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    Clinical Trial Results:
    A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients with Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia

    Summary
    EudraCT number
    2010-020414-28
    Trial protocol
    GB   SE   DE   FR   BE   NL   ES   IT  
    Global end of trial date
    17 Jan 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    02 Feb 2020
    First version publication date
    02 Feb 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    AP24534-10-201
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01207440
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    40 Landsdowne Street, Cambridge, MA, United States, 02139
    Public contact
    Medical Director, Clinical Science, Takeda, +1 877-825-3327, clinicaltrialregistry@tpna.com
    Scientific contact
    Medical Director, Clinical Science, Takeda, +1 877-825-3327, clinicaltrialregistry@tpna.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
    17 Jan 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Jan 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study is to determine the efficacy of ponatinib in participants with chronic myeloid leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast phase (BP) or with philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who either are resistant or intolerant to either dasatinib or nilotinib, or have the (T)hreonine-315-(I)soleucine (T315I) mutation.
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    30 Sep 2010
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    96 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 12
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    Canada: 17
    Country: Number of subjects enrolled
    France: 55
    Country: Number of subjects enrolled
    Germany: 37
    Country: Number of subjects enrolled
    Italy: 39
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Korea, Republic of: 27
    Country: Number of subjects enrolled
    Singapore: 17
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    Sweden: 6
    Country: Number of subjects enrolled
    United Kingdom: 29
    Country: Number of subjects enrolled
    United States: 189
    Worldwide total number of subjects
    449
    EEA total number of subjects
    187
    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)
    294
    From 65 to 84 years
    150
    85 years and over
    5

    Subject disposition

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    Recruitment
    Recruitment details
    Participants took part in the study at 66 investigative sites in the Australia, Belgium, Canada, France, Germany, Italy, the Netherlands, Republic of Korea, Singapore, Spain, Sweden, the United Kingdom and the United States from 30 September 2010 to 17 January 2019.

    Pre-assignment
    Screening details
    Participants were assigned to 1 of 6 cohorts: chronic myeloid leukemia (CML) in chronic (CP), accelerated (AP), or blast phase (BP), or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) who were resistant or intolerant (R-I) to either dasatinib or nilotinib or had (T)hreonine-315-(I)soleucine (T315I) mutation.

    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
    Cohort A: CP-CML R-I
    Arm description
    CP-CML participants R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).
    Arm type
    Experimental

    Investigational medicinal product name
    Ponatinib
    Investigational medicinal product code
    Other name
    AP24534 Iclusig
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ponatinib tablets.

    Arm title
    Cohort B: CP-CML with T315I Mutation
    Arm description
    CP-CML participants who had T315I mutation of breakpoint cluster region-Abelson complex (BCR-ABL) were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).
    Arm type
    Experimental

    Investigational medicinal product name
    Ponatinib
    Investigational medicinal product code
    Other name
    AP24534 Iclusig
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ponatinib tablets.

    Arm title
    Cohort C: AP-CML R-I
    Arm description
    AP-CML R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).
    Arm type
    Experimental

    Investigational medicinal product name
    Ponatinib
    Investigational medicinal product code
    Other name
    AP24534 Iclusig
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ponatinib tablets.

    Arm title
    Cohort D: AP-CML with T315I Mutation
    Arm description
    AP-CML participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).
    Arm type
    Experimental

    Investigational medicinal product name
    Ponatinib
    Investigational medicinal product code
    Other name
    AP24534 Iclusig
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ponatinib tablets.

    Arm title
    Cohort E: BP-CML/Ph+ ALL R-I
    Arm description
    BP-CML or Ph+ ALL R-I to dasatinib or nilotinib or Ph+ ALL R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).
    Arm type
    Experimental

    Investigational medicinal product name
    Ponatinib
    Investigational medicinal product code
    Other name
    AP24534 Iclusig
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ponatinib tablets.

    Arm title
    Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Arm description
    BP-CML or Ph+ ALL participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).
    Arm type
    Experimental

    Investigational medicinal product name
    Ponatinib
    Investigational medicinal product code
    Other name
    AP24534 Iclusig
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ponatinib tablets.

    Arm title
    Unassigned to Cohorts A-F
    Arm description
    Participants who were not assigned to any of the cohorts and have no T315I mutation at study entry and were not resistant or intolerant to dasatinib or nilotinib, administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).
    Arm type
    Experimental

    Investigational medicinal product name
    Ponatinib
    Investigational medicinal product code
    Other name
    AP24534 Iclusig
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ponatinib tablets.

    Number of subjects in period 1
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation Unassigned to Cohorts A-F
    Started
    203
    64
    65
    18
    48
    46
    5
    Completed
    0
    0
    0
    0
    0
    0
    0
    Not completed
    203
    64
    65
    18
    48
    46
    5
         Protocol deviation
    2
    -
    -
    -
    -
    -
    -
         Physician decision
    6
    5
    5
    -
    1
    -
    -
         Terminated by Sponsor
    69
    19
    12
    2
    3
    -
    2
         Non-compliance with Study Drug
    3
    -
    1
    -
    -
    -
    -
         Lack of efficacy
    13
    2
    5
    1
    2
    3
    -
         Reason Not Specified
    10
    10
    7
    -
    4
    3
    -
         Adverse event, serious fatal
    6
    3
    2
    2
    7
    5
    1
         Adverse event, non-fatal
    46
    11
    7
    2
    6
    6
    2
         Progressive Disease
    19
    10
    19
    7
    23
    27
    -
         Consent withdrawn by subject
    29
    4
    5
    3
    2
    2
    -
         Lost to follow-up
    -
    -
    2
    1
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort A: CP-CML R-I
    Reporting group description
    CP-CML participants R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort B: CP-CML with T315I Mutation
    Reporting group description
    CP-CML participants who had T315I mutation of breakpoint cluster region-Abelson complex (BCR-ABL) were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort C: AP-CML R-I
    Reporting group description
    AP-CML R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort D: AP-CML with T315I Mutation
    Reporting group description
    AP-CML participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort E: BP-CML/Ph+ ALL R-I
    Reporting group description
    BP-CML or Ph+ ALL R-I to dasatinib or nilotinib or Ph+ ALL R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Reporting group description
    BP-CML or Ph+ ALL participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Unassigned to Cohorts A-F
    Reporting group description
    Participants who were not assigned to any of the cohorts and have no T315I mutation at study entry and were not resistant or intolerant to dasatinib or nilotinib, administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group values
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation Unassigned to Cohorts A-F Total
    Number of subjects
    203 64 65 18 48 46 5 449
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        median (full range (min-max))
    61.0 (22 to 94) 52.0 (18 to 87) 60.0 (23 to 82) 54.0 (24 to 78) 54.0 (18 to 74) 56.0 (18 to 80) 63.0 (51 to 71) -
    Sex: Female, Male
    Units: Subjects
        Female
    108 16 40 7 17 20 3 211
        Male
    95 48 25 11 31 26 2 238
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian/Alaska native
    1 0 1 0 0 0 0 2
        Asian
    17 14 8 3 8 7 2 59
        Black/African American
    7 4 7 5 1 1 0 25
        White
    174 42 47 9 39 38 3 352
        Unknown
    3 3 2 0 0 0 0 8
        Other
    1 1 0 1 0 0 0 3
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    13 8 6 1 2 12 0 42
        Not Hispanic or Latino
    190 56 59 17 46 34 5 407
        Unknown or Not Reported
    0 0 0 0 0 0 0 0
    Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
    ECOG-PS measured on-therapy assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hrs), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead.
    Units: Subjects
        ECOG=0
    139 47 33 12 15 16 5 267
        ECOG=1
    60 17 25 6 20 19 0 147
        ECOG=2
    4 0 7 0 12 11 0 34
        Missing ECOG Data
    0 0 0 0 1 0 0 1
    Time From Diagnosis to First Dose
    Units: years
        median (full range (min-max))
    7.85 (0.45 to 27.43) 4.78 (1.16 to 19.49) 7.13 (0.33 to 28.47) 6.61 (1.17 to 15.90) 3.96 (0.62 to 27.21) 1.63 (0.46 to 14.14) 4.80 (1.74 to 18.60) -

    End points

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    End points reporting groups
    Reporting group title
    Cohort A: CP-CML R-I
    Reporting group description
    CP-CML participants R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort B: CP-CML with T315I Mutation
    Reporting group description
    CP-CML participants who had T315I mutation of breakpoint cluster region-Abelson complex (BCR-ABL) were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort C: AP-CML R-I
    Reporting group description
    AP-CML R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort D: AP-CML with T315I Mutation
    Reporting group description
    AP-CML participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort E: BP-CML/Ph+ ALL R-I
    Reporting group description
    BP-CML or Ph+ ALL R-I to dasatinib or nilotinib or Ph+ ALL R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Reporting group description
    BP-CML or Ph+ ALL participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Unassigned to Cohorts A-F
    Reporting group description
    Participants who were not assigned to any of the cohorts and have no T315I mutation at study entry and were not resistant or intolerant to dasatinib or nilotinib, administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Primary: Percentage of CP-CML Participants with Major Cytogenetic Response (MCyR)

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    End point title
    Percentage of CP-CML Participants with Major Cytogenetic Response (MCyR) [1] [2]
    End point description
    MCyR is defined as percentage of participants with complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Cytogenetic response is the percentage of Philadelphia chromosome positive (Ph+) metaphases in bone marrow (BM). Response is further defined as MCyR: CCyR or PCyR, where CCyR: no Ph+ cells; PCyR: 1 to 35% Ph+ cells. Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts A and B only.
    End point type
    Primary
    End point timeframe
    Up to 12 months after initiation of study treatment
    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: This endpoint was analyzed only in Cohorts C and D.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in Cohorts A and B.
    End point values
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation
    Number of subjects analysed
    203
    64
    Units: percentage of participants
        number (confidence interval 95%)
    50.7 (43.6 to 57.8)
    70.3 (57.6 to 81.1)
    No statistical analyses for this end point

    Primary: Percentage of AP-CML Participants with Major Hematologic Response (MaHR)

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    End point title
    Percentage of AP-CML Participants with Major Hematologic Response (MaHR) [3] [4]
    End point description
    MaHR is defined as percentage of participants with complete hematologic response (CHR) or no evidence of leukemia(NEL). Response criteria for CHR is reported as white blood cells(WBC)≤institutional upper limit of normal (ULN), absolute neutrophil count (ANC)≥1000/mm^3, platelets≥100,000/mm^3, no blasts or promyelocytes in peripheral blood,BM blasts ≤5%,<5% myelocytes plus metamyelocytes in peripheral blood,basophils in peripheral blood <5%,no extramedullary involvement;Response criteria for NEL is reported as WBC≤institutional ULN,no blasts or promyelocytes in peripheral blood,BM blasts ≤5%,<5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <5%,no extramedullary involvement,at least 1 of the following:(i)20,000/mm^3≤platelets<100,000/mm^3;(ii)500/mm^3≤ANC<1000/mm^3.Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib.The data for this outcome measure is applicable for Cohorts C and D only.
    End point type
    Primary
    End point timeframe
    Up to 6 months after initiation of study treatment
    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: This endpoint was analyzed only in Cohorts C and D.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in Cohorts c and D.
    End point values
    Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation
    Number of subjects analysed
    65
    18
    Units: percentage of participants
        number (confidence interval 95%)
    56.9 (44.0 to 69.2)
    55.6 (30.8 to 78.5)
    No statistical analyses for this end point

    Primary: Percentage of BP-CML/Ph+ ALL Participants with MaHR

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    End point title
    Percentage of BP-CML/Ph+ ALL Participants with MaHR [5] [6]
    End point description
    MaHR is defined as percentage of participants with CHR or NEL. Response criteria for CHR is reported as WBC≤institutional upper limit of normal, ANC≥1000/mm^3, platelets ≥100,000/mm^3, no blasts or promyelocytes in peripheral blood, BM blasts ≤5%, <5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <5%, no extramedullary involvement; Response criteria for NEL is reported as WBC≤ institutional upper limit of normal, no blasts or promyelocytes in peripheral blood, BM blasts ≤5%, <5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <5%, no extramedullary involvement, at least 1 of the following: (i) 20,000/mm^3 ≤platelets<100,000/mm^3; (ii) 500/mm^3≤ANC<1000/mm^3. Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts E and F only.
    End point type
    Primary
    End point timeframe
    Up to 6 months after initiation of study treatment
    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: This endpoint was analyzed only in Cohorts E and F.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in Cohorts E and F.
    End point values
    Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Number of subjects analysed
    48
    46
    Units: percentage of participants
        number (confidence interval 95%)
    35.4 (22.2 to 50.5)
    32.6 (19.5 to 48.0)
    No statistical analyses for this end point

    Secondary: Percentage of CP-CML Participants with CHR

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    End point title
    Percentage of CP-CML Participants with CHR [7]
    End point description
    Response criteria for CHR is reported as WBC≤institutional upper limit of normal, platelets<450,000/mm^3, no blasts or promyelocytes in peripheral blood, <5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <5%, no extramedullary involvement (including no hepatomegaly or splenomegaly). Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts A and B only.
    End point type
    Secondary
    End point timeframe
    Every 3 cycles up to 39 cycles, followed by every subsequent sixth cycle (Up to approximately 48 months after first dose)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in Cohorts A and B.
    End point values
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation
    Number of subjects analysed
    203
    64
    Units: percentage of participants
        number (confidence interval 95%)
    94.6 (90.5 to 97.3)
    92.2 (82.7 to 97.4)
    No statistical analyses for this end point

    Secondary: Percentage of CP-CML Participants with Confirmed MCyR

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    End point title
    Percentage of CP-CML Participants with Confirmed MCyR [8]
    End point description
    Confirmed MCyR is defined as 2 assessments of CCyR or PCyR at least 28 days apart. For CP participants entering the trial in PCyR, confirmed MCyR is defined as 2 assessments of CCyR at least 28 days apart. Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts A and B only.
    End point type
    Secondary
    End point timeframe
    Every 3 cycles up to 39 cycles, followed by every subsequent sixth cycle (Up to approximately 48 months after first dose)
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in Cohorts A and B.
    End point values
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation
    Number of subjects analysed
    203
    64
    Units: percentage of participants
        number (confidence interval 95%)
    40.9 (34.1 to 48.0)
    62.5 (49.5 to 74.3)
    No statistical analyses for this end point

    Secondary: Percentage of CP-CML Participants with Major Molecular Response (MMR)

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    End point title
    Percentage of CP-CML Participants with Major Molecular Response (MMR) [9]
    End point description
    MMR is defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL ≤0.1% on the international scale (equivalent to a 3-log reduction in transcript). Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts A and B only.
    End point type
    Secondary
    End point timeframe
    Every 3 cycles up to 39 cycles, followed by every subsequent sixth cycle (Up to approximately 48 months after first dose)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in Cohorts A and B.
    End point values
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation
    Number of subjects analysed
    203
    64
    Units: percentage of participants
        number (confidence interval 95%)
    35.0 (28.4 to 42.0)
    57.8 (44.8 to 70.1)
    No statistical analyses for this end point

    Secondary: Percentage of AP-CML or BP-CML/Ph+ ALL Participants with MCyR

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    End point title
    Percentage of AP-CML or BP-CML/Ph+ ALL Participants with MCyR [10]
    End point description
    MCyR is defined as percentage of participants with CCyR or PCyR. Cytogenetic response is the percentage of Ph+ metaphases in BM. Response is further defined as MCyR: CCyR or PCyR, where CCyR: no Ph+ cells; PCyR: 1 to 35% Ph+ cells. Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts C to F only.
    End point type
    Secondary
    End point timeframe
    Every 2 cycles up to 26 cycles, followed by every 3 cycles from cycles 27 through 39, and then every subsequent sixth cycle (Up to approximately 48 months after first dose)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in Cohorts C, D, E and F.
    End point values
    Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Number of subjects analysed
    65
    18
    48
    46
    Units: percentage of participants
        number (confidence interval 95%)
    33.8 (22.6 to 46.6)
    55.6 (30.8 to 78.5)
    27.1 (15.3 to 41.8)
    34.8 (21.4 to 50.2)
    No statistical analyses for this end point

    Secondary: Percentage of AP-CML or BP-CML/Ph+ ALL Participants with Confirmed MCyR

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    End point title
    Percentage of AP-CML or BP-CML/Ph+ ALL Participants with Confirmed MCyR [11]
    End point description
    Confirmed MCyR is defined as 2 assessments of CCyR or PCyR at least 28 days apart. Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts C to F only.
    End point type
    Secondary
    End point timeframe
    Every 2 cycles up to 26 cycles, followed by every 3 cycles from cycles 27 through 39, and then every subsequent sixth cycle (Up to approximately 48 months after first dose)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in Cohorts C, D, E and F.
    End point values
    Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Number of subjects analysed
    65
    18
    48
    46
    Units: percentage of participants
        number (confidence interval 95%)
    24.6 (14.8 to 36.9)
    38.9 (17.3 to 64.3)
    20.8 (10.5 to 35.0)
    15.2 (6.3 to 28.9)
    No statistical analyses for this end point

    Secondary: Percentage of AP-CML or BP-CML/Ph+ ALL Participants with MMR

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    End point title
    Percentage of AP-CML or BP-CML/Ph+ ALL Participants with MMR [12]
    End point description
    MMR is defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL ≤0.1% on the international scale (equivalent to a 3-log reduction in transcript). Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts C to F only.
    End point type
    Secondary
    End point timeframe
    Every 2 cycles up to 26 cycles, followed by every 3 cycles from cycles 27 through 39, and then every subsequent sixth cycle (Up to approximately 48 months after first dose)
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in Cohorts E and F.
    End point values
    Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Number of subjects analysed
    65
    18
    48
    46
    Units: percentage of participants
        number (confidence interval 95%)
    18.5 (9.9 to 30.0)
    33.3 (13.3 to 59.0)
    18.8 (8.9 to 32.6)
    4.3 (0.5 to 14.8)
    No statistical analyses for this end point

    Secondary: Time to Response

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    End point title
    Time to Response [13]
    End point description
    Time to response is defined as the interval from the first dose of study treatment until the criteria for response are first met, censored at the last assessment of response. Median time to response was estimated using the Kaplan-Meier method. Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. Median time to response was reported for responders only. Participants who did not achieve the specified response were censored at the last response assessment. Number analysed: participants with data available at given time-point.
    End point type
    Secondary
    End point timeframe
    Up to approximately 48 months after first dose
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in all Cohorts except the unassigned cohorts.
    End point values
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Number of subjects analysed
    203
    64
    65
    18
    48
    46
    Units: days
    median (full range (min-max))
        Hematologic Response (n= 192, 59, 37, 10, 17, 15)
    13.0 (1 to 417)
    10.0 (4 to 1008)
    21.0 (12 to 112)
    20.5 (14 to 176)
    28.0 (14 to 168)
    24.0 (11 to 57)
        Cytogenetic Response (n= 103, 45, 22, 10, 13, 16)
    85.0 (56 to 343)
    84.0 (49 to 333)
    113.5 (26 to 280)
    83.0 (25 to 295)
    28.0 (28 to 168)
    56.0 (27 to 112)
        Molecular Response (n= 71, 37, 12, 6, 9, 2)
    173.0 (55 to 1686)
    167.0 (81 to 756)
    340.5 (55 to 1364)
    335.5 (107 to 925)
    56.0 (54 to 113)
    63.0 (59 to 67)
    No statistical analyses for this end point

    Secondary: Duration of Response

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    End point title
    Duration of Response [14]
    End point description
    Duration of Response is defined as the interval between the first assessment at which the criteria for response are met until the criteria for progression are met, censored at the last date at which the criteria for response are met. Duration of response was estimated by the Kaplan-Meier method as the probability of remaining in response. Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. Number analysed is number of participants with data available for analysis at given time-point. 9999 indicates duration of response was not reached for Cohorts A and B due to fewer number of participants with events. 99999 indicates duration of response was not reached due to fewer number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to approximately 48 months after first dose
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in all Cohorts except the unassigned cohorts.
    End point values
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Number of subjects analysed
    203
    64
    65
    18
    48
    46
    Units: days
    median (full range (min-max))
        Hematologic Response (n= 192, 59, 37, 10, 17, 15)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    360.0 (35 to 2079)
    732.0 (42 to 1334)
    196.0 (54 to 1811)
    108.0 (54 to 1038)
        Cytogenetic Response (n= 103, 45, 22, 10, 13, 16)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    99999 (99999 to 99999)
    728.0 (28 to 1569)
    99999 (99999 to 99999)
    63.0 (1 to 673)
        Molecular Response (n= 71, 37, 12, 6, 9, 2)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    560.0 (1 to 1666)
    222.0 (1 to 783)
    99999 (99999 to 99999)
    98.0 (1 to 98)
    No statistical analyses for this end point

    Secondary: Progression-free Survival (PFS)

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    End point title
    Progression-free Survival (PFS) [15]
    End point description
    PFS is interval from first dose of study drug until criteria for progression or death are met,censored at last response assessment.Progression from CP reported as death,development of AP or BP,loss of CHR (in absence of cytogenetic response),confirmed by development in complete blood counts(CBCs) >=4weeks apart,loss of MCyR,increasing WBC in participant without CHR defined by doubling of WBC to >20K on 2 occasions >=4weeks apart;Progression from AP reported as death,development of confirmed BP,loss of previous major or minor hematologic response over a 2-week period,no decrease from baseline levels in percentage blasts in peripheral blood or BM on all assessments over a 4-week period;Progression from BP or Ph+ ALL reported as death, increasing blasts in peripheral blood or BM over a 4 week period.Treated population:participants assigned to Cohorts A to F who received >=1 dose of ponatinib.999999:PFS was not reached for Cohorts A and B due to fewer number of participants with events.
    End point type
    Secondary
    End point timeframe
    Every 12 weeks ± 2 weeks from last dose of study drug or the investigator/participant decision to discontinue treatment, whichever occurred later (Up to approximately 96 months after last dose)
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in all Cohorts except the unassigned cohorts.
    End point values
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Number of subjects analysed
    203
    64
    65
    18
    48
    46
    Units: days
        median (confidence interval 95%)
    999999 (1285.0 to 999999)
    1809.0 (1028.0 to 999999)
    432.0 (335.0 to 714.0)
    959.0 (186.0 to 1847.0)
    111.0 (55.0 to 169.0)
    83.0 (55.0 to 150.0)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    Overall Survival (OS) [16]
    End point description
    OS is defined as the interval from the first dose of study treatment until death, censored at the last date at which participant was known to be alive. Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. 9999999 indicates median OS has not been reached for Cohort A and B due to fewer number of participants with events. 99999999 indicates uper limit of 95% confidence interval was not estimable due to fewer number of participants with events.
    End point type
    Secondary
    End point timeframe
    From the first dose of study treatment until death (Up to 96 months post last dose)
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was analyzed only in all Cohorts except the unassigned cohorts.
    End point values
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Number of subjects analysed
    203
    64
    65
    18
    48
    46
    Units: days
        median (confidence interval 95%)
    9999999 (9999999 to 9999999)
    9999999 (9999999 to 9999999)
    1689.0 (969.0 to 99999999)
    1847.0 (281.0 to 2143.0)
    209.0 (119.0 to 379.0)
    200.0 (150.0 to 279.0)
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment-Emergent Adverse Event (TEAE) and Serious AE (SAE)

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    End point title
    Number of Participants with Treatment-Emergent Adverse Event (TEAE) and Serious AE (SAE)
    End point description
    AE is any untoward medical occurrence in a participant administered medicinal investigational drug.Untoward medical occurrence does not necessarily have to have causal relationship with treatment.SAE is any untoward medical occurrence that results in death;is life-threatening;requires inpatient hospitalization or prolongation of present hospitalization;results in persistent or significant disability/incapacity;is congenital anomaly/birth defect or is medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above,or involves suspected transmission via medicinal product of infectious agent.TEAE:an AE that occurs after administration of first dose and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.Safety population:participants who received >=1 dose of ponatinib.
    End point type
    Secondary
    End point timeframe
    From first dose up to 30 days after last dose of the study drug (Up to approximately 49 months)
    End point values
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation Unassigned to Cohorts A-F
    Number of subjects analysed
    203
    64
    65
    18
    48
    46
    5
    Units: participants
        TEAE
    203
    64
    65
    18
    48
    46
    5
        SAE
    132
    39
    44
    13
    41
    37
    3
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs and Other AEs: From first dose up to 30 days after last dose of the study drug (Up to approximately 49 months); All-Cause Mortality: Up to approximately 8 years
    Adverse event reporting additional description
    At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Cohort A: CP-CML R-I
    Reporting group description
    CP-CML participants R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort B: CP-CML with T315I Mutation
    Reporting group description
    CP-CML participants who had T315I mutation of breakpoint cluster region-Abelson complex (BCR-ABL) were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort C: AP-CML R-I
    Reporting group description
    AP-CML R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort D: AP-CML with T315I Mutation
    Reporting group description
    AP-CML participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort E: BP-CML/Ph+ ALL R-I
    Reporting group description
    BP-CML or Ph+ ALL R-I to dasatinib or nilotinib or Ph+ ALL R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Cohort F: BP-CML or Ph+ ALL with T315I Mutation
    Reporting group description
    BP-CML or Ph+ ALL participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Reporting group title
    Unassigned AP/CP-CML
    Reporting group description
    Participants who were not assigned to any of the cohorts and have no T315I mutation at study entry and were not R-I to dasatinib or nilotinib, administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

    Serious adverse events
    Cohort A: CP-CML R-I Cohort B: CP-CML with T315I Mutation Cohort C: AP-CML R-I Cohort D: AP-CML with T315I Mutation Cohort E: BP-CML/Ph+ ALL R-I Cohort F: BP-CML or Ph+ ALL with T315I Mutation Unassigned AP/CP-CML
    Total subjects affected by serious adverse events
         subjects affected / exposed
    132 / 203 (65.02%)
    39 / 64 (60.94%)
    44 / 65 (67.69%)
    13 / 18 (72.22%)
    41 / 48 (85.42%)
    37 / 46 (80.43%)
    3 / 5 (60.00%)
         number of deaths (all causes)
    11
    5
    5
    5
    20
    14
    2
         number of deaths resulting from adverse events
    2
    0
    0
    1
    2
    1
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    11 / 203 (5.42%)
    0 / 64 (0.00%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    8 / 13
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    2 / 203 (0.99%)
    1 / 64 (1.56%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    4 / 203 (1.97%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hot flush
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    3 / 203 (1.48%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism venous
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    10 / 203 (4.93%)
    4 / 64 (6.25%)
    1 / 65 (1.54%)
    1 / 18 (5.56%)
    1 / 48 (2.08%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    8 / 10
    4 / 5
    0 / 1
    1 / 2
    1 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    4 / 203 (1.97%)
    3 / 64 (4.69%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    3 / 6
    2 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    4 / 203 (1.97%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    1 / 18 (5.56%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    3 / 6
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    2 / 203 (0.99%)
    1 / 64 (1.56%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dry gangrene
         subjects affected / exposed
    1 / 203 (0.49%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic arteriosclerosis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Temporal arteritis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coeliac artery occlusion
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism arterial
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm progression
         subjects affected / exposed
    6 / 203 (2.96%)
    2 / 64 (3.13%)
    7 / 65 (10.77%)
    4 / 18 (22.22%)
    14 / 48 (29.17%)
    8 / 46 (17.39%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    0 / 7
    0 / 4
    0 / 14
    0 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    0 / 2
    0 / 2
    0 / 10
    0 / 5
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    3 / 203 (1.48%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    2 / 203 (0.99%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant pleural effusion
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blast crisis in myelogenous leukaemia
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    1 / 18 (5.56%)
    1 / 48 (2.08%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    3 / 203 (1.48%)
    0 / 64 (0.00%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chloroma
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin squamous cell carcinoma metastatic
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large cell lung cancer recurrent
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-hodgkin's lymphoma
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vulval cancer
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Central nervous system leukaemia
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    1 / 18 (5.56%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Acute lymphocytic leukaemia recurrent
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine carcinoma metastatic
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bowen's disease
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Graft versus host disease in skin
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaphylactoid reaction
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    Immobile
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    5 / 203 (2.46%)
    3 / 64 (4.69%)
    5 / 65 (7.69%)
    2 / 18 (11.11%)
    2 / 48 (4.17%)
    2 / 46 (4.35%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    1 / 5
    2 / 3
    0 / 5
    0 / 2
    1 / 2
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    4 / 203 (1.97%)
    1 / 64 (1.56%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    1 / 18 (5.56%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    2 / 48 (4.17%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 203 (0.49%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 203 (0.00%)
    2 / 64 (3.13%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Implant site pain
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular stent occlusion
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    3 / 203 (1.48%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    2 / 46 (4.35%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatic obstruction
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic ovarian cyst
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripancreatic fluid collection
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural vomiting
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    1 / 18 (5.56%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    1 / 18 (5.56%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonitis chemical
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery restenosis
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal column injury
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Lipase increased
         subjects affected / exposed
    4 / 203 (1.97%)
    3 / 64 (4.69%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    3 / 3
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 203 (1.48%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    2 / 48 (4.17%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urine analysis abnormal
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood potassium increased
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    JC polyomavirus test positive
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    11 / 203 (5.42%)
    4 / 64 (6.25%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    3 / 48 (6.25%)
    2 / 46 (4.35%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    9 / 21
    0 / 4
    0 / 0
    0 / 0
    1 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    5 / 203 (2.46%)
    3 / 64 (4.69%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    4 / 5
    2 / 4
    1 / 2
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    4 / 203 (1.97%)
    6 / 64 (9.38%)
    1 / 65 (1.54%)
    1 / 18 (5.56%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    5 / 7
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    2 / 203 (0.99%)
    1 / 64 (1.56%)
    1 / 65 (1.54%)
    2 / 18 (11.11%)
    2 / 48 (4.17%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 5
    1 / 2
    1 / 1
    1 / 2
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    10 / 203 (4.93%)
    4 / 64 (6.25%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    8 / 13
    3 / 5
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 203 (0.99%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    3 / 203 (1.48%)
    1 / 64 (1.56%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    3 / 203 (1.48%)
    3 / 64 (4.69%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 3
    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
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    1 / 18 (5.56%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    1 / 18 (5.56%)
    3 / 48 (6.25%)
    0 / 46 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    1 / 3
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    2 / 203 (0.99%)
    1 / 64 (1.56%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia supraventricular
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriospasm coronary
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac Discomfort
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dressler's syndrome
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bundle branch block right
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    3 / 203 (1.48%)
    4 / 64 (6.25%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    3 / 5
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 203 (3.45%)
    0 / 64 (0.00%)
    4 / 65 (6.15%)
    0 / 18 (0.00%)
    2 / 48 (4.17%)
    2 / 46 (4.35%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 9
    0 / 0
    1 / 4
    0 / 0
    1 / 3
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    1 / 18 (5.56%)
    5 / 48 (10.42%)
    5 / 46 (10.87%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
    1 / 1
    1 / 6
    1 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    1 / 18 (5.56%)
    2 / 48 (4.17%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    1 / 1
    1 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperviscosity syndrome
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Hyperleukocytosis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    2 / 46 (4.35%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 203 (0.49%)
    1 / 64 (1.56%)
    4 / 65 (6.15%)
    0 / 18 (0.00%)
    2 / 48 (4.17%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 203 (0.99%)
    3 / 64 (4.69%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 3
    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
    Hypoxia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 203 (1.48%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    3 / 48 (6.25%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 203 (0.99%)
    1 / 64 (1.56%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    1 / 46 (2.17%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 1
    0 / 0
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    2 / 46 (4.35%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    5 / 203 (2.46%)
    4 / 64 (6.25%)
    1 / 65 (1.54%)
    1 / 18 (5.56%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 7
    1 / 4
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    1 / 18 (5.56%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    2 / 203 (0.99%)
    2 / 64 (3.13%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral artery stenosis
         subjects affected / exposed
    0 / 203 (0.00%)
    2 / 64 (3.13%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    5 / 203 (2.46%)
    3 / 64 (4.69%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    4 / 5
    3 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic cerebral infarction
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic transformation stroke
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IVth nerve paralysis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    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
    Syncope
         subjects affected / exposed
    3 / 203 (1.48%)
    1 / 64 (1.56%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    1 / 18 (5.56%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial Paralysis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IIIrd nerve paralysis
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    5 / 203 (2.46%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 5
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular disorder
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Memory impairment
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal vein occlusion
         subjects affected / exposed
    2 / 203 (0.99%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystoid macular oedema
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal artery occlusion
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal vein thrombosis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    1 / 18 (5.56%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulcerative keratitis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Macular fibrosis
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis
         subjects affected / exposed
    10 / 203 (4.93%)
    4 / 64 (6.25%)
    3 / 65 (4.62%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    9 / 10
    4 / 5
    3 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    7 / 203 (3.45%)
    1 / 64 (1.56%)
    4 / 65 (6.15%)
    1 / 18 (5.56%)
    4 / 48 (8.33%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    6 / 9
    1 / 1
    0 / 4
    0 / 1
    1 / 5
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 203 (1.48%)
    1 / 64 (1.56%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 203 (0.49%)
    1 / 64 (1.56%)
    1 / 65 (1.54%)
    1 / 18 (5.56%)
    1 / 48 (2.08%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 1
    1 / 1
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 64 (1.56%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    2 / 48 (4.17%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 203 (0.99%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    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
    Ascites
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    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
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    2 / 65 (3.08%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    1 / 65 (1.54%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    2 / 46 (4.35%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Abdominal distension
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute abdomen
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    1 / 48 (2.08%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    1 / 46 (2.17%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis Noninfective
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis Ischaemic
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    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
    Fistula of small intestine
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 64 (0.00%)
    0 / 65 (0.00%)
    0 / 18 (0.00%)
    0 / 48 (0.00%)
    0 / 46 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0