicable for stage 2 arms/reporting groups.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    8
    8
    8
    7
    Units: h*mg/mL
        arithmetic mean (standard deviation)
    6.530 ± 1.700
    19.100 ± 8.150
    39.900 ± 10.200
    79.500 ± 17.700
    Statistical analysis title
    		 Statistical Assessment of Dose Proportionality
    Statistical analysis description
    Assessments were based on the power model (linear regression of natural log-transformed parameter and dose.
    Comparison groups
    ASP1650 Stage 2 – 100 mg/m^2 v ASP1650 Stage 2 – 300 mg/m^2 v ASP1650 Stage 2 – 600 mg/m^2 v ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects included in analysis
    31
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Regression, Linear
    Parameter type
    		 Slope
    Point estimate
    1.28
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.22
         upper limit
    		 1.34
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.035

    Secondary: Stage 2: Percentage of AUC Due to Extrapolation from the Time of the Last Measurable Concentration to Infinity (AUCinf[%extrap]) of ASP1650 in Cycle 1

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    End point title
    		 Stage 2: Percentage of AUC Due to Extrapolation from the Time of the Last Measurable Concentration to Infinity (AUCinf[%extrap]) of ASP1650 in Cycle 1 [5]
    End point description
    The analysis population consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Up to Day 21 after infusion
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint is only applicable for stage 2 arms/reporting groups.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    10
    10
    9
    8
    Units: percentage extrapolated
        arithmetic mean (standard deviation)
    9.18 ± 8.84
    9.88 ± 5.01
    14.4 ± 12.4
    14.2 ± 7.84
    No statistical analyses for this end point

    Secondary: Stage 2: Terminal Elimination Half-Life of ASP1650 (T1/2) in Cycle 1

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    End point title
    		 Stage 2: Terminal Elimination Half-Life of ASP1650 (T1/2) in Cycle 1 [6]
    End point description
    The analysis population consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Up to Day 21 after infusion
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint is only applicable for stage 2 arms/reporting groups.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    10
    10
    9
    8
    Units: hours
        median (full range (min-max))
    95.0 (76.6 to 187)
    137 (53.3 to 228)
    139 (95.5 to 261)
    153 (91.6 to 237)
    No statistical analyses for this end point

    Secondary: Stage 1: Last Measurable Concentration (Clast) of ASP1650

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    End point title
    		 Stage 1: Last Measurable Concentration (Clast) of ASP1650
    End point description
    The analysis population consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Up to Day 2 after each infusion
    End point values
    		 Stage 1 ASP1650 1 mg/m^2 Stage 1 ASP1650 10 mg/m^2 Stage 1 ASP1650 30 mg/m^2
    Number of subjects analysed
    3
    3
    3
    Units: μg/mL
        arithmetic mean (standard deviation)
    0.504 ± 0.368
    4.54 ± 0.518
    14.7 ± 2.52
    No statistical analyses for this end point

    Secondary: Stage 2: Clast of ASP1650 in Cycle 1

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    End point title
    		 Stage 2: Clast of ASP1650 in Cycle 1 [7]
    End point description
    The analysis population consisted of the PKAS with available data.
    End point type
    Secondary
    End point timeframe
    Up to Day 21 after infusion
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint is only applicable for stage 2 arms/reporting groups.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    8
    8
    8
    7
    Units: μg/mL
        arithmetic mean (standard deviation)
    2.06 ± 1.74
    9.09 ± 6.58
    21.0 ± 14.2
    44.0 ± 21.8
    No statistical analyses for this end point

    Secondary: Stage 1: Time to Maximum Concentration (Tmax) of ASP1650

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    End point title
    		 Stage 1: Time to Maximum Concentration (Tmax) of ASP1650
    End point description
    The analysis population consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Up to Day 2 after each infusion
    End point values
    		 Stage 1 ASP1650 1 mg/m^2 Stage 1 ASP1650 10 mg/m^2 Stage 1 ASP1650 30 mg/m^2
    Number of subjects analysed
    3
    3
    3
    Units: hours
        median (full range (min-max))
    1.68 (1.40 to 24.0)
    1.50 (1.03 to 3.97)
    7.95 (3.50 to 8.00)
    No statistical analyses for this end point

    Secondary: Stage 2: Tmax of ASP1650 in Cycle 1

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    End point title
    		 Stage 2: Tmax of ASP1650 in Cycle 1 [8]
    End point description
    The analysis population consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Up to Day 21 after infusion
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint is only applicable for stage 2 arms/reporting groups.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    10
    10
    9
    8
    Units: hours
        median (full range (min-max))
    2.63 (2.08 to 7.53)
    2.25 (1.05 to 8.08)
    2.50 (2.00 to 7.93)
    3.11 (2.00 to 8.50)
    No statistical analyses for this end point

    Secondary: Stage 2: Systemic Clearance (CL) of ASP1650 in Cycle 1

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    End point title
    		 Stage 2: Systemic Clearance (CL) of ASP1650 in Cycle 1 [9]
    End point description
    The analysis population consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Up to Day 21 after infusion
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint is only applicable for stage 2 arms/reporting groups.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    10
    10
    9
    8
    Units: L/h
        arithmetic mean (standard deviation)
    0.0297 ± 0.0159
    0.0362 ± 0.0175
    0.0260 ± 0.00734
    0.0207 ± 0.00439
    No statistical analyses for this end point

    Secondary: Stage 2: Volume of Distribution (Vz) of ASP1650 in Cycle 1

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    End point title
    		 Stage 2: Volume of Distribution (Vz) of ASP1650 in Cycle 1 [10]
    End point description
    The analysis population consisted of the PKAS.
    End point type
    Secondary
    End point timeframe
    Up to Day 21 after infusion
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint is only applicable for stage 2 arms/reporting groups.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    10
    10
    9
    8
    Units: Liters
        arithmetic mean (standard deviation)
    4.50 ± 1.66
    6.12 ± 2.31
    5.51 ± 0.867
    4.78 ± 1.14
    No statistical analyses for this end point

    Secondary: Number of Participants with Anti-ASP1650 Antibodies

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    End point title
    		 Number of Participants with Anti-ASP1650 Antibodies
    End point description
    The analysis population consisted of all antidrug antibody (ADA) positive participants.
    End point type
    Secondary
    End point timeframe
    Maximum duration of treatment; Up to 12.65 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    3
    10
    10
    10
    9
    Units: participants
    1
    2
    2
    1
    0
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR) according to Gynecologic Cancer Intergroup (GCIG) Criteria

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    End point title
    		 Disease Control Rate (DCR) according to Gynecologic Cancer Intergroup (GCIG) Criteria
    End point description
    DCR was defined as the fraction (percentage) of participants with complete response (CR), partial response (PR) or stable disease (SD) as best overall response according to GCIG criteria. CR was defined as disappearance of all target lesions, any pathological lymph node must have had reduction in short axis to <10 mm, disappearance of all non-target lesions & normalization of tumor marker level with no occurrence of simultaneous appearance of new lesions. PR was defined as at least 30% decrease in the sum of the longest diameter of target lesions, referencing the screening sum longest diameter, no occurrence of simultaneous increase in size of any lesion or appearance of new lesions. SD is defined in the next endpoint. The analysis population consisted of the full analysis set (FAS), which included all participants who received at least 1 dose of study drug & met the eligibility criteria.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time from first dose of study drug administration to EoS; Up to 13.31 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    2
    10
    10
    10
    9
    Units: percentage of participants
        number (confidence interval 95%)
    50.0 (1.3 to 98.7)
    10.0 (0.3 to 44.5)
    40.0 (12.2 to 73.8)
    30.0 (6.7 to 65.2)
    77.8 (40.0 to 97.2)
    No statistical analyses for this end point

    Secondary: DCR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

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    End point title
    		 DCR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
    End point description
    DCR was defined as the fraction (percentage) of participants with CR or PR or SD as best overall response according to RECIST criteria. SD was defined as neither sufficient shrinkage to qualify for PR or CR nor sufficient increase to qualify for progressive disease (PD), referencing the smallest sum longest diameter recorded since treatment started, measurements must have met the SD criteria at least once after trial entry at a minimum interval not less than 6 weeks, no occurrence of simultaneous increase in size of any lesion or appearance of new lesions, evaluable lesions must have remained stable or regressed for this category. CR and PR were defined in the previous endpoint. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time from first dose of study drug administration to EoS; Up to 13.31 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    2
    10
    10
    10
    9
    Units: percentage of participants
        number (confidence interval 95%)
    0.0 (0.0 to 0.0)
    10.0 (0.3 to 44.5)
    40.0 (12.2 to 73.8)
    30.0 (6.7 to 65.2)
    77.8 (40.0 to 97.2)
    No statistical analyses for this end point

    Secondary: DCR according to Cancer Antigen (CA)-125 Criteria

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    End point title
    		 DCR according to Cancer Antigen (CA)-125 Criteria
    End point description
    Disease control rate was defined as the fraction (percentage) of participants with complete response or partial response or stable disease as best overall response according to CA-125 criteria. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time from first dose of study drug administration to EoS; Up to 13.31 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    2
    10
    10
    10
    9
    Units: percentage of participants
        number (confidence interval 95%)
    100.0 (15.8 to 100.0)
    40.0 (12.2 to 73.8)
    80.0 (44.4 to 97.5)
    90.0 (55.5 to 99.7)
    88.9 (51.8 to 99.7)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR) according to GCIG Criteria

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    End point title
    		 Objective Response Rate (ORR) according to GCIG Criteria
    End point description
    Objective response rate comprised of the fraction (percentage) of participants with CR or PR as best overall response according to GCIG criteria. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time from first dose of study drug administration to EoS; Up to 13.31 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    2
    10
    10
    10
    9
    Units: percentage of participants
        number (confidence interval 95%)
    0.0 (0.0 to 0.0)
    0.0 (0.0 to 0.0)
    10.0 (0.3 to 44.5)
    0.0 (0.0 to 0.0)
    0.0 (0.0 to 0.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Best Overall Response According to RECIST v1.1

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    End point title
    		 Percentage of Participants with Best Overall Response According to RECIST v1.1
    End point description
    The Best Overall Response was determined as per RECIST version 1.1 criteria alone. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time from first dose of study drug administration to EoS; Up to 13.31 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    2
    10
    10
    10
    9
    Units: percentage of participants
    number (not applicable)
        CR
    0.0
    0.0
    0.0
    0.0
    0.0
        PR
    0.0
    0.0
    10.0
    0.0
    0.0
        SD
    0.0
    10.0
    30.0
    30.0
    77.8
        PD
    50.0
    70.0
    40.0
    40.0
    22.2
        Not Evaluable (NE)
    50.0
    0.0
    10.0
    0.0
    0.0
        Not Calculated (NC)
    0.0
    20.0
    10.0
    30.0
    0.0
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Best Overall Response According to CA-125

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    End point title
    		 Percentage of Participants with Best Overall Response According to CA-125
    End point description
    The Best Overall Response was determined as per CA-125 criteria alone. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time from first dose of study drug administration to EoS; Up to 13.31 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    2
    10
    10
    10
    9
    Units: percentage of participants
    number (not applicable)
        Response
    0.0
    0.0
    10.0
    0.0
    0.0
        Non-Response
    100.0
    40.0
    70.0
    90.0
    88.9
        Non-Response: Non-PR/Non-PD
    100.0
    40.0
    70.0
    90.0
    88.9
        Non-Response: Progression
    0.0
    0.0
    0.0
    0.0
    0.0
        Not Available (NA)
    0.0
    60.0
    20.0
    10.0
    11.1
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) According to GCIG criteria

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    End point title
    		 Progression Free Survival (PFS) According to GCIG criteria
    End point description
    PFS was calculated as the time in months from the date of first study drug dose administration to the earlier date between the first documented progression and the date of death by any cause. PFS was determined according to GCIG criteria. Participants who had not progressed either clinically or on the last scan, were censored as of the last tumor evaluation. PFS was analyzed using the Kaplan-Meier estimators. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time to PFS; Up to 30.62 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    2
    10
    10
    10
    9
    Units: months
        median (confidence interval 95%)
    2.8 (2.7 to 3.0)
    1.3 (0.5 to 1.5)
    1.4 (1.2 to 5.3)
    2.2 (1.2 to 3.1)
    4.2 (0.6 to 4.3)
    No statistical analyses for this end point

    Secondary: PFS According to RECIST v1.1

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    End point title
    		 PFS According to RECIST v1.1
    End point description
    PFS was calculated as the time in months from the date of first study drug dose administration to the earlier date between the first documented progression and the date of death by any cause. PFS was determined according to RECIST version 1.1 criteria alone. Participants who had not progressed either clinically or on the last scan, were censored as of the last tumor evaluation. PFS was analyzed using the Kaplan-Meier estimators. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time to PFS; Up to 9.26 months
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    2
    10
    10
    10
    9
    Units: months
        median (confidence interval 95%)
    2.8 (2.7 to 3.0)
    1.3 (0.5 to 1.5)
    1.4 (1.2 to 5.3)
    2.2 (1.2 to 3.1)
    4.2 (0.6 to 6.6)
    No statistical analyses for this end point

    Secondary: PFS According to CA-125

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    End point title
    		 PFS According to CA-125
    End point description
    PFS was calculated as the time in months from the date of first study drug dose administration to the earlier date between the first documented progression and the date of death by any cause. PFS was determined according to CA-125 criteria alone. Participants who had not progressed either clinically or on the last scan, were censored as of the last tumor evaluation. PFS was analyzed using the Kaplan-Meier estimators. The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time to PFS; Up to 30.62 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    2
    8
    7
    10
    8
    Units: months
        median (confidence interval 95%)
    11.7 (3.0 to 20.5)
    4.1 (0.7 to 10.8)
    10.2 (1.2 to 16.2)
    5.9 (3.4 to 10.0)
    6.1 (1.1 to 11.5)
    No statistical analyses for this end point

    Secondary: Ratio of Previous Relapse-Free Interval Vs. Current PFS

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    End point title
    		 Ratio of Previous Relapse-Free Interval Vs. Current PFS [11]
    End point description
    Ratio of Previous Relapse-Free Interval vs. Current PFS was defined as the ratio between Previous Relapse-Free Interval (defined as the last time period without relapse prior to study entry) and the current PFS (time in months from the date of first study drug dose to the earlier between the date of first documented progression and the date of death by any cause; calculated based on CGIC criteria). The analysis population consisted of the FAS.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time to PFS; Up to 30.62 months.
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is not applicable to the ASP1650 Stage 1/2 1-1000 mg/m2 arm/reporting group.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    9
    10
    10
    9
    Units: ratio
        arithmetic mean (standard deviation)
    6.79 ± 13.396
    18.92 ± 28.122
    12.01 ± 31.343
    6.02 ± 15.380
    No statistical analyses for this end point

    Secondary: Time to Response (TTR)

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    End point title
    		 Time to Response (TTR)
    End point description
    TTR was defined as the duration of time from start of treatment to CR or PR per GCIG criteria. The analysis population consisted of the FAS. Only one participant in the ASP1650 Stage 2 - 300 mg/m2 arm/reporting group had an overall response of CR of PR. TTR was analyzed using the Kaplan-Meier estimators. Data that was not evaluable/could not be calculated is denoted as "99999."
    End point type
    Secondary
    End point timeframe
    Maximum duration of time from first dose of study drug administration to EoS; Up to 13.31 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    0 [12]
    0 [13]
    1
    0 [14]
    0 [15]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    99999 (2.3 to 99999)
    ( to )
    ( to )
    Notes
    [12] - No participants with overall response in this arm.
    [13] - No participants with overall response in this arm.
    [14] - No participants with overall response in this arm.
    [15] - No participants with overall response in this arm.
    No statistical analyses for this end point

    Secondary: Duration of Overall Response (DOR) per RECIST v1.1

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    End point title
    		 Duration of Overall Response (DOR) per RECIST v1.1
    End point description
    Duration of overall response was calculated only for patients with Best Overall Response = CR or PR as per RECIST 1.1 alone. DOR was calculated as the time in months from the date of the first documented response (i.e., overall response = CR or PR) to the earlier between the date of the first documentation of disease progression and the date of death. The analysis population consisted of the FAS. Only one participant in the ASP1650 Stage 2 - 300 mg/m2 arm/reporting group had overall response, the only evaluable data was the median 95% CI, which was 4.6 months. DOR was analyzed using the Kaplan-Meier estimators. Due to a validation rule, ASP1650 Stage 2 - 300 mg/m^2 arm/reporting group's median of 4.6 months cannot be included in the data table and is indicated as "99999." Data that was not evaluable/could not be calculated is also denoted as "99999."
    End point type
    Secondary
    End point timeframe
    Maximum duration of time from first dose of study drug administration to EoS; Up to 13.31 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    0 [16]
    0 [17]
    1
    0 [18]
    0 [19]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    99999 (99999 to 99999)
    ( to )
    ( to )
    Notes
    [16] - No participants with overall response in this arm.
    [17] - No participants with overall response in this arm.
    [18] - No participants with overall response in this arm.
    [19] - No participants with overall response in this arm.
    No statistical analyses for this end point

    Secondary: Duration of Stable Disease (DSD) per RECIST v1.1

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    End point title
    		 Duration of Stable Disease (DSD) per RECIST v1.1
    End point description
    For participants with documented progression or death, the duration of SD was calculated as the time in months from the date of first documented SD response (i.e., overall response = CR or PR or SD) to the earlier between the date of the first documentation of disease progression and the date of death. For participants without documented progression or death (i.e., censored participants for the analysis), the duration of SD was calculated as the time in months from the date of first documented SD response (i.e., overall response = CR or PR or SD) to the date of the last overall response evaluation prior to dose level escalation to 1000 mg/m^2, if that occurred. Due to the validation rule, the ASP1650 Stage 2 - 100 mg/m^2 arm/reporting group median of 7.9 months cannot be included in the data table and is denoted as "99999." DSD was analyzed using the Kaplan-Meier estimators. Data that was not evaluable/could not be calculated is also denoted as "99999."
    End point type
    Secondary
    End point timeframe
    Maximum duration of time from first dose of study drug administration to EoS; Up to 13.31 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    0 [20]
    1
    4
    3
    7
    Units: months
        median (confidence interval 95%)
    ( to )
    99999 (99999 to 99999)
    3.5 (1.1 to 4.7)
    1.6 (1.4 to 2.8)
    2.8 (0.9 to 5.2)
    Notes
    [20] - No participants with stable disease in this arm.
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time from the date of the first study drug administration until the date of death by any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. OS was analyzed using the Kaplan-Meier estimators. The analysis population consisted of the FAS. Data that was not evaluable/could not be calculated is denoted as "99999."
    End point type
    Secondary
    End point timeframe
    Maximum duration of time to OS; Up to 33.87 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    2
    8
    7
    9
    8
    Units: months
        median (confidence interval 95%)
    11.7 (3.0 to 20.5)
    4.1 (0.7 to 10.8)
    10.2 (1.2 to 99999)
    7.4 (3.4 to 12.3)
    6.9 (1.1 to 15.2)
    No statistical analyses for this end point

    Secondary: Apparent Terminal Elimination Half-Life (T1/2) of CA-125

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    End point title
    		 Apparent Terminal Elimination Half-Life (T1/2) of CA-125
    End point description
    T½ of CA-125 was defined as the time from first study drug dose to the date half or less of the baseline CA-125 value had been reached for the first time. The analysis population consisted of the per-protocol analysis set (PPS), which included all FAS participants, excluding those for whom a major protocol deviation had been identified.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time to PFS; Up to 30.62 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    0 [21]
    0 [22]
    0 [23]
    0 [24]
    0 [25]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [21] - No participants reached half or less of baseline CA-125 in this arm.
    [22] - No participants reached half or less of baseline CA-125 in this arm.
    [23] - No participants reached half or less of baseline CA-125 in this arm.
    [24] - No participants reached half or less of baseline CA-125 in this arm.
    [25] - No participants reached half or less of baseline CA-125 in this arm.
    No statistical analyses for this end point

    Secondary: Time to Nadir of CA-125

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    End point title
    		 Time to Nadir of CA-125
    End point description
    The nadir of CA-125 was defined as the lowest value of CA-125 during the treatment period. The time to nadir of CA-125 (months) was calculated as follows: Time to nadir of CA-125 (months) = (date of nadir value of CA-125 sampling – date of first study drug dose +1)/30.4375. If the nadir occurred on several different occasions, the first in time was taken. Due to a validation rule, ASP1650 Stage 2 - 1000 mg/m^2 arm/reporting group median of 1.7 months could not be included in the data table and is denoted as "99999." Time to nadir of CA-125 was analyzed using the Kaplan-Meier estimators. The analysis population consisted of the PPS. Data that was not evaluable/could not be calculated is also denoted as "99999."
    End point type
    Secondary
    End point timeframe
    Maximum duration of time to PFS; Up to 30.62 months.
    End point values
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    0 [26]
    2
    3
    2
    1
    Units: months
        median (confidence interval 95%)
    ( to )
    1.3 (1.1 to 1.4)
    1.4 (1.4 to 1.5)
    2.3 (1.4 to 3.2)
    99999 (99999 to 99999)
    Notes
    [26] - No participants reached time to nadir of CA-125 in this arm.
    No statistical analyses for this end point

    Secondary: Time to Progression Ratio

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    End point title
    		 Time to Progression Ratio [27]
    End point description
    Time to Progression Ratio was defined as the ratio of time to progression (months) prior to dose escalation and time to progression (months) after dose escalation. The analysis population consisted of the FAS. Only Stage 2 Participants Escalated to 1000 mg/m^2 is included, however the data is shown by dose as assigned at Stage 2 entry.
    End point type
    Secondary
    End point timeframe
    Maximum duration of time from first dose of study drug administration to EoS; Up to 13.31 months.
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is not applicable to the ASP1650 Stage 1/2 1-1000 mg/m2 arm/reporting group.
    End point values
    		 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2
    Number of subjects analysed
    5
    3
    2
    0 [28]
    Units: ratio
        arithmetic mean (standard deviation)
    1.6 ± 1.05
    0.9 ± 0.61
    16.3 ± 21.68
    ±
    Notes
    [28] - No participants had time to progression ratio data.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first dose of study drug administration until 28 days after last dose of study drug or End of Study (EoS); Up to 13.31 months.
    Adverse event reporting additional description
    The total number of deaths (all causes) includes deaths reported after the time frame above.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    ASP1650 Stage 1/2 1-1000 mg/m^2
    Reporting group description
    		 Stage 1 participants received weekly intrasubject dose escalation of 1 mg/m^2, 10 mg/m^2, 30 mg/m^2 and 100 mg/m^2 ASP1650. Stage 2 participants received 100 mg/m^2, 300 mg/m^2, 600 mg/m^2 or 1000 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants in lower doses may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 100 mg/m^2
    Reporting group description
    		 Participants received 300 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 300 mg/m^2
    Reporting group description
    		 Participants received 300 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 600 mg/m^2
    Reporting group description
    		 Participants received 600 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent. Participants may have escalated to 1000 mg/m^2 at the discretion of the investigator and if deemed to be beneficial for the participant.

    Reporting group title
    ASP1650 Stage 2 – 1000 mg/m^2
    Reporting group description
    		 Participants received 1000 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent.

    Reporting group title
    Stage 2 Participants Escalated to 1000 mg/m^2
    Reporting group description
    		 At the completion of stage 2, participants who were administered <1000 m/m^2 ASP1650 received 1000 mg/m^2 ASP1650 every 3 weeks until progressive disease, toxicity or withdrawal of consent.

    Serious adverse events
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2 Stage 2 Participants Escalated to 1000 mg/m^2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    5 / 10 (50.00%)
    3 / 10 (30.00%)
    2 / 10 (20.00%)
    3 / 9 (33.33%)
    3 / 10 (30.00%)
         number of deaths (all causes)
    3
    5
    5
    8
    8
    6
         number of deaths resulting from adverse events
    0
    1
    1
    0
    0
    0
    Investigations
    Medical observation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    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
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Acute prerenal failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    Confusional state
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    General disorders and administration site conditions
    Device related infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    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
    Euthanasia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Medical device complication
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    1 / 1
    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
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Ileus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Obstruction gastric
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Hepatobiliary disorders
    Portal vein occlusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Pleuritic pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Renal and urinary disorders
    Renal failure acute
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    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
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    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
    Hyponatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 ASP1650 Stage 1/2 1-1000 mg/m^2 ASP1650 Stage 2 – 100 mg/m^2 ASP1650 Stage 2 – 300 mg/m^2 ASP1650 Stage 2 – 600 mg/m^2 ASP1650 Stage 2 – 1000 mg/m^2 Stage 2 Participants Escalated to 1000 mg/m^2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    10 / 10 (100.00%)
    8 / 10 (80.00%)
    10 / 10 (100.00%)
    9 / 9 (100.00%)
    9 / 10 (90.00%)
    Vascular disorders
    Dizziness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Haematoma
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hypertensive crisis
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Lymphoedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Skin haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Thrombophlebitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Varicose vein
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Surgical and medical procedures
    Abdominal cavity drainage
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    2
    0
    0
    1
    Cataract operation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Central venous catheterisation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Axillary pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Fatigue
         subjects affected / exposed
    0 / 3 (0.00%)
    4 / 10 (40.00%)
    3 / 10 (30.00%)
    3 / 10 (30.00%)
    6 / 9 (66.67%)
    2 / 10 (20.00%)
         occurrences all number
    0
    7
    5
    4
    13
    5
    General physical health deterioration
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    Generalised oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Local swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Localised oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Malaise
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Multi-organ failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    4 / 10 (40.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    4
    0
    1
    1
    Reproductive system and breast disorders
    Breast pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Nasopharyngitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    2
    0
    Bronchial wall thickening
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Cough
         subjects affected / exposed
    3 / 3 (100.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    3 / 9 (33.33%)
    1 / 10 (10.00%)
         occurrences all number
    5
    0
    1
    3
    4
    1
    Dysphonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    3 / 10 (30.00%)
    1 / 9 (11.11%)
    2 / 10 (20.00%)
         occurrences all number
    0
    1
    0
    4
    1
    2
    Dyspnoea exertional
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Epistaxis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Haemoptysis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Hypopnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nasal dryness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Nasal mucosal disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Obstructive airways disorder
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Pleural effusion
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    Pleuritic pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Wheezing
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Confusional state
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Depressed mood
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Sleep disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Tension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Amylase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    1
    0
    2
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 10 (20.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    1
    0
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    1
    1
    1
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Blood lactate dehydrogenase
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Blood urea increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Body temperature increased
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Breath sounds abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Electrocardiogram T wave inversion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    0
    0
    0
    1
    Haemoglobin decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Lipase increased
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
         occurrences all number
    3
    0
    3
    0
    3
    1
    Lymph node palpable
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Lymphocyte count increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Transaminases increased
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    Weight increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Transfusion reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Cardiac disorders
    Atrial flutter
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Atrioventricular block
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    3
    0
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Conduction disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    Syncope
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Disorientation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    1
    0
    3
    1
    Paresis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Somnolence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Vertigo
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 10 (20.00%)
    1 / 10 (10.00%)
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    1
    2
    0
    2
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Lymph node pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Lymphadenopathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Tympanic membrane disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Dry eye
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Eye swelling
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Abdominal pain
         subjects affected / exposed
    1 / 3 (33.33%)
    3 / 10 (30.00%)
    3 / 10 (30.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
         occurrences all number
    2
    4
    4
    0
    2
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    2
    2
    0
    Abdominal tenderness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Ascites
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 10 (20.00%)
    3 / 10 (30.00%)
    2 / 10 (20.00%)
    3 / 9 (33.33%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    4
    2
    3
    1
    Diarrhoea
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 10 (20.00%)
    4 / 10 (40.00%)
    2 / 10 (20.00%)
    4 / 9 (44.44%)
    1 / 10 (10.00%)
         occurrences all number
    1
    2
    5
    2
    6
    1
    Dry mouth
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Dysphagia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Epiploic appendagitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Faecal incontinence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Gastric ulcer
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Gastrointestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Gingival bleeding
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Ileus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Intestinal perforation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Melaena
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    4 / 10 (40.00%)
    4 / 10 (40.00%)
    4 / 9 (44.44%)
    2 / 10 (20.00%)
         occurrences all number
    0
    1
    4
    5
    5
    2
    Small intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Subileus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 10 (10.00%)
    2 / 10 (20.00%)
    3 / 10 (30.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
         occurrences all number
    1
    1
    3
    6
    2
    1
    Vomiting projectile
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Hepatobiliary disorders
    Hepatic pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    Skin and subcutaneous tissue disorders
    Night sweats
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Alopecia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    2
    1
    0
    0
    1
    0
    Decubitus ulcer
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Lividity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nail disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    2 / 10 (20.00%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    Skin burning sensation
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Xeroderma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Renal and urinary disorders
    Cystitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    4
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Dysuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Oliguria
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pollakiuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pyelocaliectasis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Renal failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Renal impairment
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 10 (30.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
         occurrences all number
    0
    4
    0
    0
    1
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    Back pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    3 / 10 (30.00%)
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    0
    1
    5
    2
    0
    2
    Groin pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    2 / 10 (20.00%)
         occurrences all number
    2
    0
    1
    0
    1
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    3
    0
    0
    1
    0
    3
    Pain in extremity
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    0
    1
    0
    0
    Infections and infestations
    Candida infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Metabolism and nutrition disorders
    Oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Decreased appetite
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    3 / 10 (30.00%)
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    2 / 10 (20.00%)
         occurrences all number
    0
    1
    3
    2
    2
    2
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
         occurrences all number
    1
    1
    1
    0
    1
    1
    Hypomagnesaemia
         subjects affected / exposed
    3 / 3 (100.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
         occurrences all number
    4
    1
    0
    2
    2
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    Metabolic disorder
         subjects affected / exposed
    2 / 3 (66.67%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Xerophthalmia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    This study was conducted by Ganymed AG, a company that was acquired by Astellas in December of 2016.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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