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    Clinical Trial Results:
    A Randomized Phase 2/3 Study of DACOGEN® (Decitabine) Plus Talacotuzumab (JNJ- 56022473; Anti CD123) Versus DACOGEN (Decitabine) Alone in Patients with AML who are not Candidates for Intensive Chemotherapy

    Summary
    EudraCT number
    		 2015-001611-12
    Trial protocol
    		 BE   ES   DE   GB   SE   PL   FR   IT  
    Global end of trial date
    25 Jan 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Feb 2019
    First version publication date
    10 Feb 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    56022473AML2002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02472145
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Janssen Research & Development, LLC
    Sponsor organisation address
    920, Route 202 South,Raritan, NJ, United States, 08869
    Public contact
    Clinical Registry group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.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
    25 Jan 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Jan 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of this trial were to assess safety and to confirm the recommended Phase 2 dose (RP2D) of talacotuzumab monotherapy (Part A) and to assess the complete response (CR) rate and overall survival (OS) in subjects with previously untreated acute myeloid leukemia (AML) who were not eligible for intense induction chemotherapy and who were randomly assigned to receive decitabine plus talacotuzumab at the RP2D or decitabine alone (Part B).
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. Safety assessment was based on reported adverse events (AE), clinical laboratory tests, vital sign measurements, physical examinations, electrocardiogram (ECG) findings, and Eastern Cooperative Oncology Group (ECOG) performance status.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Aug 2015
    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
    France: 8
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    Israel: 29
    Country: Number of subjects enrolled
    Italy: 23
    Country: Number of subjects enrolled
    Korea, Republic of: 12
    Country: Number of subjects enrolled
    Poland: 24
    Country: Number of subjects enrolled
    Russian Federation: 56
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    Turkey: 7
    Country: Number of subjects enrolled
    Taiwan: 12
    Country: Number of subjects enrolled
    United States: 26
    Country: Number of subjects enrolled
    Australia: 28
    Country: Number of subjects enrolled
    Belgium: 20
    Country: Number of subjects enrolled
    Germany: 32
    Country: Number of subjects enrolled
    Spain: 43
    Worldwide total number of subjects
    326
    EEA total number of subjects
    156
    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)
    4
    From 65 to 84 years
    305
    85 years and over
    17

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 326 subjects enrolled (10-Part A,316-Part B[159 in decitabine arm,157 in decitabine+JNJ-56022473 arm]), all subjects discontinued study. Safety: Part A- 10, Part B(Decitabine)- 165(9 who received decitabine, not JNJ-56022473 included, 3 untreated excluded),Part B(Decitabine+JNJ-56022473)-147 subjects(1 untreated,9 who received decitabine excluded).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part A: Decitabine + JNJ-56022473
    Arm description
    		 Subjects received 1 dose of JNJ-56022473 (talacotuzumab) at 9 milligram per kilogram (mg/kg) as intravenous (IV) infusion on Day 1 of cycle 1. From cycle 2 onwards, subjects received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Decitabine
    Investigational medicinal product code
    Other name
    DACOGEN
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received Decitabine at a dose of 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death.

    Investigational medicinal product name
    JNJ-56022473
    Investigational medicinal product code
    Other name
    Talacotuzumab, Anti CD123
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received 1 dose of JNJ-56022473 at 9 mg/kg as IV infusion on Day 1 of cycle 1 and on Day 8 and Day 22 of a 28-day cycle from cycle 2 onwards until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death.

    Arm title
    		 Part B: Decitabine (Alone)
    Arm description
    		 Subjects received decitabine 20 mg/m^2 on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Decitabine
    Investigational medicinal product code
    Other name
    DACOGEN
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received decitabine 20 mg/m^2 IV administered daily on Days 1 to 5 of each 28-day cycle from cycle 2 onwards until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death.

    Arm title
    		 Part B: Decitabine + JNJ-56022473
    Arm description
    		 Subjects received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Decitabine
    Investigational medicinal product code
    Other name
    DACOGEN
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received Decitabine at a dose of 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle onwards until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death.

    Investigational medicinal product name
    JNJ-56022473
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received JNJ-56022473 at 9 mg/kg as IV infusion on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death.

    Number of subjects in period 1
    		Part A: Decitabine + JNJ-56022473 Part B: Decitabine (Alone) Part B: Decitabine + JNJ-56022473
    Started
    10
    159
    157
    Treated
    10
    156
    156
    Completed
    0
    0
    0
    Not completed
    10
    159
    157
         Consent withdrawn by subject
    -
    9
    13
         Death
    10
    101
    99
         Unspecified
    -
    45
    43
         Sponsor decision
    -
    3
    2
         Lost to follow-up
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part A: Decitabine + JNJ-56022473
    Reporting group description
    		 Subjects received 1 dose of JNJ-56022473 (talacotuzumab) at 9 milligram per kilogram (mg/kg) as intravenous (IV) infusion on Day 1 of cycle 1. From cycle 2 onwards, subjects received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death.

    Reporting group title
    Part B: Decitabine (Alone)
    Reporting group description
    		 Subjects received decitabine 20 mg/m^2 on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death.

    Reporting group title
    Part B: Decitabine + JNJ-56022473
    Reporting group description
    		 Subjects received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death.

    Reporting group values
    		 Part A: Decitabine + JNJ-56022473 Part B: Decitabine (Alone) Part B: Decitabine + JNJ-56022473 Total
    Number of subjects
    		 10 159 157 326
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 4 0 0 4
        From 65 to 84 years
    		 6 148 151 305
        85 years and over
    		 0 11 6 17
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    		 65.4 ( 10.88 ) 75 ( 5.6 ) 75.2 ( 5.32 ) -
    Title for Gender
    Units: subjects
        Female
    		 4 68 77 149
        Male
    		 6 91 80 177

    End points

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    End points reporting groups
    Reporting group title
    Part A: Decitabine + JNJ-56022473
    Reporting group description
    		 Subjects received 1 dose of JNJ-56022473 (talacotuzumab) at 9 milligram per kilogram (mg/kg) as intravenous (IV) infusion on Day 1 of cycle 1. From cycle 2 onwards, subjects received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death.

    Reporting group title
    Part B: Decitabine (Alone)
    Reporting group description
    		 Subjects received decitabine 20 mg/m^2 on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death.

    Reporting group title
    Part B: Decitabine + JNJ-56022473
    Reporting group description
    		 Subjects received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death.

    Primary: Part B: Percentage of Subjects who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment

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    End point title
    		 Part B: Percentage of Subjects who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment [1]
    End point description
    Complete response rate defined as percentage of subjects who achieved complete response as per modified International Working Group (IWG) criteria. CR: Bone marrow blasts less than (<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0*10^9/liter (L) (1000/micro liter [mcL]); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions. Intent-to-Treat (ITT) population is defined as all randomized subjects, grouped per treatment assigned by randomization, regardless of the actual treatment received. This endpoint is reported here for Part B only as per the planned analysis.
    End point type
    Primary
    End point timeframe
    Approximately up to 2.5 years
    Notes
    [1] - 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 was planned to be reported for the specified arms only.
    End point values
    		 Part B: Decitabine (Alone) Part B: Decitabine + JNJ-56022473
    Number of subjects analysed
    159
    157
    Units: Percentage of subjects
        number (not applicable)
    11.9
    16.6
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Part B: Decitabine + JNJ-56022473 v Part B: Decitabine (Alone)
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4747
    Method
    		 Chi-squared
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 2.8

    Primary: Part B: Overall Survival

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    End point title
    		 Part B: Overall Survival [2]
    End point description
    Overall Survival (OS) was defined as the time from the date of randomization to date of death from any cause. Median Overall Survival was estimated by using the Kaplan-Meier method. ITT population is defined as all randomized subjects, grouped per treatment assigned by randomization, regardless of the actual treatment received. This endpoint is reported here for Part B only as per the planned analysis.
    End point type
    Primary
    End point timeframe
    Approximately up to 2.5 years
    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 was planned to be reported for the specified arms only.
    End point values
    		 Part B: Decitabine (Alone) Part B: Decitabine + JNJ-56022473
    Number of subjects analysed
    159
    157
    Units: Months
        median (confidence interval 95%)
    7.26 (6.47 to 8.64)
    5.36 (4.27 to 7.95)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Part B: Decitabine + JNJ-56022473 v Part B: Decitabine (Alone)
    Number of subjects included in analysis
    316
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7817
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.37

    Secondary: Part B: Event-free Survival (EFS) Based on Investigator Assessment

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    End point title
    		 Part B: Event-free Survival (EFS) Based on Investigator Assessment [3]
    End point description
    EFS:time from randomization to treatment failure(TF),relapse from CR/CRi, death from any cause, whichever occurs first,per modified IWG criteria. TF:>25% absolute increase in bone marrow blast count from baseline to present assessment (20%-46%) on bone marrow aspirate or biopsy in case of dry tap; Relapse:Bone marrow blasts >=5%; reappearance of blasts in blood; development of extramedullary disease (ED); CR:Bone marrow blasts <5 %; absence of blasts with Auer rods(AR); absence of extramedullary disease; absolute neutrophil count>1.0*10^9/L(1000/mcL);platelet count>100*10^9/L(100 000/mcL);independence of red cell transfusions; CRi:Bone marrow blasts <5%; absence of blasts with AR; absence of ED; residual neutropenia <1.0*10^9/L(1000/mcL), thrombocytopenia<100*10^9/L(100 000/mcL);independence of red cell transfusions. ITT: all randomized subjects,grouped per treatment assigned by randomization, regardless treatment received. Endpoint is reported here for Part B per planned analysis.
    End point type
    Secondary
    End point timeframe
    Approximately up to 2.5 years
    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 was planned to be reported for the specified arms only.
    End point values
    		 Part B: Decitabine (Alone) Part B: Decitabine + JNJ-56022473
    Number of subjects analysed
    159
    157
    Units: Months
        median (confidence interval 95%)
    6.24 (4.96 to 6.83)
    4.50 (3.61 to 6.74)
    No statistical analyses for this end point

    Secondary: Part B: Percentage of Subjects who Achieved CR and CRi (Overall Response Rate)

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    End point title
    		 Part B: Percentage of Subjects who Achieved CR and CRi (Overall Response Rate) [4]
    End point description
    The Percentage of subjects who achieved CR and CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0 *10^9/liter (L) (1000/ mcL); platelet count >100 *10^9/L (100 000/mcL); independence of red cell transfusions. CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. ITT population: all randomized subjects, grouped per treatment assigned by randomization, regardless of actual treatment received. The Endpoint is reported here for Part B only as per planned analysis.
    End point type
    Secondary
    End point timeframe
    Approximately up to 2.5 years
    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 was planned to be reported for the specified arms only.
    End point values
    		 Part B: Decitabine (Alone) Part B: Decitabine + JNJ-56022473
    Number of subjects analysed
    159
    157
    Units: Percentage of subjects
        number (not applicable)
    20.1
    26.8
    No statistical analyses for this end point

    Secondary: Part B: Percentage of Subjects With Complete Response (CR) Plus Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi)

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    End point title
    		 Part B: Percentage of Subjects With Complete Response (CR) Plus Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi) [5]
    End point description
    Percentage of subjects who achieved CR plus MRD-negative CRi were reported. MRD negativity defined as <1 blast or leukemic stem cell in 10,000 leukocytes (MRD level <10^4).CR: Bone marrow blasts less than (<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0*10^9/liter (L) (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions. CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. Population included subjects in ITT, among whom MRD negativity was evaluated upon achieving response. This endpoint is reported here for Part B only as per the planned analysis.
    End point type
    Secondary
    End point timeframe
    Approximately 2.5 years
    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 was planned to be reported for the specified arms only.
    End point values
    		 Part B: Decitabine (Alone) Part B: Decitabine + JNJ-56022473
    Number of subjects analysed
    80
    80
    Units: Percentage of subjects
        number (not applicable)
    13.8
    21.3
    No statistical analyses for this end point

    Secondary: Part B: Time to Best Response

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    End point title
    		 Part B: Time to Best Response [6]
    End point description
    Time to best response is calculated as the time from the randomization date to the first documented date for the best response for subjects who achieved CR or CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0 *10^9/liter (L) (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. Population included subjects in ITT, who achieved CR or CRi. This endpoint is reported here for Part B only as per the planned analysis.
    End point type
    Secondary
    End point timeframe
    Approximately 2.5 years
    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 was planned to be reported for the specified arms only.
    End point values
    		 Part B: Decitabine (Alone) Part B: Decitabine + JNJ-56022473
    Number of subjects analysed
    32
    42
    Units: Weeks
        median (full range (min-max))
    16.71 (7.1 to 41.6)
    18.14 (7.3 to 68.4)
    No statistical analyses for this end point

    Secondary: Part B: Duration of Best Response (DOR) Based on Investigator Assessment

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    End point title
    		 Part B: Duration of Best Response (DOR) Based on Investigator Assessment [7]
    End point description
    DOR: number of weeks from documented best response (CR/CRi) who achieved CR/CRi to relapse, death due to relapse, date of censoring. Per modified IWG criteria: CR: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease;absolute neutrophil count>1.0*10^9/L(1000/ mcL);platelet count >100*10^9/L (100 000/mcL);independence of red cell transfusions; CRi:Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease;residual neutropenia <1.0*10^9/L(1000/mcL) or thrombocytopenia <100*10^9/L(100 000/mcL);independence of red cell transfusions. "99999" indicates Median (Decitabine+JNJ-56022473 arm) and upper limit of 95% CI(Decitabine and Decitabine+JNJ-56022473 arm) was not estimable due to insufficient number of events. ITT population, who achieved CR or CRi. Endpoint reported is for Part B as per planned analysis.
    End point type
    Secondary
    End point timeframe
    Approximately 2.5 years
    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 was planned to be reported for the specified arms only.
    End point values
    		 Part B: Decitabine (Alone) Part B: Decitabine + JNJ-56022473
    Number of subjects analysed
    32
    42
    Units: Weeks
        median (confidence interval 95%)
    23.71 (15.43 to 99999)
    99999 (29.86 to 99999)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 2.5 years
    Adverse event reporting additional description
    Safety Population defined as randomized subjects who received at least one dose of study medication, grouped according to actual treatment received (9 subjects from decitabine + JNJ-56022473 arm were grouped in the decitabine alone arm as they received only decitabine and not JNJ 56022473).
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Part A: Decitabine + JNJ-56022473
    Reporting group description
    		 Subjects received 1 dose of JNJ-56022473 (talacotuzumab) at 9 milligram per kilogram (mg/kg) as intravenous (IV) infusion on Day 1 of cycle 1. From cycle 2 onwards, subjects received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death.

    Reporting group title
    Part B: Decitabine
    Reporting group description
    		 Subjects received decitabine on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death.

    Reporting group title
    Part B: Decitabine + JNJ-56022473
    Reporting group description
    		 Subjects received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death.

    Serious adverse events
    		 Part A: Decitabine + JNJ-56022473 Part B: Decitabine Part B: Decitabine + JNJ-56022473
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 10 (90.00%)
    120 / 165 (72.73%)
    126 / 147 (85.71%)
         number of deaths (all causes)
    10
    105
    91
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute Myeloid Leukaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder Neoplasm
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Central Nervous System Leukaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chloroma
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal Adenoma
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transitional Cell Carcinoma
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma Gastric
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic Hypotension
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemodynamic Instability
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Catheter Site Inflammation
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest Pain
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General Physical Health Deterioration
         subjects affected / exposed
    1 / 10 (10.00%)
    6 / 165 (3.64%)
    4 / 147 (2.72%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
    0 / 5
         deaths causally related to treatment / all
    1 / 1
    3 / 3
    0 / 3
    Hyperthermia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Influenza Like Illness
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple Organ Dysfunction Syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    9 / 165 (5.45%)
    9 / 147 (6.12%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 11
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    9 / 9
    0 / 8
    Pyrexia
         subjects affected / exposed
    1 / 10 (10.00%)
    9 / 165 (5.45%)
    15 / 147 (10.20%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 12
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden Death
         subjects affected / exposed
    0 / 10 (0.00%)
    5 / 165 (3.03%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    5 / 5
    0 / 1
    Condition Aggravated
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic Reaction
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic Shock
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Serum Sickness
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute Pulmonary Oedema
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute Respiratory Distress Syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Acute Respiratory Failure
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 165 (1.21%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    Bronchopneumopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 165 (0.61%)
    4 / 147 (2.72%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung Infiltration
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal Pain
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural Effusion
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Hypertension
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Oedema
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Respiratory Failure
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 165 (1.82%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    2 / 2
    0 / 2
    Respiratory Tract Haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Wheezing
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood Lactate Dehydrogenase Increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    C-Reactive Protein Increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 165 (1.82%)
    4 / 147 (2.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral Neck Fracture
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur Fracture
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Head Injury
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip Fracture
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Humerus Fracture
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal Compression Fracture
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transfusion Reaction
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transfusion-Related Acute Lung Injury
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic Haematoma
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute Myocardial Infarction
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina Pectoris
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial Fibrillation
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    5 / 147 (3.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac Arrest
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    5 / 147 (3.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 2
    Cardiac Failure
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    Cardiac Failure Acute
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    Cardiogenic Shock
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiopulmonary Failure
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    Cardiovascular Insufficiency
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Myocardial Ischaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pericardial Effusion
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular Tachycardia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular Accident
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage Intracranial
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Haemorrhagic Stroke
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Ischaemic Stroke
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral Sensory Neuropathy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Quadriparesis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    4 / 147 (2.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient Ischaemic Attack
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular Encephalopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    6 / 165 (3.64%)
    4 / 147 (2.72%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disseminated Intravascular Coagulation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Febrile Bone Marrow Aplasia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile Neutropenia
         subjects affected / exposed
    2 / 10 (20.00%)
    36 / 165 (21.82%)
    40 / 147 (27.21%)
         occurrences causally related to treatment / all
    0 / 2
    26 / 49
    0 / 67
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Splenomegaly
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 10 (0.00%)
    5 / 165 (3.03%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Ear Pain
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute Abdomen
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal Ulcer
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis Ulcerative
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 165 (1.82%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticular Perforation
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulum Intestinal
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis Erosive
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Angiodysplasia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Inflammation
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Polyp Haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal Haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large Intestinal Obstruction
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mechanical Ileus
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis Acute
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal Haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small Intestinal Obstruction
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 165 (0.61%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric Haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper Gastrointestinal Haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Cholangitis Acute
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis Acute
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperhidrosis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash Vesicular
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    4 / 147 (2.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anuria
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus Urinary
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oliguria
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal Impairment
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary Retention
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chondrocalcinosis Pyrophosphate
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular Weakness
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in Extremity
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Actinomycotic Pulmonary Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Alveolar Osteitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspergillus Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial Sepsis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    Bronchitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchopulmonary Aspergillosis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Candida Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Catheter Site Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridial Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium Difficile Colitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium Difficile Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device Related Infection
         subjects affected / exposed
    2 / 10 (20.00%)
    3 / 165 (1.82%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device Related Sepsis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterobacter Bacteraemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia Bacteraemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Escherichia Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia Sepsis
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia Urinary Tract Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fungaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis Rotavirus
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis Viral
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Candidiasis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic Infection Fungal
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected Skin Ulcer
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infectious Colitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Klebsiella Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver Abscess
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower Respiratory Tract Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung Infection
         subjects affected / exposed
    4 / 10 (40.00%)
    5 / 165 (3.03%)
    3 / 147 (2.04%)
         occurrences causally related to treatment / all
    0 / 5
    2 / 6
    0 / 3
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Moraxella Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenic Sepsis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Oral Candidiasis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parainfluenzae Virus Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parotitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periorbital Cellulitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis Jirovecii Pneumonia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 10 (0.00%)
    23 / 165 (13.94%)
    24 / 147 (16.33%)
         occurrences causally related to treatment / all
    0 / 0
    15 / 39
    0 / 29
         deaths causally related to treatment / all
    0 / 0
    9 / 9
    0 / 5
    Pneumonia Fungal
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudomembranous Colitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Mycosis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pyelonephritis Acute
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis Chronic
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Rash Pustular
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory Tract Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    4 / 147 (2.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    Rhinovirus Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 10 (20.00%)
    6 / 165 (3.64%)
    14 / 147 (9.52%)
         occurrences causally related to treatment / all
    0 / 3
    2 / 6
    0 / 21
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    0 / 7
    Septic Encephalopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic Shock
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 165 (1.21%)
    8 / 147 (5.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 5
    Sinusitis Fungal
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin Infection
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 165 (0.61%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Splenic Abscess
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal Infection
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal Sepsis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tooth Abscess
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tooth Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    4 / 165 (2.42%)
    6 / 147 (4.08%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vulval Cellulitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperuricaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part A: Decitabine + JNJ-56022473 Part B: Decitabine Part B: Decitabine + JNJ-56022473
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 10 (90.00%)
    157 / 165 (95.15%)
    146 / 147 (99.32%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 10 (0.00%)
    13 / 165 (7.88%)
    24 / 147 (16.33%)
         occurrences all number
    0
    17
    33
    Hypotension
         subjects affected / exposed
    1 / 10 (10.00%)
    17 / 165 (10.30%)
    22 / 147 (14.97%)
         occurrences all number
    1
    17
    29
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 10 (20.00%)
    25 / 165 (15.15%)
    26 / 147 (17.69%)
         occurrences all number
    5
    45
    44
    Chills
         subjects affected / exposed
    3 / 10 (30.00%)
    7 / 165 (4.24%)
    30 / 147 (20.41%)
         occurrences all number
    3
    8
    44
    Fatigue
         subjects affected / exposed
    1 / 10 (10.00%)
    31 / 165 (18.79%)
    31 / 147 (21.09%)
         occurrences all number
    3
    37
    41
    Oedema Peripheral
         subjects affected / exposed
    5 / 10 (50.00%)
    25 / 165 (15.15%)
    46 / 147 (31.29%)
         occurrences all number
    9
    44
    70
    Pain
         subjects affected / exposed
    0 / 10 (0.00%)
    5 / 165 (3.03%)
    8 / 147 (5.44%)
         occurrences all number
    0
    8
    8
    Pyrexia
         subjects affected / exposed
    6 / 10 (60.00%)
    46 / 165 (27.88%)
    51 / 147 (34.69%)
         occurrences all number
    11
    91
    79
    Gait Disturbance
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences all number
    2
    0
    1
    General Physical Health Deterioration
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 165 (1.21%)
    1 / 147 (0.68%)
         occurrences all number
    1
    2
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 10 (10.00%)
    15 / 165 (9.09%)
    16 / 147 (10.88%)
         occurrences all number
    1
    23
    22
    Dyspnoea
         subjects affected / exposed
    3 / 10 (30.00%)
    23 / 165 (13.94%)
    22 / 147 (14.97%)
         occurrences all number
    5
    25
    27
    Epistaxis
         subjects affected / exposed
    1 / 10 (10.00%)
    13 / 165 (7.88%)
    20 / 147 (13.61%)
         occurrences all number
    1
    17
    24
    Hypoxia
         subjects affected / exposed
    1 / 10 (10.00%)
    7 / 165 (4.24%)
    8 / 147 (5.44%)
         occurrences all number
    1
    8
    15
    Oropharyngeal Pain
         subjects affected / exposed
    0 / 10 (0.00%)
    7 / 165 (4.24%)
    9 / 147 (6.12%)
         occurrences all number
    0
    9
    11
    Pleural Effusion
         subjects affected / exposed
    1 / 10 (10.00%)
    10 / 165 (6.06%)
    4 / 147 (2.72%)
         occurrences all number
    1
    13
    4
    Bronchospasm
         subjects affected / exposed
    3 / 10 (30.00%)
    1 / 165 (0.61%)
    6 / 147 (4.08%)
         occurrences all number
    3
    2
    7
    Pharyngeal Oedema
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 10 (20.00%)
    13 / 165 (7.88%)
    16 / 147 (10.88%)
         occurrences all number
    2
    16
    21
    Adjustment Disorder with Depressed Mood
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Agitation
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 165 (1.82%)
    4 / 147 (2.72%)
         occurrences all number
    1
    3
    6
    Depressed Mood
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Hallucination
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 165 (1.21%)
    1 / 147 (0.68%)
         occurrences all number
    1
    2
    1
    Nervousness
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 10 (0.00%)
    5 / 165 (3.03%)
    9 / 147 (6.12%)
         occurrences all number
    0
    5
    12
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    0 / 10 (0.00%)
    5 / 165 (3.03%)
    8 / 147 (5.44%)
         occurrences all number
    0
    6
    10
    Blood Creatinine Increased
         subjects affected / exposed
    0 / 10 (0.00%)
    4 / 165 (2.42%)
    8 / 147 (5.44%)
         occurrences all number
    0
    4
    12
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 165 (0.61%)
    8 / 147 (5.44%)
         occurrences all number
    1
    1
    11
    Weight Decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    10 / 165 (6.06%)
    16 / 147 (10.88%)
         occurrences all number
    0
    12
    22
    Bacterial Test Positive
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    1 / 147 (0.68%)
         occurrences all number
    2
    0
    1
    Hepatic Enzyme Increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    International Normalised Ratio Increased
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 165 (1.82%)
    4 / 147 (2.72%)
         occurrences all number
    1
    3
    5
    Oxygen Saturation Decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    4 / 147 (2.72%)
         occurrences all number
    1
    0
    4
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 10 (0.00%)
    5 / 165 (3.03%)
    8 / 147 (5.44%)
         occurrences all number
    0
    5
    9
    Fall
         subjects affected / exposed
    0 / 10 (0.00%)
    9 / 165 (5.45%)
    13 / 147 (8.84%)
         occurrences all number
    0
    11
    19
    Cardiac disorders
    Atrial Fibrillation
         subjects affected / exposed
    0 / 10 (0.00%)
    8 / 165 (4.85%)
    13 / 147 (8.84%)
         occurrences all number
    0
    8
    17
    Tachycardia
         subjects affected / exposed
    1 / 10 (10.00%)
    6 / 165 (3.64%)
    14 / 147 (9.52%)
         occurrences all number
    2
    7
    15
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 10 (10.00%)
    9 / 165 (5.45%)
    14 / 147 (9.52%)
         occurrences all number
    1
    10
    17
    Headache
         subjects affected / exposed
    1 / 10 (10.00%)
    15 / 165 (9.09%)
    16 / 147 (10.88%)
         occurrences all number
    1
    20
    17
    Syncope
         subjects affected / exposed
    2 / 10 (20.00%)
    5 / 165 (3.03%)
    6 / 147 (4.08%)
         occurrences all number
    2
    6
    9
    Somnolence
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 165 (1.21%)
    2 / 147 (1.36%)
         occurrences all number
    1
    2
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 10 (70.00%)
    80 / 165 (48.48%)
    77 / 147 (52.38%)
         occurrences all number
    27
    286
    260
    Febrile Neutropenia
         subjects affected / exposed
    4 / 10 (40.00%)
    22 / 165 (13.33%)
    25 / 147 (17.01%)
         occurrences all number
    7
    32
    34
    Leukocytosis
         subjects affected / exposed
    0 / 10 (0.00%)
    9 / 165 (5.45%)
    1 / 147 (0.68%)
         occurrences all number
    0
    10
    1
    Leukopenia
         subjects affected / exposed
    1 / 10 (10.00%)
    15 / 165 (9.09%)
    12 / 147 (8.16%)
         occurrences all number
    1
    75
    38
    Neutropenia
         subjects affected / exposed
    1 / 10 (10.00%)
    61 / 165 (36.97%)
    64 / 147 (43.54%)
         occurrences all number
    11
    196
    201
    Thrombocytopenia
         subjects affected / exposed
    3 / 10 (30.00%)
    86 / 165 (52.12%)
    81 / 147 (55.10%)
         occurrences all number
    7
    341
    252
    Splenomegaly
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 165 (1.21%)
    2 / 147 (1.36%)
         occurrences all number
    1
    2
    2
    Ear and labyrinth disorders
    Tympanic Membrane Disorder
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Eye disorders
    Uveitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    1 / 10 (10.00%)
    12 / 165 (7.27%)
    19 / 147 (12.93%)
         occurrences all number
    1
    14
    28
    Abdominal Pain Upper
         subjects affected / exposed
    2 / 10 (20.00%)
    6 / 165 (3.64%)
    9 / 147 (6.12%)
         occurrences all number
    3
    6
    12
    Anal Incontinence
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 165 (0.00%)
    10 / 147 (6.80%)
         occurrences all number
    0
    0
    11
    Constipation
         subjects affected / exposed
    3 / 10 (30.00%)
    51 / 165 (30.91%)
    47 / 147 (31.97%)
         occurrences all number
    4
    71
    69
    Diarrhoea
         subjects affected / exposed
    4 / 10 (40.00%)
    41 / 165 (24.85%)
    50 / 147 (34.01%)
         occurrences all number
    5
    68
    75
    Dyspepsia
         subjects affected / exposed
    1 / 10 (10.00%)
    5 / 165 (3.03%)
    10 / 147 (6.80%)
         occurrences all number
    1
    5
    12
    Gingival Bleeding
         subjects affected / exposed
    0 / 10 (0.00%)
    10 / 165 (6.06%)
    2 / 147 (1.36%)
         occurrences all number
    0
    11
    2
    Haemorrhoids
         subjects affected / exposed
    1 / 10 (10.00%)
    8 / 165 (4.85%)
    21 / 147 (14.29%)
         occurrences all number
    1
    8
    22
    Nausea
         subjects affected / exposed
    5 / 10 (50.00%)
    33 / 165 (20.00%)
    36 / 147 (24.49%)
         occurrences all number
    10
    44
    58
    Stomatitis
         subjects affected / exposed
    1 / 10 (10.00%)
    16 / 165 (9.70%)
    12 / 147 (8.16%)
         occurrences all number
    1
    17
    17
    Toothache
         subjects affected / exposed
    0 / 10 (0.00%)
    9 / 165 (5.45%)
    4 / 147 (2.72%)
         occurrences all number
    0
    9
    4
    Vomiting
         subjects affected / exposed
    5 / 10 (50.00%)
    19 / 165 (11.52%)
    26 / 147 (17.69%)
         occurrences all number
    8
    32
    42
    Abdominal Discomfort
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 165 (0.61%)
    6 / 147 (4.08%)
         occurrences all number
    1
    1
    7
    Parotid Gland Enlargement
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Upper Gastrointestinal Haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    7 / 165 (4.24%)
    3 / 147 (2.04%)
         occurrences all number
    2
    12
    4
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    0 / 10 (0.00%)
    4 / 165 (2.42%)
    9 / 147 (6.12%)
         occurrences all number
    0
    5
    11
    Petechiae
         subjects affected / exposed
    1 / 10 (10.00%)
    10 / 165 (6.06%)
    11 / 147 (7.48%)
         occurrences all number
    1
    11
    12
    Pruritus
         subjects affected / exposed
    1 / 10 (10.00%)
    12 / 165 (7.27%)
    11 / 147 (7.48%)
         occurrences all number
    1
    12
    15
    Rash
         subjects affected / exposed
    1 / 10 (10.00%)
    11 / 165 (6.67%)
    13 / 147 (8.84%)
         occurrences all number
    1
    11
    16
    Hyperhidrosis
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 165 (1.21%)
    7 / 147 (4.76%)
         occurrences all number
    1
    2
    7
    Dry Skin
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 165 (1.82%)
    2 / 147 (1.36%)
         occurrences all number
    1
    3
    2
    Hidradenitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Purpura
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 165 (0.61%)
    0 / 147 (0.00%)
         occurrences all number
    1
    1
    0
    Skin Ulcer
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 165 (1.21%)
    3 / 147 (2.04%)
         occurrences all number
    1
    3
    4
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 10 (0.00%)
    7 / 165 (4.24%)
    11 / 147 (7.48%)
         occurrences all number
    0
    7
    15
    Urinary Incontinence
         subjects affected / exposed
    0 / 10 (0.00%)
    5 / 165 (3.03%)
    10 / 147 (6.80%)
         occurrences all number
    0
    6
    11
    Renal Impairment
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 165 (1.82%)
    5 / 147 (3.40%)
         occurrences all number
    1
    4
    9
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 10 (10.00%)
    15 / 165 (9.09%)
    12 / 147 (8.16%)
         occurrences all number
    1
    16
    16
    Back Pain
         subjects affected / exposed
    0 / 10 (0.00%)
    18 / 165 (10.91%)
    19 / 147 (12.93%)
         occurrences all number
    0
    19
    26
    Pain in Extremity
         subjects affected / exposed
    0 / 10 (0.00%)
    12 / 165 (7.27%)
    15 / 147 (10.20%)
         occurrences all number
    0
    18
    22
    Muscle Spasms
         subjects affected / exposed
    1 / 10 (10.00%)
    4 / 165 (2.42%)
    2 / 147 (1.36%)
         occurrences all number
    1
    4
    2
    Muscular Weakness
         subjects affected / exposed
    1 / 10 (10.00%)
    4 / 165 (2.42%)
    2 / 147 (1.36%)
         occurrences all number
    1
    4
    3
    Musculoskeletal Chest Pain
         subjects affected / exposed
    1 / 10 (10.00%)
    4 / 165 (2.42%)
    1 / 147 (0.68%)
         occurrences all number
    1
    4
    1
    Myalgia
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 165 (1.82%)
    4 / 147 (2.72%)
         occurrences all number
    1
    3
    4
    Infections and infestations
    Oral Candidiasis
         subjects affected / exposed
    2 / 10 (20.00%)
    6 / 165 (3.64%)
    9 / 147 (6.12%)
         occurrences all number
    2
    8
    11
    Oral Herpes
         subjects affected / exposed
    3 / 10 (30.00%)
    9 / 165 (5.45%)
    11 / 147 (7.48%)
         occurrences all number
    3
    13
    14
    Pneumonia
         subjects affected / exposed
    1 / 10 (10.00%)
    19 / 165 (11.52%)
    19 / 147 (12.93%)
         occurrences all number
    1
    24
    25
    Urinary Tract Infection
         subjects affected / exposed
    0 / 10 (0.00%)
    13 / 165 (7.88%)
    13 / 147 (8.84%)
         occurrences all number
    0
    15
    19
    Bronchitis
         subjects affected / exposed
    1 / 10 (10.00%)
    5 / 165 (3.03%)
    5 / 147 (3.40%)
         occurrences all number
    1
    5
    9
    Lung Infection
         subjects affected / exposed
    1 / 10 (10.00%)
    4 / 165 (2.42%)
    2 / 147 (1.36%)
         occurrences all number
    1
    4
    2
    Lymph Gland Infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Oropharyngeal Candidiasis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    2 / 147 (1.36%)
         occurrences all number
    1
    0
    3
    Respiratory Tract Infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    3 / 147 (2.04%)
         occurrences all number
    1
    0
    3
    Skin Infection
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 165 (1.82%)
    2 / 147 (1.36%)
         occurrences all number
    1
    4
    5
    Systemic Mycosis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Tooth Abscess
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 165 (0.00%)
    0 / 147 (0.00%)
         occurrences all number
    1
    0
    0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 10 (10.00%)
    6 / 165 (3.64%)
    2 / 147 (1.36%)
         occurrences all number
    1
    6
    2
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    4 / 10 (40.00%)
    31 / 165 (18.79%)
    25 / 147 (17.01%)
         occurrences all number
    4
    38
    37
    Hyperglycaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    4 / 165 (2.42%)
    17 / 147 (11.56%)
         occurrences all number
    0
    4
    25
    Hyperuricaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    8 / 165 (4.85%)
    9 / 147 (6.12%)
         occurrences all number
    0
    11
    12
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    5 / 165 (3.03%)
    13 / 147 (8.84%)
         occurrences all number
    0
    7
    15
    Hypocalcaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    9 / 165 (5.45%)
    14 / 147 (9.52%)
         occurrences all number
    1
    16
    16
    Hypokalaemia
         subjects affected / exposed
    3 / 10 (30.00%)
    41 / 165 (24.85%)
    53 / 147 (36.05%)
         occurrences all number
    5
    64
    99
    Hypomagnesaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    12 / 165 (7.27%)
    20 / 147 (13.61%)
         occurrences all number
    4
    20
    25
    Hypophosphataemia
         subjects affected / exposed
    1 / 10 (10.00%)
    5 / 165 (3.03%)
    9 / 147 (6.12%)
         occurrences all number
    2
    6
    9
    Fluid Overload
         subjects affected / exposed
    1 / 10 (10.00%)
    4 / 165 (2.42%)
    6 / 147 (4.08%)
         occurrences all number
    1
    5
    6
    Fluid Retention
         subjects affected / exposed
    1 / 10 (10.00%)
    4 / 165 (2.42%)
    1 / 147 (0.68%)
         occurrences all number
    2
    6
    2
    Hyperkalaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    4 / 165 (2.42%)
    5 / 147 (3.40%)
         occurrences all number
    1
    5
    9
    Hypoglycaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 165 (1.21%)
    2 / 147 (1.36%)
         occurrences all number
    1
    2
    2
    Hyponatraemia
         subjects affected / exposed
    1 / 10 (10.00%)
    7 / 165 (4.24%)
    4 / 147 (2.72%)
         occurrences all number
    1
    8
    11

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Jan 2016
    The overall reason for the amendment is that the study was originally designed as a Phase 2 study with a total of 120 subjects and a primary endpoint of event-free survival (EFS). An interim analysis with 45 EFS events was planned in the original study to determine if the study would be continued toward the end with 120 subjects. This amendment changes the primary endpoint of the study to 2 primary endpoints of complete response (CR) rate and overall survival (OS) and up to 400 subjects enrolled.
    28 Jun 2016
    This amendment was prepared in response to health authority review and clarifies inclusion criteria and the recommended dose of preinfusion medications prior to JNJ-56022473 administration
    29 Mar 2017
    The main reason of this amendment was to specify new guidance for patient monitoring and availability of resuscitation equipment during talacotuzumab infusion.
    26 Apr 2017
    The main reason of this amendment was to specify enhanced precautionary measures to mitigate infusion-related reactions for subjects receiving talacotuzumab infusion.
    02 Aug 2017
    The amendment was based on on Independent Data Monitoring Committee (IDMC) recommendation after results from the second interim analysis (final analysis for response endpoints and first analysis for overall survival [OS]) were reviewed. The IDMC recommended to close study enrollment and stop talacotuzumab treatment due to lack of efficacy in the talacotuzumab arm. Subjects in the combination arm should stop treatment of with talacotuzumab and can continue to receive DACOGEN only, in accordance with Principal Investigator decision and subject agreement.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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