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    Clinical Trial Results:
    A PHASE 1/2 DOSE ESCALATION AND COMBINATION COHORT STUDY TO EVALUATE THE SAFETY AND TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF BMS-986226 (ANTI-ICOS MAB) ALONE OR IN COMBINATION WITH NIVOLUMAB OR IPILIMUMAB IN PATIENTS WITH ADVANCED SOLID TUMORS

    Summary
    EudraCT number
    		 2017-000238-73
    Trial protocol
    		 ES  
    Global end of trial date
    20 Dec 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Jan 2023
    First version publication date
    01 Jan 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CA021-002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussee de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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
    22 Apr 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Dec 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To characterize the safety and tolerability of BMS-986226 administered alone and in combination with nivolumab or ipilimumab in participants with advanced solid tumors
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Sep 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Spain: 32
    Country: Number of subjects enrolled
    Switzerland: 15
    Country: Number of subjects enrolled
    United States: 28
    Worldwide total number of subjects
    80
    EEA total number of subjects
    32
    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)
    50
    From 65 to 84 years
    29
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 No participants were treated with BMS-986226 in combination with nivolumab (Parts B1 and B2) and no participants were treated in Parts D and E

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Preliminary - BMS-986226 2 mg
    Arm description
    		 Preliminary safety cohort participants received BMS-986226 2 mg every 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 2 mg every 4 weeks

    Arm title
    		 Preliminary - BMS-986226 8 mg
    Arm description
    		 Preliminary safety cohort participants received BMS-986226 8 mg every 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 8 mg every 4 weeks

    Arm title
    		 Part A - BMS-986226 25 mg
    Arm description
    		 Part A cohort participants received BMS-986226 25 mg every 4 weeks for 24 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 25 mg every 4 weeks

    Arm title
    		 Part A - BMS-986226 80 mg
    Arm description
    		 Part A cohort participants received BMS-986226 80 mg every 4 weeks for 24 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 80 mg every 4 weeks

    Arm title
    		 Part A - BMS-986226 200 mg
    Arm description
    		 Part A cohort participants received BMS-986226 200 mg every 4 weeks for 24 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 200 mg every 4 weeks

    Arm title
    		 Part A - BMS-986226 400 mg
    Arm description
    		 Part A cohort participants received BMS-986226 400 mg every 4 weeks for 24 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 400 mg every 4 weeks

    Arm title
    		 Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Arm description
    		 Part C1 cohort participants received BMS-986226 25 mg every 12 weeks plus Ipilimumab 3 mg/kg every 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 25 mg every 12 weeks

    Investigational medicinal product name
    Ipilimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ipilimumab 3 mg every 4 weeks

    Arm title
    		 Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg
    Arm description
    		 Part C1 cohort participants received BMS-986226 200 mg every 12 weeks plus Ipilimumab 3 mg/kg every 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 3 mg every 4 weeks

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 200 mg every 12 weeks

    Arm title
    		 Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Arm description
    		 Part C2 cohort participants received BMS-986226 25 mg every 4 weeks plus Ipilimumab 3 mg/kg every 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 3 mg every 4 weeks

    Investigational medicinal product name
    BMS-986226
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMS-986226 3 mg every 4 weeks

    Number of subjects in period 1
    		Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Started
    6
    7
    7
    11
    9
    9
    10
    12
    9
    Completed
    0
    0
    0
    0
    0
    0
    3
    1
    1
    Not completed
    6
    7
    7
    11
    9
    9
    7
    11
    8
         Adverse event, serious fatal
    -
    1
    -
    1
    1
    1
    -
    -
    -
         Adverse Event unrelated to study drug
    -
    -
    -
    1
    -
    1
    1
    -
    -
         Other Reasons
    -
    -
    -
    -
    -
    -
    -
    -
    1
         Study Drug Toxicity
    -
    -
    -
    1
    -
    -
    -
    -
    1
         Disease Progression
    6
    6
    7
    8
    8
    7
    6
    10
    6
         Participant request to discontinue study treatment
    -
    -
    -
    -
    -
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Preliminary - BMS-986226 2 mg
    Reporting group description
    		 Preliminary safety cohort participants received BMS-986226 2 mg every 4 weeks

    Reporting group title
    Preliminary - BMS-986226 8 mg
    Reporting group description
    		 Preliminary safety cohort participants received BMS-986226 8 mg every 4 weeks

    Reporting group title
    Part A - BMS-986226 25 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 25 mg every 4 weeks for 24 weeks

    Reporting group title
    Part A - BMS-986226 80 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 80 mg every 4 weeks for 24 weeks

    Reporting group title
    Part A - BMS-986226 200 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 200 mg every 4 weeks for 24 weeks

    Reporting group title
    Part A - BMS-986226 400 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 400 mg every 4 weeks for 24 weeks

    Reporting group title
    Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Reporting group description
    		 Part C1 cohort participants received BMS-986226 25 mg every 12 weeks plus Ipilimumab 3 mg/kg every 4 weeks

    Reporting group title
    Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg
    Reporting group description
    		 Part C1 cohort participants received BMS-986226 200 mg every 12 weeks plus Ipilimumab 3 mg/kg every 4 weeks

    Reporting group title
    Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Reporting group description
    		 Part C2 cohort participants received BMS-986226 25 mg every 4 weeks plus Ipilimumab 3 mg/kg every 4 weeks

    Reporting group values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Total
    Number of subjects
    		 6 7 7 11 9 9 10 12 9 80
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 4 5 4 7 5 4 7 7 7 50
        From 65-84 years
    		 2 2 3 4 4 5 3 4 2 29
        85 years and over
    		 0 0 0 0 0 0 0 1 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 59.3 ( 10.4 ) 58.3 ( 7.8 ) 63.6 ( 12.3 ) 62.5 ( 9.7 ) 55.3 ( 15.9 ) 61.7 ( 16.9 ) 55.7 ( 9.6 ) 62.3 ( 11.7 ) 58.3 ( 7.1 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 1 2 3 5 3 3 4 5 2 28
        Male
    		 5 5 4 6 6 6 6 7 7 52
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0 0 0 0
        Asian
    		 1 0 0 0 0 0 0 0 0 1
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0 0 1 0 2 3
        White
    		 4 6 6 10 9 9 7 12 6 69
        More than one race
    		 0 0 0 0 0 0 0 0 0 0
        Unknown or Not Reported
    		 1 1 1 1 0 0 2 0 1 7
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 1 1 1 0 0 1 1 0 1 6
        Not Hispanic or Latino
    		 5 5 4 5 4 2 6 8 5 44
        Unknown or Not Reported
    		 0 1 2 6 5 6 3 4 3 30

    End points

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    End points reporting groups
    Reporting group title
    Preliminary - BMS-986226 2 mg
    Reporting group description
    		 Preliminary safety cohort participants received BMS-986226 2 mg every 4 weeks

    Reporting group title
    Preliminary - BMS-986226 8 mg
    Reporting group description
    		 Preliminary safety cohort participants received BMS-986226 8 mg every 4 weeks

    Reporting group title
    Part A - BMS-986226 25 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 25 mg every 4 weeks for 24 weeks

    Reporting group title
    Part A - BMS-986226 80 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 80 mg every 4 weeks for 24 weeks

    Reporting group title
    Part A - BMS-986226 200 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 200 mg every 4 weeks for 24 weeks

    Reporting group title
    Part A - BMS-986226 400 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 400 mg every 4 weeks for 24 weeks

    Reporting group title
    Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Reporting group description
    		 Part C1 cohort participants received BMS-986226 25 mg every 12 weeks plus Ipilimumab 3 mg/kg every 4 weeks

    Reporting group title
    Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg
    Reporting group description
    		 Part C1 cohort participants received BMS-986226 200 mg every 12 weeks plus Ipilimumab 3 mg/kg every 4 weeks

    Reporting group title
    Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Reporting group description
    		 Part C2 cohort participants received BMS-986226 25 mg every 4 weeks plus Ipilimumab 3 mg/kg every 4 weeks

    Primary: The Number of Participants Experiencing Adverse Events (AEs)

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    End point title
    		 The Number of Participants Experiencing Adverse Events (AEs) [1]
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
    End point type
    Primary
    End point timeframe
    From first dose up to 100 days post last dose, up to approximately 31 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics were planned for this endpoint
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    6
    7
    7
    11
    9
    9
    10
    12
    9
    Units: Participants
    6
    7
    7
    11
    9
    9
    10
    12
    9
    No statistical analyses for this end point

    Primary: The Number of Participants Experiencing Serious Adverse Events (SAEs)

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    End point title
    		 The Number of Participants Experiencing Serious Adverse Events (SAEs) [2]
    End point description
    Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.
    End point type
    Primary
    End point timeframe
    From first dose up to 100 days post last dose, up to approximately 31 months
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics were planned for this endpoint
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    6
    7
    7
    11
    9
    9
    10
    12
    9
    Units: Participants
    2
    3
    2
    10
    5
    9
    5
    9
    5
    No statistical analyses for this end point

    Primary: The Number of Participants Experiencing Adverse Events Leading to Discontinuation

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    End point title
    		 The Number of Participants Experiencing Adverse Events Leading to Discontinuation [3]
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
    End point type
    Primary
    End point timeframe
    From first dose up to 100 days post last dose, up to approximately 31 months
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics were planned for this endpoint
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    6
    7
    7
    11
    9
    9
    10
    12
    9
    Units: Participants
    0
    0
    0
    1
    1
    4
    0
    3
    2
    No statistical analyses for this end point

    Primary: The Number of Participants Experiencing Adverse Events Resulting in Death

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    End point title
    		 The Number of Participants Experiencing Adverse Events Resulting in Death [4]
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
    End point type
    Primary
    End point timeframe
    From first dose up to 100 days post last dose, up to approximately 31 months
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics were planned for this endpoint
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    6
    7
    7
    11
    9
    9
    10
    12
    9
    Units: Participants
    5
    3
    5
    8
    5
    7
    7
    8
    5
    No statistical analyses for this end point

    Primary: The Number of Participants Experiencing Clinical Laboratory Abnormalities

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    End point title
    		 The Number of Participants Experiencing Clinical Laboratory Abnormalities [5]
    End point description
    The number of participants experiencing abnormal laboratory results of Grade 3 or higher. Laboratory values will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with Grade 3=severe and Grade 4=life threatening.
    End point type
    Primary
    End point timeframe
    From first dose up to 30 days post last dose (approximately 28 months)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics were planned for this endpoint
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    6
    7
    7
    11
    9
    9
    10
    12
    9
    Units: Participants
        HEMOGLOBIN
    1
    0
    0
    1
    1
    2
    0
    1
    1
        LYMPHOCYTES (ABSOLUTE)
    0
    1
    1
    3
    2
    3
    2
    4
    3
        LYMPHOCYTES (RELATIVE)
    0
    1
    0
    0
    0
    1
    1
    0
    0
        ALKALINE PHOSPHATASE
    0
    0
    0
    2
    1
    2
    3
    2
    0
        ASPARTATE AMINOTRANSFERASE
    0
    0
    0
    1
    1
    0
    1
    1
    1
        ALANINE AMINOTRANSFERASE
    0
    0
    0
    0
    1
    0
    1
    0
    1
        G-GLUTAMYL TRANSFERASE
    1
    2
    1
    4
    3
    2
    6
    3
    1
        BILIRUBIN, TOTAL
    0
    0
    0
    2
    1
    0
    0
    0
    0
        PHOSPHATE
    0
    0
    0
    0
    0
    1
    0
    1
    1
        LIPASE, TOTAL
    0
    1
    1
    0
    0
    0
    2
    1
    1
        HYPONATREMIA
    0
    0
    0
    0
    1
    1
    0
    0
    1
        HYPERKALEMIA
    0
    0
    0
    1
    0
    0
    0
    0
    0
        HYPERGLYCEMIA
    1
    0
    0
    0
    0
    0
    0
    0
    0
        HYPOKALEMIA
    0
    0
    0
    0
    0
    0
    1
    0
    0
    No statistical analyses for this end point

    Primary: The Number of Participants Experiencing Adverse Events (AEs) Meeting Dose Limiting Toxicity (DLT) Criteria

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    End point title
    		 The Number of Participants Experiencing Adverse Events (AEs) Meeting Dose Limiting Toxicity (DLT) Criteria [6]
    End point description
    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Dose limiting toxicity (DLT) is defined based on the incidence, intensity, and duration of AEs for which no clear alternative cause is identified. The DLT period will be 28 days (4 weeks) in the Preliminary Safety Cohorts. Any toxicities that occur beyond the 4-week DLT period will also be considered in dose-level decisions. For the purpose of participant management, any AE that meets DLT criteria, regardless of the cycle in which it occurs, will lead to discontinuation of study treatment. AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
    End point type
    Primary
    End point timeframe
    From first dose up to 100 days post last dose, up to approximately 31 months
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics were planned for this endpoint
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    6
    7
    7
    11
    9
    9
    10
    12
    9
    Units: Participants
    0
    0
    0
    1
    0
    0
    0
    1
    0
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR)

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    End point title
    		 Objective Response Rate (ORR)
    End point description
    ORR is defined as the percentage of all treated participants whose best overall response (BOR) is either complete response (CR) or partial response (PR) as assessed by investigator per RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must also have reduction in the short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. BOR for a participant is defined as the best response designation recorded between the date of first dose (or date of randomization) and the date of first objectively documented progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first.
    End point type
    Secondary
    End point timeframe
    From first dose up to documented disease progression, up to 48 months
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    6
    7
    7
    9
    9
    9
    10
    12
    9
    Units: Percentage of participants
        median (confidence interval 95%)
    0 (0.0 to 45.9)
    0 (0.0 to 41.0)
    0 (0.0 to 41.0)
    0 (0.0 to 28.5)
    0 (0.0 to 33.6)
    0 (0.0 to 33.6)
    0 (0.0 to 30.8)
    8.3 (0.2 to 38.5)
    0 (0.0 to 33.6)
    No statistical analyses for this end point

    Secondary: Median Duration of Response (DOR)

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    End point title
    		 Median Duration of Response (DOR)
    End point description
    DOR for a participant with confirmed response is defined as the time from the date of first response CR or PR to the date of first objectively documented tumor progression as determined using RECIST v1.1 or death due to any cause, whichever occurs first. Participant who remain alive and have not progressed will be censored on the date of their last tumor assessment. Participants who started subsequent anticancer therapy without a prior reported progression will be censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy. CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must also have reduction in the short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Secondary
    End point timeframe
    From first dose up to the date of the first objectively documented tumor progression or death, whichever occurs first (up to approximately 24 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    0 [7]
    0 [8]
    0 [9]
    0 [10]
    0 [11]
    0 [12]
    0 [13]
    1
    0 [14]
    Units: Months
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    23.4 (23.4 to 23.4)
    ( to )
    Notes
    [7] - Data not reported due to insufficient number of participants with evaluable responses.
    [8] - Data not reported due to insufficient number of participants with evaluable responses.
    [9] - Data not reported due to insufficient number of participants with evaluable responses.
    [10] - Data not reported due to insufficient number of participants with evaluable responses.
    [11] - Data not reported due to insufficient number of participants with evaluable responses.
    [12] - Data not reported due to insufficient number of participants with evaluable responses.
    [13] - Data not reported due to insufficient number of participants with evaluable responses.
    [14] - Data not reported due to insufficient number of participants with evaluable responses.
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) Rate at 24 Weeks

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    End point title
    		 Progression Free Survival (PFS) Rate at 24 Weeks
    End point description
    The PFSR is defined as the percentage of treated participants remaining progression free and surviving at the prespecified timepoint of 24 weeks since the first dosing date. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of 1 or more new lesions is also considered progression.)
    End point type
    Secondary
    End point timeframe
    At 24 weeks
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    6
    7
    7
    11
    9
    9
    10
    12
    9
    Units: Percentage of participants
        median (confidence interval 95%)
    16.7 (0.8 to 51.7)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    8.3 (0.5 to 31.1)
    18.8 (1.1 to 53.5)
    No statistical analyses for this end point

    Secondary: Accumulation Index - Area Under Curve (AI-AUC)

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    End point title
    		 Accumulation Index - Area Under Curve (AI-AUC)
    End point description
    Accumulation Index is defined as the extent of drug accumulation and determined by the ratio of plasma concentration at plateau over plasma concentration after the first dose. The area under curve is defined as the area under the plot of plasma concentration of a drug versus time after dosage which reflects the extent of exposure to a drug and its clearance rate from the body. "99999"=N/A Geometric Coefficient of Variation=%CV
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    0 [15]
    1
    0 [16]
    3
    4
    1
    0 [17]
    0 [18]
    0 [19]
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1
    ( )
    99999 ( 99999 )
    ( )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    ( )
    ( )
    ( )
        C2D1
    ( )
    99999 ( 99999 )
    ( )
    1.07 ( 9 )
    0.856 ( 14 )
    0.953 ( 99999 )
    ( )
    ( )
    ( )
        C3D1
    ( )
    0.100 ( 99999 )
    ( )
    0.808 ( 99999 )
    1.28 ( 99999 )
    99999 ( 99999 )
    ( )
    ( )
    ( )
    Notes
    [15] - Data not reported due to insufficient number of participants with evaluable responses.
    [16] - Data not reported due to insufficient number of participants with evaluable responses.
    [17] - Data not reported due to insufficient number of participants with evaluable responses.
    [18] - Data not reported due to insufficient number of participants with evaluable responses.
    [19] - Data not reported due to insufficient number of participants with evaluable responses.
    No statistical analyses for this end point

    Secondary: Accumulation Index - Cmax (AI-Cmax)

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    End point title
    		 Accumulation Index - Cmax (AI-Cmax)
    End point description
    Accumulation Index is defined as the extent of drug accumulation and determined by the ratio of plasma concentration at plateau over plasma concentration after the first dose. Cmax is the maximum serum concentration that a drug achieves after the drug has been administered and before the administration of a second dose. "99999"=N/A Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1 and C3D1. Pre-dose and 0.5 post dose on C4D1. (Approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    0 [20]
    1
    1
    3
    5
    4
    0 [21]
    1
    2
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1
    ( )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    ( )
    99999 ( 99999 )
    99999 ( 99999 )
        C2D1
    ( )
    0.475 ( 99999 )
    99999 ( 99999 )
    1.19 ( 99999 )
    0.951 ( 99999 )
    0.861 ( 99999 )
    ( )
    99999 ( 99999 )
    0.687 ( 23 )
        C3D1
    ( )
    0.457 ( 99999 )
    0.309 ( 99999 )
    0.920 ( 99999 )
    1.11 ( 99999 )
    0.940 ( 99999 )
    ( )
    99999 ( 99999 )
    1.11 ( 99999 )
        C4D1
    ( )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    ( )
    0.633 ( 99999 )
    99999 ( 99999 )
    Notes
    [20] - Data not reported due to insufficient number of participants with evaluable responses.
    [21] - Data not reported due to insufficient number of participants with evaluable responses.
    No statistical analyses for this end point

    Secondary: Number of Participants with Anti-Drug Antibodies (ADA) for BMS-986226

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    End point title
    		 Number of Participants with Anti-Drug Antibodies (ADA) for BMS-986226
    End point description
    ADA for BMS-986226 is defined as the number of participants found to have seroconverted or boosted their pre-existing ADA during the study period. Baseline ADA positive is defined as ADA is detected in the last sample before initiation of treatment. ADA positive is defined as 1) an ADA detected (positive seroconversion) sample in a participant for whom ADA is not detected at baseline, or (2) an ADA detected sample with ADA titer to be at least 4-fold or greater (≥) than baseline positive titer.
    End point type
    Secondary
    End point timeframe
    Predose on cycles 1-6, post dose on C1D15, and 30, 60, and 100 days post last dose (up to approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    5
    6
    6
    11
    9
    8
    8
    11
    9
    Units: Participants
        Baseline ADA Positive
    0
    0
    0
    1
    0
    1
    0
    0
    0
        ADA Positive after initiation of treatment
    4
    6
    3
    8
    4
    4
    8
    9
    8
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax)

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax)
    End point description
    Cmax is the maximum serum concentration that a drug achieves after the drug has been administered and before the administration of a second dose. "99999"=N/A Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    5
    7
    6
    11
    9
    8
    8
    11
    9
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1
    733 ( 37 )
    2250 ( 20 )
    6609 ( 23 )
    19524 ( 28 )
    41698 ( 33 )
    85905 ( 37 )
    5440 ( 35 )
    43309 ( 28 )
    3451 ( 99999 )
        C2D1
    99999 ( 99999 )
    1050 ( 99999 )
    7220 ( 99999 )
    23322 ( 16 )
    45054 ( 36 )
    91931 ( 108 )
    99999 ( 99999 )
    30200 ( 99999 )
    2697 ( 99999 )
        C3D1
    99999 ( 99999 )
    1060 ( 99999 )
    3168 ( 12 )
    15000 ( 99999 )
    41700 ( 99999 )
    76700 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    3880 ( 99999 )
    No statistical analyses for this end point

    Secondary: Effective Elimination Half-Life (T-HALFeff)

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    End point title
    		 Effective Elimination Half-Life (T-HALFeff)
    End point description
    Effective elimination half-life that explains the degree of accumulation observed "99999"=N/A
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C2D1 and C3D1 (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    0 [22]
    0 [23]
    0 [24]
    2
    1
    0 [25]
    0 [26]
    0 [27]
    0 [28]
    Units: Hours
    arithmetic mean (standard deviation)
        C2D1
    ( )
    ( )
    ( )
    212 ( 9.4 )
    102 ( 99999 )
    ( )
    ( )
    ( )
    ( )
        C3D1
    ( )
    ( )
    ( )
    99999 ( 99999 )
    308 ( 99999 )
    ( )
    ( )
    ( )
    ( )
    Notes
    [22] - Data not reported due to insufficient number of participants with evaluable responses.
    [23] - Data not reported due to insufficient number of participants with evaluable responses.
    [24] - Data not reported due to insufficient number of participants with evaluable responses.
    [25] - Data not reported due to insufficient number of participants with evaluable responses.
    [26] - Data not reported due to insufficient number of participants with evaluable responses.
    [27] - Data not reported due to insufficient number of participants with evaluable responses.
    [28] - Data not reported due to insufficient number of participants with evaluable responses.
    No statistical analyses for this end point

    Secondary: Trough Observed Serum Concentrations (Ctrough)

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    End point title
    		 Trough Observed Serum Concentrations (Ctrough)
    End point description
    Trough observed serum concentrations (Ctrough) is defined as the concentration reached by a drug immediately before the next dose is administered. "99999"=N/A
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C2D1 and C3D1. Pre-dose and 0.5 post dose on C4D1. Pre-dose on C5D1 and C6D1. Pre-dose and 0.5 hours post dose on C7D1. (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    1
    1
    2
    3
    5
    4
    1
    1
    1
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 2 Day 1
    99999 ( 99999 )
    12.5 ( 99999 )
    27.0 ( 99999 )
    943 ( 584.4 )
    1501 ( 1202.9 )
    1491 ( 1287.3 )
    12.5 ( 99999 )
    99999 ( 99999 )
    12.5 ( 99999 )
        Cycle 3 Day 1
    99999 ( 99999 )
    12.5 ( 99999 )
    27.2 ( 20.72 )
    892 ( 99999 )
    180 ( 99999 )
    3150 ( 99999 )
    12.5 ( 99999 )
    99999 ( 99999 )
    12.5 ( 99999 )
        Cycle 4 Day 1
    12.5 ( 99999 )
    99999 ( 99999 )
    12.5 ( 99999 )
    504 ( 99999 )
    800 ( 401.1 )
    99999 ( 99999 )
    12.5 ( 99999 )
    99999 ( 99999 )
    12.5 ( 99999 )
        Cycle 5 Day 1
    12.5 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    3300 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    12.5 ( 99999 )
        Cycle 6 Day 1
    12.5 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Cycle 7 Day 1
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    12.5 ( 99999 )
    12.5 ( 99999 )
    No statistical analyses for this end point

    Secondary: Time of Maximum Observed Serum Concentration (Tmax)

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    End point title
    		 Time of Maximum Observed Serum Concentration (Tmax)
    End point description
    Tmax is defined as the amount of time that a drug is present at the maximum concentration in serum. "99999"=N/A
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    6
    7
    6
    11
    9
    8
    8
    11
    9
    Units: Hours
    median (full range (min-max))
        C1D1
    4.00 (0.067 to 4.22)
    0.283 (0.133 to 4.00)
    0.534 (0.467 to 4.50)
    1.25 (0.467 to 21.7)
    3.88 (0.467 to 24.0)
    4.00 (0.500 to 24.0)
    2.88 (0.467 to 4.50)
    1.02 (0.483 to 18.9)
    0.600 (0.467 to 22.0)
        C2D1
    99999 (99999 to 99999)
    0.600 (0.600 to 0.600)
    0.967 (0.967 to 0.967)
    4.00 (0.483 to 4.00)
    1.00 (0.433 to 4.52)
    4.00 (0.383 to 4.00)
    99999 (99999 to 99999)
    2.83 (2.83 to 2.83)
    2.24 (0.483 to 4.00)
        C3D1
    99999 (99999 to 99999)
    0.133 (0.133 to 0.133)
    0.534 (0.517 to 0.550)
    0.467 (0.467 to 0.467)
    1.03 (1.03 to 1.03)
    0.967 (0.967 to 0.967)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    0.500 (0.500 to 0.500)
    No statistical analyses for this end point

    Secondary: Area Under Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Concentration [AUC (0-T)]

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    End point title
    		 Area Under Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Concentration [AUC (0-T)]
    End point description
    AUC(0-t) (partial AUC) is defined as the area under the concentration-time curve from dosing (time 0) to time t. AUC(0-t) may be computed for one or more values of t, with specific values of t determined after observing the data. "99999"=N/A Note: Coefficient of variation is reported in lieu of geometric coefficient of variation.
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    5
    7
    6
    11
    9
    8
    8
    11
    9
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1
    33704 ( 12 )
    175228 ( 33 )
    682168 ( 23 )
    1951486 ( 52 )
    4966612 ( 53 )
    8346408 ( 25 )
    370356 ( 41 )
    4805561 ( 60 )
    277927 ( 54 )
        C2D1
    99999 ( 99999 )
    13921 ( 99999 )
    933038 ( 99999 )
    3534177 ( 14 )
    5887547 ( 45 )
    4070442 ( 60 )
    99999 ( 99999 )
    2528949 ( 99999 )
    35464 ( 39 )
        C3D1
    99999 ( 99999 )
    18442 ( 99999 )
    81982 ( 128 )
    2727643 ( 99999 )
    5157593 ( 99999 )
    7511434 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    55178 ( 99999 )
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve in 1 Dosing Interval [AUC (TAU)]

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    End point title
    		 Area Under the Concentration-Time Curve in 1 Dosing Interval [AUC (TAU)]
    End point description
    AUC (TAU) is defined as the area under the plasma concentration-time curve from time zero to the end of the dosing interval. "99999"=N/A Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    5
    7
    6
    11
    9
    8
    8
    11
    9
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1
    37392 ( 18 )
    189031 ( 32 )
    704072 ( 22 )
    1992589 ( 51 )
    5148217 ( 51 )
    8740936 ( 26 )
    404651 ( 42 )
    5006775 ( 67 )
    301365 ( 53 )
        C2D1
    99999 ( 99999 )
    99999 ( 99999 )
    933038 ( 99999 )
    3693517 ( 12 )
    5766681 ( 55 )
    10833374 ( 4 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        C3D1
    99999 ( 99999 )
    19007 ( 99999 )
    373429 ( 99999 )
    2727643 ( 99999 )
    5157593 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Total Body Clearance (CLT)

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    End point title
    		 Total Body Clearance (CLT)
    End point description
    CLT is defined as the elimination of the drug from the body "99999"=N/A Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    0 [29]
    1
    1
    3
    4
    2
    0 [30]
    0 [31]
    0 [32]
    Units: mL/h
    geometric mean (geometric coefficient of variation)
        C1D1
    ( )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    ( )
    ( )
    ( )
        C2D1
    ( )
    99999 ( 99999 )
    26.8 ( 99999 )
    21.7 ( 13 )
    34.7 ( 59 )
    36.9 ( 4 )
    ( )
    ( )
    ( )
        C3D1
    ( )
    421 ( 99999 )
    99999 ( 99999 )
    29.3 ( 99999 )
    38.8 ( 99999 )
    99999 ( 99999 )
    ( )
    ( )
    ( )
    Notes
    [29] - Data not reported due to insufficient number of participants with evaluable responses.
    [30] - Data not reported due to insufficient number of participants with evaluable responses.
    [31] - Data not reported due to insufficient number of participants with evaluable responses.
    [32] - Data not reported due to insufficient number of participants with evaluable responses.
    No statistical analyses for this end point

    Secondary: Average Concentration over a Dosing Interval (Css-avg)

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    End point title
    		 Average Concentration over a Dosing Interval (Css-avg)
    End point description
    Css-avg is defined as the average concentration over a dosing interval (AUC[TAU]/tau) Note: Coefficient of variation is reported in lieu of geometric coefficient of variation "99999"=N/A
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1, and C3D1 (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    0 [33]
    1
    1
    3
    4
    2
    0 [34]
    0 [35]
    0 [36]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1
    ( )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    ( )
    ( )
    ( )
        C2D1
    ( )
    99999 ( 99999 )
    1397 ( 99999 )
    5499 ( 12 )
    8581 ( 55 )
    16115 ( 4 )
    ( )
    ( )
    ( )
        C3D1
    ( )
    28.3 ( 99999 )
    556 ( 99999 )
    4065 ( 99999 )
    7666 ( 99999 )
    99999 ( 99999 )
    ( )
    ( )
    ( )
    Notes
    [33] - Data not reported due to insufficient number of participants with evaluable responses.
    [34] - Data not reported due to insufficient number of participants with evaluable responses.
    [35] - Data not reported due to insufficient number of participants with evaluable responses.
    [36] - Data not reported due to insufficient number of participants with evaluable responses.
    No statistical analyses for this end point

    Secondary: Accumulation Index - Concentrations at the End of Dosing Interval (AI-CTAU)

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    End point title
    		 Accumulation Index - Concentrations at the End of Dosing Interval (AI-CTAU)
    End point description
    Accumulation Index is defined as the extent of drug accumulation and determined by the ratio of plasma concentration at plateau over plasma concentration after the first dose. "99999"=N/A Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    End point type
    Secondary
    End point timeframe
    Pre-dose, 0.5, 4, 24, 72, 168, 336, 504 hours post dose on C1D1, C2D1 and C3D1. Pre-dose and 0.5 post dose on C4D1. (Approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    0 [37]
    1
    0 [38]
    3
    4
    1
    0 [39]
    0 [40]
    0 [41]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        C1D1
    ( )
    99999 ( 99999 )
    ( )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    ( )
    ( )
    ( )
        C2D1
    ( )
    99999 ( 99999 )
    ( )
    0.640 ( 99999 )
    1.12 ( 99999 )
    1.38 ( 99999 )
    ( )
    ( )
    ( )
        C3D1
    ( )
    99999 ( 99999 )
    ( )
    0.391 ( 99999 )
    33.3 ( 99999 )
    99999 ( 99999 )
    ( )
    ( )
    ( )
        C4D1
    ( )
    99999 ( 99999 )
    ( )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    ( )
    ( )
    ( )
    Notes
    [37] - Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    [38] - Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    [39] - Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    [40] - Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    [41] - Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    No statistical analyses for this end point

    Secondary: Changes from Baseline in Cell Surface ICOS Expression on T Cells

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    End point title
    		 Changes from Baseline in Cell Surface ICOS Expression on T Cells
    End point description
    Summary measures of changes from baseline to the last evaluable time point in cell surface Inducible costimulator (ICOS) expression on T cells. Baseline = last non missing value prior or on to the first dosing. "99999"=N/A Note: Coefficient of variation is reported in lieu of geometric coefficient of variation
    End point type
    Secondary
    End point timeframe
    From baseline up to pre-dose and 4 hours post dose on C1D1 and pre-dose and 4 hours post dose on C2D1 (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    4
    6
    7
    10
    8
    9
    9
    10
    6
    Units: Melt Flow Index (MFI)
    median (full range (min-max))
        Baseline Response
    985.5 (554 to 1243)
    659.0 (455 to 775)
    878.0 (599 to 1361)
    482 (197 to 912)
    434.0 (169 to 884)
    634.0 (94 to 1166)
    592.0 (162 to 933)
    714.0 (234 to 1438)
    506.5 (20 to 943)
        C1D1- Pre-Dose
    -394.0 (-394 to 394)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    -636.0 (-636 to -636)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        C1D1- 4 hours post dose
    -1049.0 (-1049 to -1049)
    -603.0 (-603 to -603)
    -762.0 (-847 to -565)
    -391.0 (-635 to -176)
    -324.0 (-481 to -95)
    -545.0 (-1029 to -184)
    -382.5 (-649 to -116)
    -654.5 (-1405 to -214)
    -490.0 (-928 to -429)
        C2D1- Pre-Dose
    -421.0 (-729 to -31)
    -26.0 (-538 to 104)
    -414.0 (-1101 to 630)
    -153.0 (-774 to -38)
    -185.0 (-865 to -177)
    -627.0 (-632 to -622)
    -294.0 (-500 to 308)
    -185.5 (-1155 to 430)
    11.5 (-104 to 148)
        C2D1- 4 hours post dose
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    -167.5 (-229 to -106)
    -336.5 (-507 to -166)
    -567.0 (-615 to -372)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    -465.5 (-911 to 254)
    No statistical analyses for this end point

    Secondary: Changes from Baseline in ICOS Ligand+ B Cells

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    End point title
    		 Changes from Baseline in ICOS Ligand+ B Cells
    End point description
    Summary measures of changes from baseline to the last evaluable time point in ICOS ligand+ B cells in the tumor and peripheral blood. Baseline = last non missing value prior or on to the first dosing.
    End point type
    Secondary
    End point timeframe
    From baseline up to pre-dose and 4 hours post dose on C1D1, 72 hours post dose on C1D4, and pre-dose on C2D1 (approximately 31 months)
    End point values
    		 Preliminary - BMS-986226 2 mg Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Number of subjects analysed
    4
    6
    6
    10
    8
    9
    9
    10
    8
    Units: Melt Flow Index (MFI)
    median (full range (min-max))
        Baseline Response
    -9.0 (-94 to 185)
    -33.0 (-70 to 67)
    2.5 (-99 to 95)
    40.5 (-90 to 127)
    -60.5 (-171 to 74)
    57.0 (-100 to 182)
    -15.0 (-79 to 70)
    -11.5 (-113 to 41)
    39.0 (-56 to 103)
        C1D1 - 4 hours post dose
    -106.0 (-106 to -106)
    -2.0 (-2 to -2)
    -3.0 (-48 to 37)
    1.0 (-9 to 23)
    -13.5 (-55 to 0)
    9.5 (-16 to 99)
    3.5 (1 to 6)
    0.0 (-14 to 37)
    -6.0 (-21 to 40)
        C1D4- 72 hours post dose
    11.0 (-181 to 58)
    102.0 (-28 to 190)
    170.0 (118 to 210)
    37.0 (-143 to 231)
    64.5 (-71 to 127)
    29.0 (-106 to 88)
    90.0 (17 to 163)
    70.0 (3 to 143)
    33.5 (-28 to 121)
        C2D1- Pre dose
    -4.0 (-267 to 54)
    -24.0 (-211 to 24)
    96.0 (-167 to 207)
    -17.0 (-100 to 170)
    103.5 (-39 to 216)
    -28.0 (-74 to 18)
    -9.0 (-129 to 83)
    61.5 (-20 to 186)
    -17.0 (-175 to 103)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Participants were assessed for all-cause mortality from their enrollment to study completion, (up to approximately 50 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 31 months)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Preliminary - BMS-986226 8 mg
    Reporting group description
    		 Preliminary safety cohort participants received BMS-986226 8 mg every 4 weeks

    Reporting group title
    Part A - BMS-986226 25 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 25 mg every 4 weeks for 24 weeks

    Reporting group title
    Part A - BMS-986226 80 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 80 mg every 4 weeks for 24 weeks

    Reporting group title
    Part A - BMS-986226 200 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 200 mg every 4 weeks for 24 weeks

    Reporting group title
    Preliminary - BMS-986226 2 mg
    Reporting group description
    		 Preliminary safety cohort participants received BMS-986226 2 mg every 4 weeks

    Reporting group title
    Part A - BMS-986226 400 mg
    Reporting group description
    		 Part A cohort participants received BMS-986226 400 mg every 4 weeks for 24 weeks

    Reporting group title
    Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Reporting group description
    		 Part C1 cohort participants received BMS-986226 25 mg every 12 weeks plus Ipilimumab 3 mg/kg every 4 weeks

    Reporting group title
    Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg
    Reporting group description
    		 Part C1 cohort participants received BMS-986226 200 mg every 12 weeks plus Ipilimumab 3 mg/kg every 4 weeks

    Reporting group title
    Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg
    Reporting group description
    		 Part C2 cohort participants received BMS-986226 25 mg every 4 weeks plus Ipilimumab 3 mg/kg every 4 weeks

    Reporting group title
    Total
    Reporting group description
    		 Total treated participants

    Serious adverse events
    		 Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Preliminary - BMS-986226 2 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Total
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 7 (42.86%)
    2 / 7 (28.57%)
    10 / 11 (90.91%)
    5 / 9 (55.56%)
    2 / 6 (33.33%)
    9 / 9 (100.00%)
    5 / 10 (50.00%)
    9 / 12 (75.00%)
    5 / 9 (55.56%)
    50 / 80 (62.50%)
         number of deaths (all causes)
    3
    5
    8
    5
    5
    7
    7
    8
    5
    53
         number of deaths resulting from adverse events
    1
    1
    4
    4
    1
    6
    4
    7
    4
    32
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    5 / 11 (45.45%)
    4 / 9 (44.44%)
    1 / 6 (16.67%)
    6 / 9 (66.67%)
    5 / 10 (50.00%)
    6 / 12 (50.00%)
    4 / 9 (44.44%)
    33 / 80 (41.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 5
    0 / 4
    0 / 1
    0 / 6
    0 / 5
    0 / 6
    0 / 4
    0 / 33
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 4
    0 / 1
    0 / 6
    0 / 4
    0 / 5
    0 / 4
    0 / 29
    Tumour associated fever
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Vascular disorders
    Shock
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Assisted suicide
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Hallucination
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    2 / 80 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocarditis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    2 / 11 (18.18%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    4 / 80 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Large intestinal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    2 / 80 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Otitis media
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Preliminary - BMS-986226 8 mg Part A - BMS-986226 25 mg Part A - BMS-986226 80 mg Part A - BMS-986226 200 mg Preliminary - BMS-986226 2 mg Part A - BMS-986226 400 mg Part C1 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Part C1 - BMS-986226 200 mg + Ipilimumab 3 mg/kg Part C2 - BMS-986226 25 mg + Ipilimumab 3 mg/kg Total
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    7 / 7 (100.00%)
    10 / 11 (90.91%)
    9 / 9 (100.00%)
    6 / 6 (100.00%)
    9 / 9 (100.00%)
    10 / 10 (100.00%)
    12 / 12 (100.00%)
    9 / 9 (100.00%)
    79 / 80 (98.75%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    2
    Vascular disorders
    Flushing
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    2
    Hypertension
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    2 / 9 (22.22%)
    4 / 80 (5.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    2
    4
    Hot flush
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Hypotension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    2 / 9 (22.22%)
    4 / 80 (5.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    2
    4
    Fatigue
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    4 / 11 (36.36%)
    3 / 9 (33.33%)
    2 / 6 (33.33%)
    5 / 9 (55.56%)
    3 / 10 (30.00%)
    5 / 12 (41.67%)
    1 / 9 (11.11%)
    25 / 80 (31.25%)
         occurrences all number
    1
    1
    4
    3
    2
    6
    3
    5
    1
    26
    Malaise
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Mucosal inflammation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    2
    Oedema peripheral
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
    6 / 80 (7.50%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    1
    1
    1
    6
    Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    4 / 80 (5.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    0
    1
    4
    Pyrexia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    1 / 11 (9.09%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    3 / 9 (33.33%)
    2 / 10 (20.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    10 / 80 (12.50%)
         occurrences all number
    1
    1
    1
    1
    0
    4
    3
    1
    0
    12
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Oedema genital
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Vaginal discharge
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 7 (14.29%)
    1 / 11 (9.09%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    2 / 9 (22.22%)
    9 / 80 (11.25%)
         occurrences all number
    2
    1
    1
    1
    1
    0
    0
    1
    2
    9
    Dyspnoea
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    5 / 80 (6.25%)
         occurrences all number
    2
    1
    0
    0
    1
    0
    0
    1
    0
    5
    Haemoptysis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Dyspnoea exertional
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    2 / 80 (2.50%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    1
    2
    Nasal congestion
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Hiccups
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    2
    0
    3
    Rhinorrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    2
    Anxiety
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    0
    0
    2
    Hallucination
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    2
    Investigations
    Amylase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    5
    0
    7
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    2 / 11 (18.18%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    6 / 80 (7.50%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    2
    0
    2
    7
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 7 (0.00%)
    2 / 11 (18.18%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    4 / 10 (40.00%)
    3 / 12 (25.00%)
    1 / 9 (11.11%)
    15 / 80 (18.75%)
         occurrences all number
    3
    0
    2
    1
    1
    0
    4
    4
    2
    17
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    0
    3
    Blood bilirubin increased
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    3 / 11 (27.27%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    8 / 80 (10.00%)
         occurrences all number
    1
    1
    3
    0
    0
    0
    2
    1
    0
    8
    Blood creatinine increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    3 / 9 (33.33%)
    0 / 10 (0.00%)
    3 / 12 (25.00%)
    0 / 9 (0.00%)
    6 / 80 (7.50%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    4
    0
    7
    CD4 lymphocytes decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    2
    0
    3
    Lipase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    4 / 80 (5.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    4
    0
    7
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    3 / 80 (3.75%)
         occurrences all number
    0
    0
    0
    0
    0
    4
    0
    0
    1
    5
    Platelet count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    2
    Weight decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    2
    0
    3
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Clavicle fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Fall
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Infusion related reaction
         subjects affected / exposed
    3 / 7 (42.86%)
    3 / 7 (42.86%)
    5 / 11 (45.45%)
    8 / 9 (88.89%)
    0 / 6 (0.00%)
    8 / 9 (88.89%)
    4 / 10 (40.00%)
    6 / 12 (50.00%)
    3 / 9 (33.33%)
    40 / 80 (50.00%)
         occurrences all number
    3
    3
    6
    9
    0
    9
    5
    7
    4
    46
    Muscle strain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Procedural pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    2
    0
    3
    Subdural haematoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Sinus tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Tachycardia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Dizziness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
    3 / 80 (3.75%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    1
    3
    Dysaesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    2
    Lethargy
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Hypoaesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    2
    Headache
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    2 / 9 (22.22%)
    7 / 80 (8.75%)
         occurrences all number
    2
    0
    1
    0
    0
    0
    0
    4
    2
    9
    Neuralgia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    2
    Neuropathy peripheral
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    2
    Paraesthesia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Presyncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Tremor
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    3 / 11 (27.27%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    3 / 9 (33.33%)
    2 / 10 (20.00%)
    4 / 12 (33.33%)
    0 / 9 (0.00%)
    14 / 80 (17.50%)
         occurrences all number
    0
    0
    3
    1
    1
    3
    3
    4
    0
    15
    Eosinophilia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Lymphopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    2
    Thrombocytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    2
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Eye disorders
    Asthenopia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Periorbital oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    4 / 80 (5.00%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    0
    1
    0
    4
    Ascites
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    2
    Abdominal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    3 / 11 (27.27%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
    3 / 10 (30.00%)
    3 / 12 (25.00%)
    0 / 9 (0.00%)
    15 / 80 (18.75%)
         occurrences all number
    1
    1
    4
    2
    0
    2
    3
    3
    0
    16
    Constipation
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    3 / 12 (25.00%)
    2 / 9 (22.22%)
    10 / 80 (12.50%)
         occurrences all number
    1
    0
    1
    1
    1
    0
    1
    3
    2
    10
    Diarrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    3 / 11 (27.27%)
    0 / 9 (0.00%)
    2 / 6 (33.33%)
    4 / 9 (44.44%)
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    11 / 80 (13.75%)
         occurrences all number
    0
    0
    3
    0
    3
    4
    1
    1
    0
    12
    Dyspepsia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    2
    Flatulence
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Haematochezia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Inguinal hernia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Melaena
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Intestinal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    0
    0
    0
    3
    Nausea
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    6 / 9 (66.67%)
    3 / 10 (30.00%)
    3 / 12 (25.00%)
    0 / 9 (0.00%)
    16 / 80 (20.00%)
         occurrences all number
    2
    0
    1
    0
    1
    6
    3
    3
    0
    16
    Rectal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    2
    Stomatitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    2 / 80 (2.50%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    1
    2
    Vomiting
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    2 / 9 (22.22%)
    1 / 6 (16.67%)
    2 / 9 (22.22%)
    1 / 10 (10.00%)
    4 / 12 (33.33%)
    3 / 9 (33.33%)
    14 / 80 (17.50%)
         occurrences all number
    1
    0
    0
    2
    1
    2
    1
    4
    6
    17
    Hepatobiliary disorders
    Hepatobiliary disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    2
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    2
    Jaundice
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Portal hypertension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    2
    Dermatitis acneiform
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    3 / 80 (3.75%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    1
    3
    Erythema
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Hyperhidrosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    2 / 6 (33.33%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    4 / 12 (33.33%)
    1 / 9 (11.11%)
    9 / 80 (11.25%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    1
    4
    1
    9
    Nail disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Rash
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
    3 / 80 (3.75%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    1
    3
    Rash maculo-papular
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    3 / 12 (25.00%)
    0 / 9 (0.00%)
    6 / 80 (7.50%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    1
    5
    0
    8
    Urticaria
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Urinary tract obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Renal disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    2
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    1
    1
    0
    0
    0
    1
    0
    0
    0
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    1
    0
    3
    Back pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    0
    0
    3
    Bone pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Flank pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Myalgia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 11 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    2 / 9 (22.22%)
    5 / 80 (6.25%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    0
    2
    5
    Pain in jaw
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Neck pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Cystitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Fungal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Gastroenteritis viral
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Herpes zoster
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    1 / 9 (11.11%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    2
    Oral herpes
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    2 / 80 (2.50%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    1
    2
    Mucosal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    3 / 80 (3.75%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    1
    3
    Skin infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    2 / 12 (16.67%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    2
    0
    3
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Soft tissue infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    1 / 9 (11.11%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    2
    Vaginal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    2 / 11 (18.18%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    5 / 9 (55.56%)
    2 / 10 (20.00%)
    3 / 12 (25.00%)
    0 / 9 (0.00%)
    15 / 80 (18.75%)
         occurrences all number
    1
    1
    2
    0
    1
    5
    2
    3
    0
    15
    Dehydration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    2 / 11 (18.18%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    3 / 80 (3.75%)
         occurrences all number
    0
    0
    2
    0
    0
    1
    0
    0
    0
    3
    Hypercalcaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Hyperkalaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    5 / 80 (6.25%)
         occurrences all number
    1
    1
    2
    0
    1
    0
    0
    3
    0
    8
    Hypernatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    0
    0
    0
    3
    Hyperphosphataemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Hyperuricaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    1 / 80 (1.25%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Hypoglycaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    2
    Hypomagnesaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    1 / 12 (8.33%)
    0 / 9 (0.00%)
    4 / 80 (5.00%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    0
    1
    0
    5
    Hyponatraemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 12 (0.00%)
    0 / 9 (0.00%)
    2 / 80 (2.50%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Jul 2017
    Preliminary safety cohort added
    03 Apr 2018
    Combination escalation modification of BMS-986226 with either nivolumab (Part B) or ipilimumab (Part C) to include and prioritize a Q12W dosing schedule. On-treatment biopsy collections were changed to Q2W and Q12W. A tetanus booster will be administered to capture pharmacodynamic activity in an antigen-specific context. Treatment duration of BMS-986226 in combination with nivolumab or ipilimumab will be 2 years.
    02 Dec 2018
    The eligibility criteria was modified to include additional tumor types, including but not limited to Cervical Cancer (CC), Melanoma (MEL), Renal Cell Carcinoma (RCC) and Triple Negative Breast Cancer (TNBC). The eligibility criteria was modified to allow for up to three prior lines of systemic therapy. The requirement for ICOS expression confirmation by IHC in pretreatment biopsies prior to start of treatment was removed. The protocol was modified to require tetanus booster administration 3-7 days prior to first treatment. The protocol was modified to optimize sample collection for pharmacokinetic, pharmacodynamic and biomarker analysis. The option for retreatment was removed from the protocol.
    31 May 2019
    Fasting glucose testing was limited to the Screening Period; on treatment glucose testing can be non-fasting. Guidance for premedication was added.

    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.
    Study CA021002 was terminated because the Sponsor discontinued further development of BMS-986226. The decision for the study closure was not related to any safety concerns associated with BMS-986226.
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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