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    Clinical Trial Results:
    A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 in Adults with Refractory Aggressive Non-Hodgkin Lymphoma

    Summary
    EudraCT number
    2015-005007-86
    Trial protocol
    NL   DE   FR  
    Global end of trial date
    27 Jul 2023

    Results information
    Results version number
    v1(current)
    This version publication date
    23 Jun 2024
    First version publication date
    23 Jun 2024
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    KTE-C19-101
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02348216
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Gilead Sciences
    Sponsor organisation address
    333 Lakeside Drive, Foster City, CA, United States, 94404
    Public contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Scientific contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.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
    27 Jul 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Jul 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Jul 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study was separated into 3 distinct phases designated as the Phase 1 study, Phase 2 pivotal study (Cohort 1 and Cohort 2), and Phase 2 safety management study (Cohort 3 and Cohort 4, Cohort 5 and Cohort 6). The primary objectives of this study were: - Phase 1 Study: Evaluate the safety of axicabtagene ciloleucel regimens - Phase 2 Pivotal Study; Evaluate the efficacy of axicabtagene ciloleucel - Phase 2 Safety Management Study: Assess the impact of prophylactic regimens or earlier interventions on the rate and severity of cytokine release syndrome (CRS) and neurologic toxicities Subjects who received an infusion of KTE-C19 completed the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968.
    Protection of trial subjects
    The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    21 Apr 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 25
    Country: Number of subjects enrolled
    France: 32
    Country: Number of subjects enrolled
    Germany: 24
    Country: Number of subjects enrolled
    Israel: 6
    Country: Number of subjects enrolled
    Netherlands: 42
    Country: Number of subjects enrolled
    United States: 178
    Worldwide total number of subjects
    307
    EEA total number of subjects
    98
    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)
    215
    From 65 to 84 years
    91
    85 years and over
    1

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Participants were enrolled at study sites in Canada, France, Germany, Israel, Netherlands, and the United States.

    Pre-assignment
    Screening details
    390 participants were screened. Participants who initially responded and subsequently relapsed, became eligible for second course of conditioning chemotherapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose.

    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
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot
    Arm description
    Participants with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) received conditioning chemotherapy (fludarabine 30 mg/m^2 intravenously [IV] over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of body weight (BW) on Day 0.
    Arm type
    Experimental

    Investigational medicinal product name
    Axicabtagene Ciloleucel
    Investigational medicinal product code
    Other name
    Yescarta®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Arm title
    Phase 2 (Pivotal Study): Cohort 1
    Arm description
    Participants with refractory DLBCL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.
    Arm type
    Experimental

    Investigational medicinal product name
    Axicabtagene Ciloleucel
    Investigational medicinal product code
    Other name
    Yescarta®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Arm title
    Phase 2 (Pivotal Study): Cohort 2
    Arm description
    Participants with refractory PMBCL or TFL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.
    Arm type
    Experimental

    Investigational medicinal product name
    Axicabtagene Ciloleucel
    Investigational medicinal product code
    Other name
    Yescarta®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg.

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Arm title
    Phase 2 (Safety Management Study): Cohort 3
    Arm description
    Participants with relapsed or refractory transplant ineligible DLBCL, PMBCL, or TFL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants also received a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0) and tocilizumab (8 mg/kg IV over 1 hour (not to exceed 800 mg)) on Day 2).
    Arm type
    Experimental

    Investigational medicinal product name
    Axicabtagene Ciloleucel
    Investigational medicinal product code
    Other name
    Yescarta®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg.

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Levetiracetam
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Arm title
    Phase 2 (Safety Management Study): Cohort 4
    Arm description
    Participants with r/r DLBCL,PMBCL,TFL,or high-grade B-cell lymphoma(HGBCL)after 2 systemic lines of therapy will receive optional bridging therapy(dexamethasone 20mg to 40mg,eitherorally or IV daily for 1 to 4 days or 1g/m^2 of high-dose methylprednisolone(HDMP)for 3 days with rituximab at 375mg/m^2 weekly for 3 weeks or bendamustine 90 mg/m^2 on Days 1 and 2 and rituximab 375mg/m^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3;followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW. Participants will receive a prophylactic regimen of levetiracetam(750 mg orally or IV twice daily(BID)starting on Day 0).Participants received tocilizumab(initiated on persistent Grade 1 cytokine release syndrome(CRS)for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).
    Arm type
    Experimental

    Investigational medicinal product name
    Levetiracetam
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Axicabtagene Ciloleucel
    Investigational medicinal product code
    Other name
    Yescarta®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg.

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    High-dose methylprednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Arm title
    Phase 2 (Safety Management Study): Cohort 5
    Arm description
    Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy received debulking therapy (R-CHOP:rituximab 375mg/m^2 D1,doxorubicin 50mg/m^2 D1,prednisone 100mg D1 to D5,cyclophosphamide 750mg/m^2 D1,vincristine 1.4 mg/m^2 D1 or R-ICE:rituximab 375mg/ m^2 D1,ifosfamide 5g/m^2 24h-CI D2,carboplatin AUC5 D2 maximum dose 800mg,etoposide 100 mg/m^2/day D1 to D3 or R-GEMOX:rituximab 375mg/m^2 D1,gemcitabine 1000mg/m^2 D2,oxaliplatin 100mg/m^2 D2 or R-GDP:rituximab 375mg/m^2 D1 or D8,gemcitabine 1g/m^2 D1 & D8,dexamethasone 40mg D1 to D4,cisplatin 75mg/m^2 D1(or carboplatin AUC5 D1) or radiotherapy:20 to 30 Gy), conditioning chemotherapy (fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants also received a prophylactic regimen of levetiracetam (750 mg orally or IV BID starting on D0).D=Day.
    Arm type
    Experimental

    Investigational medicinal product name
    Axicabtagene Ciloleucel
    Investigational medicinal product code
    Other name
    Yescarta®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg.

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Levetiracetam
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Ifosfamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Etoposide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Oxaliplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Arm title
    Phase 2 (Safety Management Study): Cohort 6
    Arm description
    Participants with r/r DLBCL,PMBCL,TFL orHGBCL after 2 systemic lines of therapy may receive bridging therapy(dexamethasone 20mg to 40mg,orally or IV daily for 1 to 4 days or 1g/m^2 HDMP for 3 days with rituximab at 375mg/m^2 weekly for 3 weeks or bendamustine 90 mg/m^2 on Days 1 and 2 and rituximab 375mg/m^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.Participants will also receive a prophylactic regimen of levetiracetam 750 mg orally or IV twice daily(BID)starting on Day 0)and corticosteroids(dexamethasone, 10 mg once daily on Days 0, 1, and 2).Participants received tocilizumab(initiated on persistent Grade 1 CRS for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).
    Arm type
    Experimental

    Investigational medicinal product name
    Levetiracetam
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Axicabtagene Ciloleucel
    Investigational medicinal product code
    Other name
    Yescarta®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg.

    Investigational medicinal product name
    Fludarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Methylprednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    High-dose methylprednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered according to package insert

    Number of subjects in period 1
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Started
    8
    81
    30
    42
    46
    58
    42
    Completed
    0
    0
    0
    0
    0
    0
    0
    Not completed
    8
    81
    30
    42
    46
    58
    42
         Enrolled but did not take axicabtagene ciloleucel
    1
    4
    6
    4
    5
    8
    2
         Death
    5
    53
    11
    20
    16
    32
    17
         Full consent withdrawal
    -
    -
    -
    1
    3
    -
    3
         Reason not specified
    2
    19
    11
    17
    21
    17
    19
         Lost to follow-up
    -
    5
    2
    -
    1
    1
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot
    Reporting group description
    Participants with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) received conditioning chemotherapy (fludarabine 30 mg/m^2 intravenously [IV] over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of body weight (BW) on Day 0.

    Reporting group title
    Phase 2 (Pivotal Study): Cohort 1
    Reporting group description
    Participants with refractory DLBCL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.

    Reporting group title
    Phase 2 (Pivotal Study): Cohort 2
    Reporting group description
    Participants with refractory PMBCL or TFL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 3
    Reporting group description
    Participants with relapsed or refractory transplant ineligible DLBCL, PMBCL, or TFL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants also received a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0) and tocilizumab (8 mg/kg IV over 1 hour (not to exceed 800 mg)) on Day 2).

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 4
    Reporting group description
    Participants with r/r DLBCL,PMBCL,TFL,or high-grade B-cell lymphoma(HGBCL)after 2 systemic lines of therapy will receive optional bridging therapy(dexamethasone 20mg to 40mg,eitherorally or IV daily for 1 to 4 days or 1g/m^2 of high-dose methylprednisolone(HDMP)for 3 days with rituximab at 375mg/m^2 weekly for 3 weeks or bendamustine 90 mg/m^2 on Days 1 and 2 and rituximab 375mg/m^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3;followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW. Participants will receive a prophylactic regimen of levetiracetam(750 mg orally or IV twice daily(BID)starting on Day 0).Participants received tocilizumab(initiated on persistent Grade 1 cytokine release syndrome(CRS)for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 5
    Reporting group description
    Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy received debulking therapy (R-CHOP:rituximab 375mg/m^2 D1,doxorubicin 50mg/m^2 D1,prednisone 100mg D1 to D5,cyclophosphamide 750mg/m^2 D1,vincristine 1.4 mg/m^2 D1 or R-ICE:rituximab 375mg/ m^2 D1,ifosfamide 5g/m^2 24h-CI D2,carboplatin AUC5 D2 maximum dose 800mg,etoposide 100 mg/m^2/day D1 to D3 or R-GEMOX:rituximab 375mg/m^2 D1,gemcitabine 1000mg/m^2 D2,oxaliplatin 100mg/m^2 D2 or R-GDP:rituximab 375mg/m^2 D1 or D8,gemcitabine 1g/m^2 D1 & D8,dexamethasone 40mg D1 to D4,cisplatin 75mg/m^2 D1(or carboplatin AUC5 D1) or radiotherapy:20 to 30 Gy), conditioning chemotherapy (fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants also received a prophylactic regimen of levetiracetam (750 mg orally or IV BID starting on D0).D=Day.

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 6
    Reporting group description
    Participants with r/r DLBCL,PMBCL,TFL orHGBCL after 2 systemic lines of therapy may receive bridging therapy(dexamethasone 20mg to 40mg,orally or IV daily for 1 to 4 days or 1g/m^2 HDMP for 3 days with rituximab at 375mg/m^2 weekly for 3 weeks or bendamustine 90 mg/m^2 on Days 1 and 2 and rituximab 375mg/m^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.Participants will also receive a prophylactic regimen of levetiracetam 750 mg orally or IV twice daily(BID)starting on Day 0)and corticosteroids(dexamethasone, 10 mg once daily on Days 0, 1, and 2).Participants received tocilizumab(initiated on persistent Grade 1 CRS for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).

    Reporting group values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6 Total
    Number of subjects
    8 81 30 42 46 58 42 307
    Age categorical
    Units: Subjects
        18 – 64 Years
    5 64 21 33 32 39 21 215
        65 – 84 Years
    3 17 9 9 14 19 20 91
        85 Years and Over
    0 0 0 0 0 0 1 1
    Gender categorical
    Units: Subjects
        Female
    2 27 7 18 13 15 18 100
        Male
    6 54 23 24 33 43 24 207
    Race
    Units: Subjects
        White
    6 71 23 34 37 39 36 246
        Other or More Than One Race
    1 6 3 3 9 12 5 39
        Black or African American
    1 3 1 4 0 2 1 12
        Asian
    0 1 3 1 0 5 0 10
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    1 18 2 6 0 1 3 31
        Not Hispanic or Latino
    7 63 28 36 45 57 39 275
        Unknown or Not Reported
    0 0 0 0 1 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot
    Reporting group description
    Participants with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) received conditioning chemotherapy (fludarabine 30 mg/m^2 intravenously [IV] over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of body weight (BW) on Day 0.

    Reporting group title
    Phase 2 (Pivotal Study): Cohort 1
    Reporting group description
    Participants with refractory DLBCL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.

    Reporting group title
    Phase 2 (Pivotal Study): Cohort 2
    Reporting group description
    Participants with refractory PMBCL or TFL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 3
    Reporting group description
    Participants with relapsed or refractory transplant ineligible DLBCL, PMBCL, or TFL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants also received a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0) and tocilizumab (8 mg/kg IV over 1 hour (not to exceed 800 mg)) on Day 2).

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 4
    Reporting group description
    Participants with r/r DLBCL,PMBCL,TFL,or high-grade B-cell lymphoma(HGBCL)after 2 systemic lines of therapy will receive optional bridging therapy(dexamethasone 20mg to 40mg,eitherorally or IV daily for 1 to 4 days or 1g/m^2 of high-dose methylprednisolone(HDMP)for 3 days with rituximab at 375mg/m^2 weekly for 3 weeks or bendamustine 90 mg/m^2 on Days 1 and 2 and rituximab 375mg/m^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3;followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW. Participants will receive a prophylactic regimen of levetiracetam(750 mg orally or IV twice daily(BID)starting on Day 0).Participants received tocilizumab(initiated on persistent Grade 1 cytokine release syndrome(CRS)for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 5
    Reporting group description
    Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy received debulking therapy (R-CHOP:rituximab 375mg/m^2 D1,doxorubicin 50mg/m^2 D1,prednisone 100mg D1 to D5,cyclophosphamide 750mg/m^2 D1,vincristine 1.4 mg/m^2 D1 or R-ICE:rituximab 375mg/ m^2 D1,ifosfamide 5g/m^2 24h-CI D2,carboplatin AUC5 D2 maximum dose 800mg,etoposide 100 mg/m^2/day D1 to D3 or R-GEMOX:rituximab 375mg/m^2 D1,gemcitabine 1000mg/m^2 D2,oxaliplatin 100mg/m^2 D2 or R-GDP:rituximab 375mg/m^2 D1 or D8,gemcitabine 1g/m^2 D1 & D8,dexamethasone 40mg D1 to D4,cisplatin 75mg/m^2 D1(or carboplatin AUC5 D1) or radiotherapy:20 to 30 Gy), conditioning chemotherapy (fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants also received a prophylactic regimen of levetiracetam (750 mg orally or IV BID starting on D0).D=Day.

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 6
    Reporting group description
    Participants with r/r DLBCL,PMBCL,TFL orHGBCL after 2 systemic lines of therapy may receive bridging therapy(dexamethasone 20mg to 40mg,orally or IV daily for 1 to 4 days or 1g/m^2 HDMP for 3 days with rituximab at 375mg/m^2 weekly for 3 weeks or bendamustine 90 mg/m^2 on Days 1 and 2 and rituximab 375mg/m^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.Participants will also receive a prophylactic regimen of levetiracetam 750 mg orally or IV twice daily(BID)starting on Day 0)and corticosteroids(dexamethasone, 10 mg once daily on Days 0, 1, and 2).Participants received tocilizumab(initiated on persistent Grade 1 CRS for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).

    Primary: Phase 2 Pivotal Study (Cohorts 1 and 2): Overall Response Rate (ORR) as Assessed by Investigator per Revised International Working Group (IWG) Response Criteria for Malignant Lymphoma

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    End point title
    Phase 2 Pivotal Study (Cohorts 1 and 2): Overall Response Rate (ORR) as Assessed by Investigator per Revised International Working Group (IWG) Response Criteria for Malignant Lymphoma [1] [2]
    End point description
    ORR was defined either a complete response (CR) or partial response (PR),assessed by the study investigators by revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007).CR: complete disappearance of all detectable clinical evidence of disease and symptoms; all lymph nodes and nodal masses must have regressed to normal size; spleen and/or liver must be normal size,not be palpable,and no nodules;bone marrow aspirate and biopsy must show no evidence of disease.PR: a ≥ 50% decrease in sum of product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses;no increase in size of nodes, liver or spleen and no new sites; multiple splenic and hepatic nodules regress by ≥ 50% in the SPD; > 50% decrease in the greatest transverse diameter for single nodules. 95% confidence interval (CI) was calculated by Clopper-Pearson method. The Modified Intent-to-Treat (mITT) analysis set included all participants treated with at least 1.0 x 10^6 anti-CD19 CAR T cells/kg.
    End point type
    Primary
    End point timeframe
    First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 7.7 years)
    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: No statistical comparison was planned or performed.
    [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: As the endpoint was focused on only the arms under Phase 2 (Cohorts 1 and 2) of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2
    Number of subjects analysed
    77
    24
    Units: percentage of participants
        number (confidence interval 95%)
    83 (73 to 91)
    83 (63 to 95)
    No statistical analyses for this end point

    Primary: Phase 1 Study: Number of Participants Experiencing Adverse Events (AEs) defined as Dose Limiting Toxicities (DLTs)

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    End point title
    Phase 1 Study: Number of Participants Experiencing Adverse Events (AEs) defined as Dose Limiting Toxicities (DLTs) [3] [4]
    End point description
    DLT was defined as axicabtagene ciloleucel-related events with onset within first 30 days following infusion:Grade (GR) 4 neutropenia lasting > 21 days and GR 4 thrombocytopenia lasting > 35 days from day of cell transfer;Any axicabtagene ciloleucel-related AE requiring intubation; All other GR 3 toxicities lasting > 3 days and all GR 4 toxicities, exception conditions: aphasia/dysphasia or confusion/cognitive disturbance which resolved to GR ≤ 1 ; fever GR 3; myelosuppression, decreased hemoglobin, neutropenia and thrombocytopenia ; immediate hypersensitivity reactions occurring within 2 hours of cell infusion that were reversible to a ≤ GR 2 within 24 hours of cell administration; hypogammaglobulinemia GR 3 or 4. DLT-Evaluable Analysis Set included participants treated in Phase 1 dosing cohort who received the target dose and were followed for at least 30 days after the axicabtagene ciloleucel infusion.
    End point type
    Primary
    End point timeframe
    First infusion date of axicabtagene ciloleucel up to 30 days
    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: No statistical comparison was planned or performed.
    [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: As the endpoint was focused on only the arms under Phase 1 of the study, all the arms in the baseline period were not included.
    End point values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot
    Number of subjects analysed
    6
    Units: participants
    1
    No statistical analyses for this end point

    Primary: Phase 2 Safety Management Study (Cohort 3): Percentage of Participants With Treatment-Emergent Cytokine Release Syndrome (CRS) and Neurologic Toxicities by Severity Grades

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    End point title
    Phase 2 Safety Management Study (Cohort 3): Percentage of Participants With Treatment-Emergent Cytokine Release Syndrome (CRS) and Neurologic Toxicities by Severity Grades [5] [6]
    End point description
    TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1:No life threatening symptoms and require symptomatic treatment only;Grade2:Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms, requirements for ventilator support or continuous venovenous hemodialysis (CVVHD),and Grade 5: Death. Neurologic toxicities were graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.Grade 1:Mild, asymptomatic or mild symptoms; Grade 2:Moderate and minimal, local or noninvasive intervention;Grade 3: Severe or medically significant but not life-threatening,hospitalization;Grade 4: Life-threatening and urgent intervention indicated;Grade 5: Death related to AE. The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel.
    End point type
    Primary
    End point timeframe
    First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 6.8 years)
    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: No statistical comparison was planned or performed.
    [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: As the endpoint was focused on only the arms under Phase 2 (Cohort 3) of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Safety Management Study): Cohort 3
    Number of subjects analysed
    38
    Units: percentage of participants
    number (not applicable)
        Worst Grade 1 CRS
    34
        Worst Grade 2 CRS
    55
        Worst Grade 3 CRS
    0
        Worst Grade 4 CRS
    3
        Worst Grade 5 CRS
    0
        Worst Grade ≥ 3 CRS
    3
        Worst Grade 1 Neurologic Toxicities
    24
        Worst Grade 2 Neurologic Toxicities
    21
        Worst Grade 3 Neurologic Toxicities
    37
        Worst Grade 4 Neurologic Toxicities
    3
        Worst Grade 5 Neurologic Toxicities
    3
        Worst Grade ≥ 3 Neurologic Toxicities
    42
    No statistical analyses for this end point

    Primary: Phase 2 Safety Management Study (Cohort 4): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades

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    End point title
    Phase 2 Safety Management Study (Cohort 4): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades [7] [8]
    End point description
    TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE. The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel.
    End point type
    Primary
    End point timeframe
    First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 5.4 years)
    Notes
    [7] - 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: No statistical comparison was planned or performed.
    [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: No statistical comparison was planned or performed.
    End point values
    Phase 2 (Safety Management Study): Cohort 4
    Number of subjects analysed
    41
    Units: percentage of participants
    number (not applicable)
        Worst Grade 1 CRS
    32
        Worst Grade 2 CRS
    59
        Worst Grade 3 CRS
    2
        Worst Grade 4 CRS
    0
        Worst Grade 5 CRS
    0
        Worst Grade ≥ 3 CRS
    2
        Worst Grade 1 Neurologic Toxicities
    34
        Worst Grade 2 Neurologic Toxicities
    10
        Worst Grade 3 Neurologic Toxicities
    17
        Worst Grade 4 Neurologic Toxicities
    0
        Worst Grade 5 Neurologic Toxicities
    0
        Worst Grade ≥ 3 Neurologic Toxicities
    17
    No statistical analyses for this end point

    Primary: Phase 2 Safety Management Study (Cohort 5): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades

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    End point title
    Phase 2 Safety Management Study (Cohort 5): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades [9] [10]
    End point description
    TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE. The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel.
    End point type
    Primary
    End point timeframe
    First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 4.4 years)
    Notes
    [9] - 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: No statistical comparison was planned or performed.
    [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: The data has been reported only for the specified arms for which participants were available and data was evaluable for the specified outcome measure.
    End point values
    Phase 2 (Safety Management Study): Cohort 5
    Number of subjects analysed
    50
    Units: percentage of participants
    number (not applicable)
        Worst Grade 1 CRS
    38
        Worst Grade 2 CRS
    46
        Worst Grade 3 CRS
    0
        Worst Grade 4 CRS
    2
        Worst Grade 5 CRS
    0
        Worst Grade ≥ 3 CRS
    2
        Worst Grade 1 Neurologic Toxicities
    26
        Worst Grade 2 Neurologic Toxicities
    18
        Worst Grade 3 Neurologic Toxicities
    10
        Worst Grade 4 Neurologic Toxicities
    2
        Worst Grade 5 Neurologic Toxicities
    0
        Worst Grade ≥ 3 Neurologic Toxicities
    12
    No statistical analyses for this end point

    Primary: Phase 2 Safety Management Study (Cohort 6): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades

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    End point title
    Phase 2 Safety Management Study (Cohort 6): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades [11] [12]
    End point description
    TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE. The Safety Analysis Set included all participants treated with any dose of axicabtagene ciloleucel.
    End point type
    Primary
    End point timeframe
    First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 4.1 years)
    Notes
    [11] - 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: No statistical comparison was planned or performed.
    [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: The data has been reported only for the specified arms for which participants were available and data was evaluable for the specified outcome measure.
    End point values
    Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    40
    Units: percentage of participants
    number (not applicable)
        Worst Grade 1 CRS
    35
        Worst Grade 2 CRS
    45
        Worst Grade 3 CRS
    0
        Worst Grade 4 CRS
    0
        Worst Grade 5 CRS
    0
        Worst Grade ≥ 3 CRS
    0
        Worst Grade 1 Neurologic Toxicities
    23
        Worst Grade 2 Neurologic Toxicities
    18
        Worst Grade 3 Neurologic Toxicities
    8
        Worst Grade 4 Neurologic Toxicities
    5
        Worst Grade 5 Neurologic Toxicities
    5
        Worst Grade ≥ 3 Neurologic Toxicities
    18
    No statistical analyses for this end point

    Secondary: Phase 2: Duration of Response (DOR) as Assessed by Investigator per Revised IWG Response Criteria for Malignant Lymphoma

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    End point title
    Phase 2: Duration of Response (DOR) as Assessed by Investigator per Revised IWG Response Criteria for Malignant Lymphoma [13]
    End point description
    Among participants who experience an objective response (OR), DOR was defined as the date of their first objective response (CR or PR which was subsequently confirmed) to disease progression per the revised IWG Response Criteria for Malignant Lymphoma or death regardless of cause. CR and PR as defined in outcome measure 1. Participants in the mITT Analysis Set with objective response were analyzed. 99.99=median was not estimable because almost 50% of participants were censored;99= lower limit of 95% CI was not estimable because almost 50% of participants were censored; 99999= upper limit of 95% CI was not estimable because almost 50% of participants were censored.
    End point type
    Secondary
    End point timeframe
    First OR to last follow-up visit (maximum duration: 7.7, 6.8, 5.4, 4.4, 4.1 years for Cohorts 1, 2, 3, 4, 5, and 6 respectively)
    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: As the endpoint was focused on only the arms under Phase 2 of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    64
    20
    24
    31
    36
    38
    Units: months
        median (confidence interval 95%)
    5.0 (2.1 to 34.7)
    75.4 (11.1 to 9999)
    99.99 (5.0 to 99999)
    99.99 (99 to 99999)
    27.5 (2.2 to 99999)
    99.99 (7.8 to 99999)
    No statistical analyses for this end point

    Secondary: Phase 1 Study: ORR as Assessed by Investigator per Revised IWG Response Criteria for Malignant Lymphoma

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    End point title
    Phase 1 Study: ORR as Assessed by Investigator per Revised IWG Response Criteria for Malignant Lymphoma [14]
    End point description
    ORR was defined as the percentage of participants achieving either a CR or a PR, as assessed by the study investigators using revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; all lymph nodes and nodal masses must have regressed to normal size; spleen and/or liver must be normal size, not be palpable, and no nodules; bone marrow aspirate and biopsy must show no evidence of disease. PR: a ≥ 50% decrease in SPD of up to 6 of the largest dominant nodes or nodal masses; no increase in size of nodes, liver or spleen and no new sites of disease; multiple splenic and hepatic nodules (if present) must regress by ≥ 50% in the SPD; > 50% decrease in the greatest transverse diameter for single nodules. Participants in the Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of axicabtagene ciloleucel to the data cutoff date of 27 January 2017 (maximum: 20 months)
    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: As the endpoint was focused on only the arms under Phase 1 of the study, all the arms in the baseline period were not included.
    End point values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot
    Number of subjects analysed
    7
    Units: percentage of participants
        number (not applicable)
    71
    No statistical analyses for this end point

    Secondary: Phase 2 Pivotal Study (Cohorts 1 and 2): ORR per Independent Radiological Review Committee (IRRC)

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    End point title
    Phase 2 Pivotal Study (Cohorts 1 and 2): ORR per Independent Radiological Review Committee (IRRC) [15]
    End point description
    ORR was defined as the percentage of participants achieving either a CR or a PR, as assessed by the IRRC using revised IWG Response Criteria for Malignant Lymphoma. CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; all lymph nodes and nodal masses must have regressed to normal size; spleen and/or liver must be normal size, not be palpable, and no nodules; bone marrow aspirate and biopsy must show no evidence of disease. PR: a ≥ 50% decrease in SPD of up to 6 of the largest dominant nodes or nodal masses; no increase in size of nodes, liver or spleen and no new sites of disease; multiple splenic and hepatic nodules (if present) must regress by ≥ 50% in the SPD; > 50% decrease in the greatest transverse diameter for single nodules. 95% CI was calculated by Clopper-Pearson method. Participants in the mITT Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of axicabtagene ciloleucel to the data cutoff date of 11 August 2018 (maximum: 2.7 years)
    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: As the endpoint was focused on the arms under Phase 2 (Cohorts 1 and 2) of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2
    Number of subjects analysed
    77
    24
    Units: percentage of participants
        number (confidence interval 95%)
    70 (59 to 80)
    88 (68 to 97)
    No statistical analyses for this end point

    Secondary: Phase 2 Safety Management Study (Cohorts 3, 4, 5, and 6): ORR as Assessed by Investigator per the Revised IWG Response Criteria for Malignant Lymphoma

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    End point title
    Phase 2 Safety Management Study (Cohorts 3, 4, 5, and 6): ORR as Assessed by Investigator per the Revised IWG Response Criteria for Malignant Lymphoma [16]
    End point description
    ORR was defined as the percentage of participants achieving either a CR or a PR, as assessed by the study investigators using revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; all lymph nodes and nodal masses must have regressed to normal size; spleen and/or liver must be normal size, not be palpable, and no nodules; bone marrow aspirate and biopsy must show no evidence of disease. PR: a ≥ 50% decrease in SPD of up to 6 of the largest dominant nodes or nodal masses; no increase in size of nodes, liver or spleen and no new sites of disease; multiple splenic and hepatic nodules (if present) must regress by ≥ 50% in the SPD; > 50% decrease in the greatest transverse diameter for single nodules. 95% CI was calculated by Clopper-Pearson method. Participants in the mITT Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of axicabtagene ciloleucel to last follow-up visit (maximum duration: 6.8, 5.4, 4.4, 4.1 years for Cohorts 3, 4, 5, and 6 respectively)
    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: As the endpoint was focused on only the arms under the Phase 2 safety Management Study (Cohorts 3, 4, 5, and 6) of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    38
    41
    50
    40
    Units: percentage of participants
        number (confidence interval 95%)
    63 (46 to 78)
    76 (60 to 88)
    72 (58 to 84)
    95 (83 to 99)
    No statistical analyses for this end point

    Secondary: Phase 2: Progression-Free Survival (PFS) as Assessed by Investigator per Revised IWG Response Criteria for Malignant Lymphoma

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    End point title
    Phase 2: Progression-Free Survival (PFS) as Assessed by Investigator per Revised IWG Response Criteria for Malignant Lymphoma [17]
    End point description
    PFS was defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per the revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007) or death from any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored. Disease progression was defined by at least one of ≥ 50% increase from nadir in the sum of the products of at least 2 lymph nodes, a 50% increase in the product of the diameters of a single lymph node; appearance of a new lesion > 1.5 cm in any axis; ≥ 50% increase in size of splenic or hepatic nodules; ≥ 50% increase in the longest diameter node > 1 cm in its short axis. KM estimates was used for analyses. Participants in the mITT Analysis Set were analyzed. 99.99=median was not estimable because almost 50% of participants were censored;99999= upper limit of 95% 99.99=median was not estimable because almost 50% of participants were censored.
    End point type
    Secondary
    End point timeframe
    First infusion date of axicabtagene ciloleucel to disease progression or death regardless of cause (maximum duration: 7.7, 6.8, 5.4, 4.4, 4.1 years for Cohorts 1, 2, 3, 4, 5, and 6 respectively)
    Notes
    [17] - 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: As the endpoint was focused on only the arms under Phase 2 of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    77
    24
    38
    41
    50
    40
    Units: months
        median (confidence interval 95%)
    5.1 (3.0 to 8.8)
    49.1 (3.7 to 99999)
    6.2 (2.4 to 99999)
    99.99 (3.0 to 99999)
    3.1 (2.9 to 29.1)
    99.99 (8.7 to 99999)
    No statistical analyses for this end point

    Secondary: Phase 2 Pivotal Study (Cohorts 1 and 2): Duration of Response (DOR) Using IRRC per Cheson 2007

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    End point title
    Phase 2 Pivotal Study (Cohorts 1 and 2): Duration of Response (DOR) Using IRRC per Cheson 2007 [18]
    End point description
    Among participants who experience an objective response, DOR was defined as the date of their first objective response (CR or PR which was subsequently confirmed) to PD, as assessed by the IRRC using revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007) or death regardless of cause. CR and PR as defined in outcome measure 1. PD was defined by at least one:≥ 50% increase from nadir in the sum of the products of at least 2 lymph nodes,or at least a 50% increase in the product of the diameters of a single node;appearance of a new lesion > 1.5 cm in any axis; ≥ 50% increase in size of snodules;≥ 50% increase in the longest diameter of anode > 1 cm in its short axis. Kaplan-Meier (KM) estimates. Participants in the mITT Analysis Set with objective response were analyzed. 99.99=median was not estimable because almost 50% of participants were censored;99999= upper limit of CI was not estimable because almost 50% of participants were censored.
    End point type
    Secondary
    End point timeframe
    First objective response up to the data cutoff date of 11 August 2018 (maximum: 2.7 years)
    Notes
    [18] - 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: As the endpoint was focused on the arms under Phase 2 (Cohorts 1 and 2) of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2
    Number of subjects analysed
    54
    21
    Units: months
        median (confidence interval 95%)
    99.99 (5.4 to 99999)
    99.99 (11.1 to 99999)
    No statistical analyses for this end point

    Secondary: Phase 2: Overall Survival (OS)

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    End point title
    Phase 2: Overall Survival (OS) [19]
    End point description
    OS was defined as the time from axicabtagene ciloleucel infusion to the date of death. Participants who did not die by the analysis data cutoff date were censored at their last contact date. KM estimates was used for analyses. Participants in the mITT Analysis Set were analyzed. 99.99=median was not estimable because almost 50% of participants were censored;99999= upper limit of 95% 99.99=median was not estimable because almost 50% of participants were censored.
    End point type
    Secondary
    End point timeframe
    First infusion date of axicabtagene ciloleucel to the date of death regardless of cause (maximum duration: 7.7, 6.8, 5.4, 4.4, 4.1 years for Cohorts 1, 2, 3, 4, 5, and 6 respectively)
    Notes
    [19] - 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: As the endpoint was focused on only the arms under Phase 2 of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    77
    24
    38
    41
    50
    40
    Units: months
        median (confidence interval 95%)
    15.4 (10.4 to 45.7)
    99.99 (15.0 to 99999)
    34.8 (5.4 to 99999)
    99.99 (14.6 to 99999)
    20.6 (12.6 to 43.1)
    99.99 (18.9 to 99999)
    No statistical analyses for this end point

    Secondary: Phase 2 Pivotal Study (Cohorts 1 and 2): Best Overall Response Using IRRC per Cheson 2007

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    End point title
    Phase 2 Pivotal Study (Cohorts 1 and 2): Best Overall Response Using IRRC per Cheson 2007 [20]
    End point description
    The best overall response for each participant was based on the assessments of response (CR, PR, stable disease [SD], PD, and not done [ND]) made by the the IRRC using IWG 2007 criteria (Cheson et al, 2007). CR and PR as defined in outcome measure 1. PD defined by at least one of the following: ≥ 50% increase from nadir in the sum of the products of at least 2 lymph nodes, or at least a 50% increase in the product of the diameters of a single lymph node; appearance of a new lesion > 1.5 cm in any axis; ≥ 50% increase in size of splenic or hepatic nodules; ≥ 50% increase in the longest diameter of any single previously identified node > 1 cm in its short axis. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentage of participants with best overall response of CR, PR, SD, PD, and ND was reported. Participants in the mITT Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of axicabtagene ciloleucel to the data cutoff date of 11 August 2018 (maximum: 2.7 years)
    Notes
    [20] - 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: As the endpoint was focused on the arms under Phase 2 (Cohorts 1 and 2) of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2
    Number of subjects analysed
    77
    24
    Units: percentage of participants
    number (not applicable)
        CR
    51
    67
        PR
    19
    21
        SD
    21
    4
        PD
    8
    4
        ND
    1
    4
    No statistical analyses for this end point

    Secondary: Phase 2 Pivotal Study (Cohorts 1 and 2): PFS Using IRRC per Cheson 2007

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    End point title
    Phase 2 Pivotal Study (Cohorts 1 and 2): PFS Using IRRC per Cheson 2007 [21]
    End point description
    PFS was defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression as assessed by the IRRC using revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007) or death from any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date. PD defined by at least: ≥ 50% increase from nadir in the sum of the products of at least 2 lymph nodes,or at least a 50% increase in the product of the diameters of a single node; appearance of a new lesion > 1.5 cm; ≥ 50% increase in size of nodules; ≥ 50% increase in the longest diameter of any node > 1 cm in its short axis. KM estimates were used for analyses. Participants in the mITT Analysis Set were analyzed. 99.99=median was not estimable because almost 50% of participants were censored;99999= upper limit of 95% of CI was not estimable because almost 50% of participants were censored.
    End point type
    Secondary
    End point timeframe
    First infusion date of axicabtagene ciloleucel to the data cutoff date of 11 August 2018 (maximum: 2.7 years)
    Notes
    [21] - 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: As the endpoint was focused on only the arms under Phase 2 (Cohorts 1 and 2) of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2
    Number of subjects analysed
    77
    24
    Units: months
        median (confidence interval 95%)
    6.9 (4.5 to 15.0)
    99.99 (9.0 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
    End point description
    An adverse event was defined as any untoward medical occurrence in a clinical trial participants. The event did not necessarily have a relationship with study treatment. Adverse events included worsening of a pre-existing medical condition. Worsening indicated that the pre-existing medical condition had increased in severity, frequency, and/or duration or had an association with a worse outcome. A pre-existing condition that had not worsened during the study or involved an intervention such as elective cosmetic surgery or a medical procedure while on study, was not considered an adverse event. TEAE was defined as any AE with onset on or after the start of treatment. Participants in the Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of axicabtagene ciloleucel up to last follow up visit (maximum duration: 7.7 years)
    End point values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    7
    77
    24
    38
    41
    50
    40
    Units: percentage of participants
        number (not applicable)
    100
    100
    100
    100
    100
    100
    100
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Clinically Significant Changes in Laboratory Values Reported as Grade 3 or Higher TEAEs

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    End point title
    Percentage of Participants With Clinically Significant Changes in Laboratory Values Reported as Grade 3 or Higher TEAEs
    End point description
    Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening. Participants in the Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of axicabtagene ciloleucel up to last follow up visit (maximum duration: 7.7 years)
    End point values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    7
    77
    24
    38
    41
    50
    40
    Units: percentage of participants
        number (not applicable)
    100
    96
    96
    97
    98
    100
    100
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Anti-Axicabtagene Ciloleucel Antibodies

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    End point title
    Percentage of Participants with Anti-Axicabtagene Ciloleucel Antibodies
    End point description
    Participants in the Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    First infusion date of axicabtagene ciloleucel up to last follow-up visit (maximum duration: 7.7, 6.8, 5.4, 4.4, 4.1 years for Phase 1 and Phase 2 Cohorts 1, 2, 3, 4, 5, and 6 respectively)
    End point values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    7
    77
    24
    38
    41
    50
    40
    Units: percentage of participants
        number (not applicable)
    29
    5
    8
    11
    0
    8
    8
    No statistical analyses for this end point

    Secondary: Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood

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    End point title
    Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood
    End point description
    Peak was defined as the maximum number of CAR T cells measured post-infusion. Participants in the Safety Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 60 (for Phase 1 and Phase 2 Cohorts 1, 2, and 3); Baseline up to Month 24 (for Phase 2 Cohorts 4, 5, and 6)
    End point values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    6
    76
    22
    36
    39
    49
    40
    Units: cells/µL
        median (inter-quartile range (Q1-Q3))
    58.512 (18.028 to 147.732)
    31.512 (12.445 to 74.746)
    58.633 (27.884 to 103.190)
    53.670 (22.813 to 146.075)
    52.91 (27.25 to 92.78)
    26.63 (12.52 to 117.53)
    64.38 (6.27 to 131.24)
    No statistical analyses for this end point

    Secondary: Pharmacodynamics: Peak Level of Cytokines in Serum (Phase 1 and Phase 2 Cohorts 1, 2, and 3)

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    End point title
    Pharmacodynamics: Peak Level of Cytokines in Serum (Phase 1 and Phase 2 Cohorts 1, 2, and 3) [22]
    End point description
    Peak was defined as the maximum post-baseline level of the cytokine. Following key cytokines were measured: interferon-gamma induced protein 10 (IP-10), ferritin, granzyme B, intercellular adhesion molecule (ICAM-1), interferon-gamma (IFN-gamma), interleukin-1 receptor antagonist (IL-1RA), IL-2, interleukin-2 receptor alpha (IL-2 R alpha), IL-6, IL-7, IL-8, IL-10, IL-15, perforin, tumor necrosis factor alpha (TNF alpha), and vascular cell adhesion molecule- 1 (VCAM-1). Participants in the Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 3
    Notes
    [22] - 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: The data has been reported only for the specified arms for which participants were available and data was evaluable for the specified outcome measure.
    End point values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3
    Number of subjects analysed
    7
    77
    24
    38
    Units: pg/mL
    median (full range (min-max))
        IP-10
    2000.0 (147.0 to 2000.0)
    2000.0 (628.1 to 2000.0)
    2000.0 (434.2 to 2000.0)
    2000.0 (541.0 to 2000.0)
        Granzyme B
    33.1 (0.6 to 463.8)
    31.1 (1.0 to 3306.0)
    17.3 (1.0 to 406.8)
    44.1 (1.0 to 534.6)
        ICAM-1
    792754.3 (537796.8 to 2424877.7)
    1322829.3 (557025.0 to 7495123.2)
    989188.4 (544589.3 to 4588974.8)
    1009966.4 (256768.6 to 4879749.7)
        IFN-gamma
    792.0 (81.1 to 1876.0)
    493.8 (32.4 to 1876.0)
    364.9 (7.5 to 1876.0)
    1857.2 (65.0 to 1876.0)
        IL-1 RA
    2173.3 (544.3 to 4000.0)
    2371.2 (510.8 to 4000.0)
    1999.9 (649.9 to 4000.0)
    2160.5 (653.7 to 4000.0)
        IL-2
    18.4 (3.1 to 91.0)
    25.0 (0.9 to 123.1)
    13.4 (0.9 to 63.7)
    20.0 (0.9 to 189.4)
        IL-2 R alpha
    16872.7 (2189.0 to 34044.5)
    14383.7 (78.0 to 100000.0)
    7817.3 (78.0 to 66024.6)
    12386.4 (3002.6 to 100000.0)
        IL-6
    305.3 (2.4 to 976.0)
    89.4 (3.5 to 976.0)
    44.6 (3.6 to 976.0)
    921.8 (13.3 to 976.0)
        IL-7
    51.5 (31.2 to 71.5)
    38.9 (13.8 to 153.5)
    44.1 (27.9 to 98.8)
    38.8 (19.1 to 83.8)
        IL-8
    86.4 (17.1 to 750.0)
    118.4 (14.2 to 750.0)
    77.2 (9.8 to 750.0)
    120.9 (10.3 to 750.0)
        IL-10
    52.5 (3.8 to 614.0)
    43.9 (0.7 to 466.0)
    18.8 (0.7 to 263.6)
    48.2 (1.8 to 466.0)
        IL-15
    57.1 (18.7 to 271.3)
    56.5 (13.1 to 226.6)
    47.6 (11.3 to 195.2)
    50.3 (21.9 to 537.3)
        Perforin
    5389.0 (2582.7 to 20724.3)
    11309.5 (2282.3 to 39818.9)
    8278.7 (2332.6 to 31857.7)
    15411.9 (4327.4 to 30575.9)
        TNF alpha
    10.5 (1.8 to 443.1)
    8.6 (2.6 to 166.9)
    6.8 (2.2 to 44.9)
    10.9 (3.3 to 52.1)
        VCAM-1
    1387033.6 (609223.2 to 8424222.9)
    1478356.8 (642372.6 to 3859375.8)
    1058453.9 (634769.7 to 2864040.2)
    1367940.7 (721050.0 to 5184238.4)
    No statistical analyses for this end point

    Secondary: Pharmacodynamics: Peak Level of Cytokines (IP-10, Granzyme B, IFN-gamma, IL-1 RA, IL-10, IL-15, IL-2, IL-6, IL-7, IL-8, TNF alpha, and GM-CSF) in Serum (Phase 2 Cohorts 4, 5, and 6)

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    End point title
    Pharmacodynamics: Peak Level of Cytokines (IP-10, Granzyme B, IFN-gamma, IL-1 RA, IL-10, IL-15, IL-2, IL-6, IL-7, IL-8, TNF alpha, and GM-CSF) in Serum (Phase 2 Cohorts 4, 5, and 6) [23]
    End point description
    Peak was defined as the maximum post-baseline level of the cytokine. Following key cytokines were measured: IP-10, granzyme B, IFN-gamma, IL-1 RA, IL-2, IL-6, IL-7, IL-8, IL-10, IL-15, TNF alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Participants in the Safety Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 3
    Notes
    [23] - 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: The data has been reported only for the specified arms for which participants were available and data was evaluable for the specified outcome measure.
    End point values
    Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    41
    50
    40
    Units: pg/mL
    median (full range (min-max))
        IP-10
    1549.70 (469.20 to 2000.00)
    1746.15 (349.80 to 2000.00)
    1560.03 (347.00 to 2000.000)
        Granzyme B
    23.10 (1.00 to 322.60)
    27.90 (1.00 to 375.76)
    18.40 (1.00 to 162.30)
        IFN-gamma
    334.50 (24.90 to 1876.00)
    314.90 (7.50 to 1876.00)
    207.95 (18.80 to 1876.00)
        IL-1 RA (N=31, 50, 40)
    1093.70 (193.30 to 4493.10)
    908.00 (229.00 to 9000.00)
    1279.50 (227.00 to 9000.00)
        IL-2
    11.20 (0.90 to 79.40)
    11.85 (0.90 to 142.70)
    8.40 (0.90 to 277.60)
        IL-6
    136.70 (1.60 to 976.00)
    97.95 (1.60 to 976.00)
    47.25 (1.60 to 976.00)
        IL-7
    33.10 (18.00 to 67.50)
    29.80 (1.40 to 65.20)
    28.25 (13.20 to 74.30)
        IL-8
    67.40 (8.50 to 750.00)
    75.10 (5.80 to 750.00)
    52.55 (10.00 to 750.00)
        IL-10
    19.60 (1.40 to 466.00)
    14.45 (0.70 to 300.90)
    13.30 (0.70 to 171.20)
        IL-15
    45.80 (22.30 to 272.70)
    34.15 (1.40 to 140.00)
    37.20 (9.50 to 86.30)
        TNF alpha
    5.70 (2.00 to 54.60)
    5.25 (1.40 to 33.30)
    4.80 (2.10 to 20.20)
        GM-CSF
    4.40 (1.90 to 47.00)
    2.90 (1.90 to 35.60)
    1.90 (1.90 to 47.40)
    No statistical analyses for this end point

    Secondary: Pharmacodynamics: Peak Level of Cytokines (Ferritin, ICAM-1, IL-2 R, Perforin, and VCAM-1) in Serum (Phase 2 Cohorts 4, 5, and 6)

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    End point title
    Pharmacodynamics: Peak Level of Cytokines (Ferritin, ICAM-1, IL-2 R, Perforin, and VCAM-1) in Serum (Phase 2 Cohorts 4, 5, and 6) [24]
    End point description
    Peak was defined as the maximum post-baseline level of the cytokine. Following key cytokines were measured: Ferritin, ICAM-1, IL-2 R, Perforin, and VCAM-1. Participants in the Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 3
    Notes
    [24] - 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: The data has been reported only for the specified arms for which participants were available and data was evaluable for the specified outcome measure.
    End point values
    Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    41
    50
    40
    Units: ng/mL
    median (full range (min-max))
        Ferritin
    1086.36 (95.55 to 23900)
    1516.11 (89.29 to 31600)
    903.50 (171.61 to 6555.10)
        ICAM-1
    907.97 (359.51 to 5141.64)
    636.74 (361.38 to 4835.93)
    654.81 (355.15 to 4419.09)
        IL-2 R
    10.78 (2.81 to 94.59)
    7.82 (1.36 to 83.60)
    6.43 (1.70 to 33.31)
        Perforin
    17.22 (3.88 to 44.42)
    10.85 (2.53 to 100.00)
    10.12 (1.97 to 39.62)
        VCAM-1
    1255.32 (594.51 to 3932.61)
    854.63 (476.60 to 6501.14)
    836.04 (411.93 to 5079.25)
    No statistical analyses for this end point

    Secondary: Pharmacodynamics: Peak Level of Cytokine (CRP) in Serum

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    End point title
    Pharmacodynamics: Peak Level of Cytokine (CRP) in Serum
    End point description
    Peak was defined as the maximum post-baseline level of the cytokine. Participants in the Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 3
    End point values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    7
    77
    24
    38
    41
    50
    40
    Units: mg/mL
        median (full range (min-max))
    112.6 (14.6 to 655.0)
    215.7 (31.0 to 496.0)
    186.6 (18.5 to 496.0)
    137.8 (2.1 to 496.0)
    126.53 (18.19 to 496.00)
    74.84 (1.81 to 496.00)
    76.11 (7.31 to 496.00)
    No statistical analyses for this end point

    Secondary: Pharmacodynamics: Peak Level of Cytokine (Ferritin) in Serum (Phase 1 and Phase 2 Cohorts 1 and 2)

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    End point title
    Pharmacodynamics: Peak Level of Cytokine (Ferritin) in Serum (Phase 1 and Phase 2 Cohorts 1 and 2) [25]
    End point description
    Peak was defined as the maximum post-baseline level of the cytokine. Participants in the Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 3
    Notes
    [25] - 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: The data has been reported only for the specified arms for which participants were available and data was evaluable for the specified outcome measure.
    End point values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2
    Number of subjects analysed
    7
    77
    24
    Units: pg/mL
        median (full range (min-max))
    1973400.0 (1201900.0 to 32984400.0)
    3681400.0 (780.0 to 25000000.0)
    1979360.0 (780.0 to 25000000.0)
    No statistical analyses for this end point

    Secondary: Pharmacodynamics: Peak Level of Cytokine (Ferritin) in Serum (Phase 2 Cohort 3)

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    End point title
    Pharmacodynamics: Peak Level of Cytokine (Ferritin) in Serum (Phase 2 Cohort 3) [26]
    End point description
    Peak was defined as the maximum post-baseline level of the cytokine. Participants in the Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline up to Month 3
    Notes
    [26] - 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: The data has been reported only for the specified arms for which participants were available and data was evaluable for the specified outcome measure.
    End point values
    Phase 2 (Safety Management Study): Cohort 3
    Number of subjects analysed
    38
    Units: ng/mL
        median (full range (min-max))
    2440.2 (0.8 to 25000.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Positive Replication Competent Retrovirus (RCR)

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    End point title
    Percentage of Participants With Positive Replication Competent Retrovirus (RCR)
    End point description
    RCR was analyzed in blood samples by central laboratory. Because axicabtagene ciloleucel comprised retroviral vector transduced T cells, the presence of RCR in the blood of treated participants was reported. Participants in the Safety Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Day 0 (pre-infusion) up to last follow-up visit (maximum duration: 7.7, 6.8, 5.4, 4.4, 4.1 years for Phase 1 and Phase 2 Cohorts 1, 2, 3, 4, 5, and 6 respectively)
    End point values
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    7
    77
    24
    38
    41
    50
    40
    Units: percentage of participants
        number (not applicable)
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Phase 2 Safety Management Study: Number of Participants With the European Quality of Life Five Dimension Five Level Scale (EQ-5D) Score

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    End point title
    Phase 2 Safety Management Study: Number of Participants With the European Quality of Life Five Dimension Five Level Scale (EQ-5D) Score [27]
    End point description
    EQ-5D is a self-reported questionnaire used for assessing the overall health status of a participant scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was divided into 5 levels of severity: “No problem”, “Slight problems”, “Moderate problems”, “Severe problems”, and “Extreme problems (unable to perform)”. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Participants in Safety Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Month 3, and Month 6
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data has been reported only for the specified arms for which participants were available and data was evaluable for the specified outcome measure.
    End point values
    Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    38
    39
    47
    34
    Units: participants
        Baseline: Mobility : No problem
    30
    25
    33
    26
        Baseline: Mobility : Slight problem
    7
    9
    5
    4
        Baseline: Mobility : Moderate problem
    1
    5
    7
    3
        Baseline: Mobility : Severe problem
    0
    0
    1
    1
        Baseline: Mobility : Unable to perform
    0
    0
    1
    0
        Wk 4: Mobility : No problem N=32,37,38,29
    16
    21
    23
    20
        Wk 4: Mobility : Slight problem N=32,37,38,29
    11
    7
    9
    5
        Wk 4: Mobility : Moderate problem N=32,37,38,29
    4
    5
    4
    4
        Wk 4: Mobility : Severe problem N=32,37,38,29
    0
    3
    1
    0
        Wk 4: Mobility : Unable to perform N=32,37,38,29
    1
    1
    1
    0
        Month 3: Mobility : No problem N=23,31,33,29
    14
    20
    21
    22
        Month 3: Mobility : Slight problem N=23,31,33,29
    6
    8
    6
    3
        Month 3: Mobility : Moderate problem N=23,31,33,29
    2
    2
    6
    3
        Month 3: Mobility : Severe problem N=23,31,33,29
    1
    1
    0
    1
        Mon 3: Mobility : Unable to perform N=23,31,33,29
    0
    0
    0
    0
        Month 6: Mobility : No problem N=18,25,17,27
    10
    19
    11
    15
        Month 6: Mobility : Slight problem N=18,25,17,27
    6
    4
    2
    8
        Month 6: Mobility : Moderate problem N=18,25,17,27
    2
    2
    4
    3
        Month 6: Mobility : Severe problem N=18,25,17,27
    0
    0
    0
    1
        Mon 6: Mobility : Unable to perform N=18,25,17,27
    0
    0
    0
    0
        Baseline: Self-care : No problem
    37
    38
    44
    32
        Baseline: Self-care : Slight problem
    1
    1
    3
    1
        Baseline: Self-care : Moderate problem
    0
    0
    0
    1
        Baseline: Self-care : Severe problem
    0
    0
    0
    0
        Baseline: Self-care : Unable to perform
    0
    0
    0
    0
        Wk 4: Self-care : No problem N=32,37,38,29
    25
    33
    31
    24
        Wk 4: Self-care : Slight problem N=32,37,38,29
    5
    3
    6
    3
        Wk 4: Self-care : Moderate problem N=32,37,38,29
    1
    0
    1
    1
        Wk 4: Self-care : Severe problem N=32,37,38,29
    0
    1
    0
    1
        Wk 4: Self-care : Unable to perform N=32,37,38,29
    1
    0
    0
    0
        Month 3: Self-care : No problem N=23,31,33,29
    19
    29
    32
    25
        Month 3: Self-care : Slight problem N=23,31,33,29
    4
    2
    1
    4
        Mon 3: Self-care : Moderate problem N=23,31,33,29
    0
    0
    0
    0
        Month 3: Self-care : Severe problem N=23,31,33,29
    0
    0
    0
    0
        Mon 3: Self-care : Unable to perform N=23,31,33,29
    0
    0
    0
    0
        Month 6: Self-care : No problem N=18,25,17,27
    17
    25
    16
    20
        Month 6: Self-care : Slight problem N=18,25,17,27
    1
    0
    1
    7
        Mon 6: Self-care : Moderate problem N=18,25,17,27
    0
    0
    0
    0
        Month 6: Self-care : Severe problem N=18,25,17,27
    0
    0
    0
    0
        Mon 6: Self-care : Unable to perform N=18,25,17,27
    0
    0
    0
    0
        Baseline: Usual activities : No problem
    22
    22
    24
    16
        Baseline: Usual activities : Slight problem
    10
    6
    13
    14
        Baseline: Usual activities : Moderate problem
    4
    8
    8
    2
        Baseline: Usual activities : Severe problem
    2
    1
    1
    2
        Baseline: Usual activities : Unable to perform
    0
    2
    1
    0
        Wk 4: Usual activities : No problem N=32,37,37,29
    6
    12
    12
    12
        Wk 4: Usu act : Slight problem N=32,37,37,29
    13
    11
    13
    11
        Wk 4: Usu act : Moderate problem N=32,37,37,29
    11
    8
    8
    4
        Wk 4: Usu act : Severe problem N=32,37,37,29
    0
    3
    2
    1
        Wk 4: Usu act : Unable to perform N=32,37,37,29
    2
    3
    2
    1
        Mon 3: Usual activities : No problem N=23,31,33,29
    8
    16
    19
    12
        Mon 3: Usu act : Slight problem N=23,31,33,29
    9
    9
    10
    14
        Mon 3: Usu act : Moderate problem N=23,31,33,29
    5
    5
    2
    2
        Mon 3: Usu act : Severe problem N=23,31,33,29
    1
    1
    1
    1
        Mon 3: Usu act : Unable to perform N=23,31,33,29
    0
    0
    1
    0
        Mon 6: Usual activities : No problem N=18,25,17,27
    9
    15
    10
    11
        Mon 6: Usu act : Slight problem N=18,25,17,27
    5
    7
    4
    12
        Mon 6: Usu act : Moderate problem N=18,25,17,27
    3
    3
    2
    3
        Mon 6: Usu act : Severe problem N=18,25,17,27
    1
    0
    1
    0
        Mon 6: Usu act : Unable to perform N=18,25,17,27
    0
    0
    0
    1
        Baseline: Pain/Discomfort : No problem
    18
    17
    16
    15
        Baseline: Pain/Discomfort : Slight problem
    9
    17
    18
    14
        Baseline: Pain/Discomfort : Moderate problem
    8
    5
    7
    4
        Baseline: Pain/Discomfort : Severe problem
    1
    0
    5
    1
        Baseline: Pain/Discomfort : Unable to perform
    2
    0
    1
    0
        Wk 4: Pain/Discomfort : No problem N=32,37,37,29
    12
    19
    20
    17
        Wk 4: Pai : Slight problem N=32,37,37,29
    12
    13
    10
    9
        Wk 4: Pai : Moderate problem N=32,37,37,29
    7
    2
    5
    3
        Wk 4: Pai : Severe problem N=32,37,37,29
    1
    3
    2
    0
        Wk 4: Pai : Unable to perform N=32,37,37,29
    0
    0
    0
    0
        Mon 3: Pain/Discomfort : No problem N=23,31,33,29
    9
    10
    18
    16
        Mon 3: Pai : Slight problem N=23,31,33,29
    5
    14
    9
    5
        Mon 3: Pai : Moderate problem N=23,31,33,29
    9
    6
    6
    5
        Mon 3: Pai : Severe problem N=23,31,33,29
    0
    1
    0
    3
        Mon 3: Pai : Unable to perform N=23,31,33,29
    0
    0
    0
    0
        Mon 6: Pain/Discomfort : No problem N=17,25,17,27
    8
    9
    6
    12
        Mon 6: Pai : Slight problem N=17,25,17,27
    4
    14
    8
    8
        Mon 6: Pai : Moderate problem N=17,25,17,27
    5
    1
    3
    4
        Mon 6: Pai : Severe problem N=17,25,17,27
    0
    1
    0
    3
        Mon 6: Pai : Unable to perform N=17,25,17,27
    0
    0
    0
    0
        Baseline: Anxiety/Depression : No problem
    16
    23
    18
    21
        Baseline: Anxiety/Depression : Slight problem
    16
    13
    17
    9
        Baseline: Anxiety/Depression : Moderate problem
    3
    3
    10
    3
        Baseline: Anxiety/Depression : Severe problem
    1
    0
    1
    1
        Baseline: Anxiety/Depression : Unable to perform
    2
    0
    1
    0
        Wk 4: Anx : No problem N=32,37,38,29
    9
    25
    21
    23
        Wk 4: Anx : Slight problem N=32,37,38,29
    15
    8
    12
    3
        Wk 4: Anx : Moderate problem N=32,37,38,29
    7
    3
    5
    3
        Wk 4: Anx : Severe problem N=32,37,38,29
    1
    1
    0
    0
        Wk 4: Anx : Unable to perform N=32,37,38,29
    0
    0
    0
    0
        Mon 3: Anx : No problem N=23,31,33,29
    11
    19
    16
    19
        Mon 3: Anx : Slight problem N=23,31,33,29
    5
    8
    12
    7
        Mon 3: Anx : Moderate problem N=23,31,33,29
    6
    4
    4
    2
        Mon 3: Anx : Severe problem N=23,31,33,29
    1
    0
    1
    1
        Mon 3: Anx : Unable to perform N=23,31,33,29
    0
    0
    0
    0
        Mon 6: Anx : No problem N=18,25,17,26
    9
    14
    7
    18
        Mon 6: Anx : Slight problem N=18,25,17,26
    5
    10
    8
    5
        Mon 6: Anx : Moderate problem N=18,25,17,26
    3
    0
    1
    3
        Mon 6: Anx : Severe problem N=18,25,17,26
    0
    1
    1
    0
        Mon 6: Anx : Unable to perform N=18,25,17,26
    1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Phase 2 Safety Management Study: EQ-5D Visual Analogue Scale (VAS) Score

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    End point title
    Phase 2 Safety Management Study: EQ-5D Visual Analogue Scale (VAS) Score [28]
    End point description
    EQ-5D is a self-reported questionnaire used for assessing the overall health status of a participant. The EQ-5D-VAS records the participant's self-rated health on a vertical visual analogue scale and is asked to make a global assessment of their current state of health with 0 indicating the worst health they can imagine and 100 indicating the best health they can imagine. Participants in Safety Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Month 3, and Month 6
    Notes
    [28] - 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: As the endpoint was focused on only the arms under Phase 2 of the study, all the arms in the baseline period were not included.
    End point values
    Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Phase 2 (Safety Management Study): Cohort 6
    Number of subjects analysed
    38
    38
    47
    34
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    71.2 ( 21.3 )
    69.5 ( 18.8 )
    66.7 ( 20.7 )
    70.9 ( 17.0 )
        Wk 4 N=32,36,38,29
    67.8 ( 15.6 )
    67.2 ( 20.9 )
    70.8 ( 14.8 )
    76.1 ( 13.2 )
        Month 3 N=23,31,33,29
    74.9 ( 16.6 )
    78.8 ( 14.7 )
    73.3 ( 19.9 )
    76.5 ( 15.0 )
        Month 6 N=18,25,17,27
    77.1 ( 21.4 )
    85.1 ( 12.1 )
    77.1 ( 14.7 )
    79.8 ( 14.0 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse event:Up to 7.7years;All-cause Death:Enrollment upto last followup visit(maximum:7.7 years);Death for Participant Flow of Phase 2 Cohort 1(53) is more than deaths(49) reported here because deaths are separately given for main and retreatment arms.
    Adverse event reporting additional description
    Adverse events:The Safety Analysis Set included participants treated with any dose of axicabtageneciloleucel;Retreatment groups:The Safety-Retreatment Analysis Set included participants re-treated of axicabtageneciloleucel.All-cause mortality:All Enrolled Analysis Set included enrolled participants,Retreatment group:Safety-Retreatment Analysis Set.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot
    Reporting group description
    Participants with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) received conditioning chemotherapy (fludarabine 30 mg/m^2 intravenously [IV] over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of body weight (BW) on Day 0.

    Reporting group title
    Phase 2 (Pivotal Study): Cohort 1
    Reporting group description
    Participants with refractory DLBCL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.

    Reporting group title
    Phase 2 (Pivotal Study): Cohort 2
    Reporting group description
    Participants with refractory PMBCL or TFL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 3
    Reporting group description
    Participants with relapsed or refractory transplant ineligible DLBCL, PMBCL, or TFL received conditioning chemotherapy (fludarabine 30 mg/m^2 IV over 30 minutes and cyclophosphamide 500 mg/m^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants also received a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0) and tocilizumab (8 mg/kg IV over 1 hour (not to exceed 800 mg)) on Day 2).

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 4
    Reporting group description
    Participants with r/r DLBCL,PMBCL,TFL,or high-grade B-cell lymphoma(HGBCL)after 2 systemic lines of therapy will receive optional bridging therapy(dexamethasone 20mg to 40mg,eitherorally or IV daily for 1 to 4 days or 1g/m^2 of high-dose methylprednisolone(HDMP)for 3 days with rituximab at 375mg/m^2 weekly for 3 weeks or bendamustine 90 mg/m^2 on Days 1 and 2 and rituximab 375mg/m^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3;followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW. Participants will receive a prophylactic regimen of levetiracetam(750 mg orally or IV twice daily(BID)starting on Day 0).Participants received tocilizumab(initiated on persistent Grade 1 cytokine release syndrome(CRS)for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 5
    Reporting group description
    Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy received debulking therapy (R-CHOP:rituximab 375mg/m^2 D1,doxorubicin 50mg/m^2 D1,prednisone 100mg D1 to D5,cyclophosphamide 750mg/m^2 D1,vincristine 1.4 mg/m^2 D1 or R-ICE:rituximab 375mg/ m^2 D1,ifosfamide 5g/m^2 24h-CI D2,carboplatin AUC5 D2 maximum dose 800mg,etoposide 100 mg/m^2/day D1 to D3 or R-GEMOX:rituximab 375mg/m^2 D1,gemcitabine 1000mg/m^2 D2,oxaliplatin 100mg/m^2 D2 or R-GDP:rituximab 375mg/m^2 D1 or D8,gemcitabine 1g/m^2 D1 & D8,dexamethasone 40mg D1 to D4,cisplatin 75mg/m^2 D1(or carboplatin AUC5 D1) or radiotherapy:20 to 30 Gy), conditioning chemotherapy (fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants also received a prophylactic regimen of levetiracetam (750 mg orally or IV BID starting on D0).D=Day.

    Reporting group title
    Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 5
    Reporting group description
    Participants who initially responded and subsequently relapsed, became eligible for second course of conditioning chemotherapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose.

    Reporting group title
    Retreatment Axicabtagene Ciloleucel: Phase 1
    Reporting group description
    Participants who initially responded and subsequently relapsed, became eligible for second course of conditioning chemotherapy and axicabtagene ciloleucel. Participants received the axicabtagene ciloleucel regimen selected for Phase 2.

    Reporting group title
    Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 1
    Reporting group description
    Participants who initially responded and subsequently relapsed, became eligible for second course of conditioning chemotherapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose.

    Reporting group title
    Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 2
    Reporting group description
    Participants who initially responded and subsequently relapsed, became eligible for second course of conditioning chemotherapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose.

    Reporting group title
    Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 3
    Reporting group description
    Participants who initially responded and subsequently relapsed, became eligible for second course of conditioning chemotherapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose.

    Reporting group title
    Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 4
    Reporting group description
    Participants who initially responded and subsequently relapsed, became eligible for second course of conditioning chemotherapy and axicabtagene ciloleucel. Participants received the same axicabtagene ciloleucel regimen as the original target dose.

    Reporting group title
    Phase 2 (Safety Management Study): Cohort 6
    Reporting group description
    Participants with r/r DLBCL,PMBCL,TFL orHGBCL after 2 systemic lines of therapy may receive bridging therapy(dexamethasone 20mg to 40mg,orally or IV daily for 1 to 4 days or 1g/m^2 HDMP for 3 days with rituximab at 375mg/m^2 weekly for 3 weeks or bendamustine 90 mg/m^2 on Days 1 and 2 and rituximab 375mg/m^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m^2 IV and cyclophosphamide 500mg/m^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of BW on Day 0.Participants will also receive a prophylactic regimen of levetiracetam 750 mg orally or IV twice daily(BID)starting on Day 0)and corticosteroids(dexamethasone, 10 mg once daily on Days 0, 1, and 2).Participants received tocilizumab(initiated on persistent Grade 1 CRS for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity).

    Serious adverse events
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 5 Retreatment Axicabtagene Ciloleucel: Phase 1 Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 1 Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 2 Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 3 Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 4 Phase 2 (Safety Management Study): Cohort 6
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 7 (71.43%)
    40 / 77 (51.95%)
    14 / 24 (58.33%)
    26 / 38 (68.42%)
    24 / 41 (58.54%)
    27 / 50 (54.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    5 / 9 (55.56%)
    1 / 2 (50.00%)
    2 / 2 (100.00%)
    0 / 2 (0.00%)
    25 / 40 (62.50%)
         number of deaths (all causes)
    5
    49
    13
    23
    20
    37
    2
    1
    8
    2
    1
    2
    20
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-cell lymphoma
         subjects affected / exposed
    1 / 7 (14.29%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    3 / 38 (7.89%)
    3 / 41 (7.32%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 9 (22.22%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
    0 / 3
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    0 / 0
    0 / 3
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    2 / 24 (8.33%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    1 / 2
    0 / 0
    0 / 2
    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 / 1
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diffuse large B-cell lymphoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carcinoma in situ
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Central nervous system lymphoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    1 / 24 (4.17%)
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 2
    3 / 4
    2 / 2
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Gait disturbance
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    1 / 24 (4.17%)
    3 / 38 (7.89%)
    2 / 41 (4.88%)
    5 / 50 (10.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    4 / 40 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 5
    0 / 1
    1 / 4
    2 / 2
    3 / 5
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health ~ deterioration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
    0 / 0
    1 / 2
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Acute respiratory failure
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspiration
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary ~ disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reexpansion pulmonary oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    2 / 24 (8.33%)
    3 / 38 (7.89%)
    1 / 41 (2.44%)
    5 / 50 (10.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    5 / 40 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    3 / 3
    3 / 3
    1 / 1
    4 / 5
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Agitation
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    2 / 24 (8.33%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Restlessness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Troponin T increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Hip fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain herniation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    2 / 24 (8.33%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    3 / 41 (7.32%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    2 / 2
    3 / 3
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 7 (14.29%)
    16 / 77 (20.78%)
    3 / 24 (12.50%)
    9 / 38 (23.68%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    17 / 17
    5 / 5
    10 / 10
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    1 / 1
    2 / 2
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    4 / 50 (8.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    4 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune effector cell-associated ~ neurotoxicity syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    2 / 41 (4.88%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    2 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysgraphia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukoencephalopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Presyncope
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Apraxia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain injury
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral venous sinus thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disturbance in attention
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspraxia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Memory impairment
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine with aura
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic encephalopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Seizure like phenomena
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Quadriplegia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    1 / 7 (14.29%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 5
    0 / 0
    0 / 2
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    2 / 41 (4.88%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    2 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Visual impairment
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tongue ulceration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Toxic skin eruption
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anuria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amyotrophy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 7 (28.57%)
    7 / 77 (9.09%)
    3 / 24 (12.50%)
    1 / 38 (2.63%)
    3 / 41 (7.32%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 9
    1 / 3
    1 / 1
    2 / 3
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Covid-19
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Covid-19 pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenovirus infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus enteritis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Human herpesvirus 6 encephalitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Klebsiella infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal sepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia necrotising
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial ~ viral
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotavirus infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract ~ infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acidosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemot Phase 2 (Pivotal Study): Cohort 1 Phase 2 (Pivotal Study): Cohort 2 Phase 2 (Safety Management Study): Cohort 3 Phase 2 (Safety Management Study): Cohort 4 Phase 2 (Safety Management Study): Cohort 5 Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 5 Retreatment Axicabtagene Ciloleucel: Phase 1 Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 1 Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 2 Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 3 Retreatment Axicabtagene Ciloleucel: Phase 2 Cohort 4 Phase 2 (Safety Management Study): Cohort 6
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    77 / 77 (100.00%)
    23 / 24 (95.83%)
    38 / 38 (100.00%)
    41 / 41 (100.00%)
    50 / 50 (100.00%)
    2 / 2 (100.00%)
    1 / 1 (100.00%)
    9 / 9 (100.00%)
    2 / 2 (100.00%)
    2 / 2 (100.00%)
    2 / 2 (100.00%)
    40 / 40 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    0
    0
    0
    0
    0
    1
    0
    Cancer pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    3 / 7 (42.86%)
    44 / 77 (57.14%)
    14 / 24 (58.33%)
    22 / 38 (57.89%)
    24 / 41 (58.54%)
    25 / 50 (50.00%)
    1 / 2 (50.00%)
    1 / 1 (100.00%)
    1 / 9 (11.11%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    21 / 40 (52.50%)
         occurrences all number
    3
    49
    22
    30
    30
    28
    1
    3
    1
    1
    0
    1
    30
    Hypertension
         subjects affected / exposed
    1 / 7 (14.29%)
    9 / 77 (11.69%)
    4 / 24 (16.67%)
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    4 / 40 (10.00%)
         occurrences all number
    1
    14
    8
    2
    2
    3
    0
    0
    0
    1
    0
    0
    8
    Capillary leak syndrome
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    2
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    2
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    3
    Hot flush
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    2
    Subclavian vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    1 / 7 (14.29%)
    32 / 77 (41.56%)
    7 / 24 (29.17%)
    11 / 38 (28.95%)
    11 / 41 (26.83%)
    14 / 50 (28.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    2 / 9 (22.22%)
    2 / 2 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    8 / 40 (20.00%)
         occurrences all number
    1
    34
    7
    16
    13
    15
    0
    1
    2
    3
    0
    0
    8
    Fatigue
         subjects affected / exposed
    2 / 7 (28.57%)
    34 / 77 (44.16%)
    12 / 24 (50.00%)
    18 / 38 (47.37%)
    19 / 41 (46.34%)
    12 / 50 (24.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 9 (33.33%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    18 / 40 (45.00%)
         occurrences all number
    3
    41
    15
    21
    20
    13
    0
    0
    3
    0
    1
    1
    25
    Pyrexia
         subjects affected / exposed
    7 / 7 (100.00%)
    66 / 77 (85.71%)
    21 / 24 (87.50%)
    35 / 38 (92.11%)
    39 / 41 (95.12%)
    40 / 50 (80.00%)
    2 / 2 (100.00%)
    1 / 1 (100.00%)
    9 / 9 (100.00%)
    2 / 2 (100.00%)
    1 / 2 (50.00%)
    2 / 2 (100.00%)
    33 / 40 (82.50%)
         occurrences all number
    9
    81
    32
    48
    49
    60
    2
    1
    13
    3
    1
    2
    41
    Asthenia
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    2 / 24 (8.33%)
    3 / 38 (7.89%)
    2 / 41 (4.88%)
    4 / 50 (8.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    5 / 40 (12.50%)
         occurrences all number
    0
    5
    2
    3
    2
    5
    0
    0
    1
    1
    0
    0
    5
    Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    1 / 24 (4.17%)
    5 / 38 (13.16%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    5
    1
    5
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Malaise
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    2 / 50 (4.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    4
    0
    1
    1
    2
    1
    0
    1
    0
    0
    0
    2
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    2 / 24 (8.33%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    5
    2
    2
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Gait disturbance
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    4 / 38 (10.53%)
    0 / 41 (0.00%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    2
    0
    4
    0
    2
    0
    0
    0
    0
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    1
    0
    0
    3
    2
    0
    2
    0
    0
    0
    0
    0
    3
    Oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    0
    0
    1
    0
    0
    1
    2
    Oedema peripheral
         subjects affected / exposed
    1 / 7 (14.29%)
    12 / 77 (15.58%)
    2 / 24 (8.33%)
    6 / 38 (15.79%)
    2 / 41 (4.88%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    1
    14
    2
    7
    2
    3
    0
    0
    1
    1
    0
    0
    3
    Chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    3 / 41 (7.32%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    1
    3
    0
    0
    0
    0
    1
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    2
    Swelling
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 77 (1.30%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    1
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Puncture site pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    Catheter site pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Hernia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    3 / 7 (42.86%)
    10 / 77 (12.99%)
    3 / 24 (12.50%)
    2 / 38 (5.26%)
    6 / 41 (14.63%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    8 / 40 (20.00%)
         occurrences all number
    3
    10
    3
    2
    6
    1
    0
    0
    0
    0
    0
    2
    11
    Graft versus host disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    2
    0
    0
    0
    Reproductive system and breast disorders
    Scrotal oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Perineal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia
         subjects affected / exposed
    4 / 7 (57.14%)
    24 / 77 (31.17%)
    5 / 24 (20.83%)
    9 / 38 (23.68%)
    6 / 41 (14.63%)
    5 / 50 (10.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 9 (22.22%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    7 / 40 (17.50%)
         occurrences all number
    5
    27
    5
    10
    6
    5
    0
    0
    2
    2
    0
    1
    8
    Cough
         subjects affected / exposed
    2 / 7 (28.57%)
    18 / 77 (23.38%)
    6 / 24 (25.00%)
    9 / 38 (23.68%)
    11 / 41 (26.83%)
    6 / 50 (12.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    5 / 9 (55.56%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    6 / 40 (15.00%)
         occurrences all number
    4
    20
    12
    11
    12
    6
    0
    0
    5
    0
    0
    0
    8
    Nasal congestion
         subjects affected / exposed
    1 / 7 (14.29%)
    4 / 77 (5.19%)
    1 / 24 (4.17%)
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    4 / 40 (10.00%)
         occurrences all number
    2
    4
    1
    2
    1
    0
    0
    0
    0
    1
    0
    0
    4
    Oropharyngeal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    4 / 77 (5.19%)
    2 / 24 (8.33%)
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    1
    5
    2
    2
    1
    2
    0
    0
    0
    1
    0
    0
    2
    Pleural effusion
         subjects affected / exposed
    3 / 7 (42.86%)
    9 / 77 (11.69%)
    1 / 24 (4.17%)
    5 / 38 (13.16%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    3
    9
    1
    5
    3
    0
    0
    0
    0
    1
    0
    0
    0
    Dyspnoea
         subjects affected / exposed
    3 / 7 (42.86%)
    11 / 77 (14.29%)
    4 / 24 (16.67%)
    5 / 38 (13.16%)
    3 / 41 (7.32%)
    4 / 50 (8.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    8 / 40 (20.00%)
         occurrences all number
    4
    11
    5
    5
    3
    5
    0
    0
    0
    1
    0
    0
    12
    Wheezing
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    4
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Pulmonary oedema
         subjects affected / exposed
    2 / 7 (28.57%)
    5 / 77 (6.49%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    2
    6
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Upper-airway cough syndrome
         subjects affected / exposed
    1 / 7 (14.29%)
    4 / 77 (5.19%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    4
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tachypnoea
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    1 / 24 (4.17%)
    3 / 38 (7.89%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    2
    1
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hiccups
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    3
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    5
    Laryngeal haemorrhage
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    Atelectasis
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    2
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Paranasal cyst
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 7 (0.00%)
    9 / 77 (11.69%)
    3 / 24 (12.50%)
    4 / 38 (10.53%)
    0 / 41 (0.00%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 9 (22.22%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    4 / 40 (10.00%)
         occurrences all number
    0
    9
    3
    4
    0
    2
    0
    0
    2
    0
    0
    0
    5
    Insomnia
         subjects affected / exposed
    1 / 7 (14.29%)
    7 / 77 (9.09%)
    2 / 24 (8.33%)
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    3 / 9 (33.33%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    6 / 40 (15.00%)
         occurrences all number
    1
    7
    4
    4
    2
    0
    0
    1
    3
    1
    1
    0
    6
    Confusional state
         subjects affected / exposed
    1 / 7 (14.29%)
    19 / 77 (24.68%)
    8 / 24 (33.33%)
    16 / 38 (42.11%)
    4 / 41 (9.76%)
    6 / 50 (12.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 9 (22.22%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    12 / 40 (30.00%)
         occurrences all number
    1
    20
    10
    19
    6
    8
    0
    0
    2
    1
    0
    0
    14
    Agitation
         subjects affected / exposed
    1 / 7 (14.29%)
    5 / 77 (6.49%)
    3 / 24 (12.50%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    1
    6
    3
    0
    1
    0
    0
    0
    0
    0
    0
    0
    4
    Hallucination
         subjects affected / exposed
    1 / 7 (14.29%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    1
    4
    0
    1
    2
    0
    0
    0
    0
    0
    0
    0
    1
    Mental status changes
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 77 (5.19%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    4
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Delirium
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    1
    2
    0
    2
    0
    2
    0
    0
    0
    0
    0
    0
    1
    Bradyphrenia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Disorientation
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    1
    1
    1
    0
    0
    0
    0
    2
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    3
    Restlessness
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 77 (2.60%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    1
    2
    1
    1
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Mood altered
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Investigations
    White blood cell count decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    23 / 77 (29.87%)
    8 / 24 (33.33%)
    10 / 38 (26.32%)
    6 / 41 (14.63%)
    14 / 50 (28.00%)
    1 / 2 (50.00%)
    1 / 1 (100.00%)
    3 / 9 (33.33%)
    2 / 2 (100.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    10 / 40 (25.00%)
         occurrences all number
    7
    63
    15
    13
    13
    24
    1
    1
    9
    6
    0
    2
    24
    Platelet count decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    25 / 77 (32.47%)
    5 / 24 (20.83%)
    9 / 38 (23.68%)
    10 / 41 (24.39%)
    17 / 50 (34.00%)
    1 / 2 (50.00%)
    1 / 1 (100.00%)
    3 / 9 (33.33%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    6 / 40 (15.00%)
         occurrences all number
    6
    46
    10
    16
    17
    20
    1
    1
    8
    2
    0
    1
    6
    Neutrophil count decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    27 / 77 (35.06%)
    7 / 24 (29.17%)
    11 / 38 (28.95%)
    13 / 41 (31.71%)
    25 / 50 (50.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 9 (44.44%)
    2 / 2 (100.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    14 / 40 (35.00%)
         occurrences all number
    9
    63
    16
    18
    29
    49
    0
    0
    11
    2
    0
    2
    25
    Lymphocyte count decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    12 / 77 (15.58%)
    6 / 24 (25.00%)
    4 / 38 (10.53%)
    4 / 41 (9.76%)
    8 / 50 (16.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    3 / 9 (33.33%)
    2 / 2 (100.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    7 / 40 (17.50%)
         occurrences all number
    2
    24
    9
    4
    4
    12
    0
    3
    8
    2
    0
    1
    11
    C-reactive protein increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    5 / 41 (12.20%)
    7 / 50 (14.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    0
    2
    6
    7
    0
    0
    0
    0
    0
    1
    1
    Weight decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    11 / 77 (14.29%)
    4 / 24 (16.67%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    4 / 50 (8.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 9 (22.22%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    3
    18
    9
    1
    0
    4
    0
    0
    6
    2
    0
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 7 (28.57%)
    11 / 77 (14.29%)
    5 / 24 (20.83%)
    7 / 38 (18.42%)
    4 / 41 (9.76%)
    7 / 50 (14.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    2
    14
    7
    10
    4
    9
    0
    0
    0
    0
    0
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 7 (42.86%)
    13 / 77 (16.88%)
    5 / 24 (20.83%)
    8 / 38 (21.05%)
    5 / 41 (12.20%)
    7 / 50 (14.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    3
    14
    8
    12
    6
    8
    0
    0
    1
    1
    0
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 77 (5.19%)
    2 / 24 (8.33%)
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    5
    2
    0
    3
    1
    0
    0
    0
    0
    0
    1
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 77 (3.90%)
    1 / 24 (4.17%)
    4 / 38 (10.53%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    3
    3
    4
    1
    1
    0
    0
    2
    0
    0
    0
    0
    Serum ferritin increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    1 / 24 (4.17%)
    2 / 38 (5.26%)
    3 / 41 (7.32%)
    5 / 50 (10.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    1
    1
    2
    3
    5
    0
    0
    0
    0
    0
    0
    1
    Weight increased
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    4 / 41 (9.76%)
    4 / 50 (8.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    6
    0
    1
    4
    4
    0
    0
    1
    0
    0
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    1 / 24 (4.17%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    4
    1
    5
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    4 / 50 (8.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    5
    6
    0
    0
    0
    0
    0
    0
    0
    Blood immunoglobulin G decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    3
    0
    1
    0
    3
    0
    0
    0
    0
    0
    0
    0
    Blood potassium decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    4 / 50 (8.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    6
    0
    0
    0
    0
    0
    0
    0
    Urine output decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    Immunoglobulins decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    Blood fibrinogen decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    0
    5
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    0
    Blood albumin decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood magnesium decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Skin abrasion
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Infusion related reaction
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 77 (1.30%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Fall
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    2 / 24 (8.33%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    5
    2
    0
    0
    1
    0
    0
    0
    0
    0
    0
    4
    Head injury
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Procedural pain
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    5
    1
    1
    1
    2
    0
    0
    0
    0
    0
    0
    1
    Sinus bradycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    2 / 24 (8.33%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    5
    8
    1
    1
    0
    0
    0
    0
    1
    0
    0
    1
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 77 (3.90%)
    2 / 24 (8.33%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    3
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    19 / 77 (24.68%)
    2 / 24 (8.33%)
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 9 (44.44%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    5 / 40 (12.50%)
         occurrences all number
    0
    25
    11
    5
    2
    3
    0
    0
    11
    1
    0
    0
    6
    Tachycardia
         subjects affected / exposed
    3 / 7 (42.86%)
    29 / 77 (37.66%)
    8 / 24 (33.33%)
    6 / 38 (15.79%)
    7 / 41 (17.07%)
    7 / 50 (14.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    6 / 40 (15.00%)
         occurrences all number
    3
    35
    9
    7
    8
    8
    0
    0
    1
    0
    0
    0
    8
    Bradycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    4
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Acute left ventricular failure
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    4
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    Tremor
         subjects affected / exposed
    4 / 7 (57.14%)
    23 / 77 (29.87%)
    6 / 24 (25.00%)
    16 / 38 (42.11%)
    5 / 41 (12.20%)
    11 / 50 (22.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 9 (44.44%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    9 / 40 (22.50%)
         occurrences all number
    4
    23
    7
    16
    5
    12
    0
    0
    5
    1
    0
    0
    12
    Headache
         subjects affected / exposed
    3 / 7 (42.86%)
    34 / 77 (44.16%)
    12 / 24 (50.00%)
    19 / 38 (50.00%)
    16 / 41 (39.02%)
    17 / 50 (34.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    3 / 9 (33.33%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    2 / 2 (100.00%)
    13 / 40 (32.50%)
         occurrences all number
    4
    39
    14
    21
    20
    20
    2
    0
    4
    2
    0
    4
    16
    Encephalopathy
         subjects affected / exposed
    4 / 7 (57.14%)
    20 / 77 (25.97%)
    6 / 24 (25.00%)
    9 / 38 (23.68%)
    5 / 41 (12.20%)
    5 / 50 (10.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 9 (22.22%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    5
    22
    7
    10
    6
    5
    0
    0
    2
    0
    0
    0
    4
    Dysarthria
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    1 / 24 (4.17%)
    3 / 38 (7.89%)
    2 / 41 (4.88%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    3
    1
    3
    4
    1
    0
    0
    0
    0
    0
    0
    2
    Somnolence
         subjects affected / exposed
    3 / 7 (42.86%)
    10 / 77 (12.99%)
    4 / 24 (16.67%)
    3 / 38 (7.89%)
    5 / 41 (12.20%)
    5 / 50 (10.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    5 / 40 (12.50%)
         occurrences all number
    3
    12
    5
    6
    5
    5
    0
    0
    1
    1
    0
    0
    5
    Aphasia
         subjects affected / exposed
    1 / 7 (14.29%)
    13 / 77 (16.88%)
    4 / 24 (16.67%)
    8 / 38 (21.05%)
    4 / 41 (9.76%)
    9 / 50 (18.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    4 / 40 (10.00%)
         occurrences all number
    1
    14
    5
    10
    4
    9
    0
    0
    0
    1
    0
    1
    4
    Dizziness
         subjects affected / exposed
    1 / 7 (14.29%)
    12 / 77 (15.58%)
    9 / 24 (37.50%)
    5 / 38 (13.16%)
    7 / 41 (17.07%)
    8 / 50 (16.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    6 / 40 (15.00%)
         occurrences all number
    1
    13
    10
    6
    8
    9
    2
    0
    1
    1
    0
    0
    7
    Memory impairment
         subjects affected / exposed
    0 / 7 (0.00%)
    6 / 77 (7.79%)
    2 / 24 (8.33%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    6
    2
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    0
    5
    3
    1
    0
    0
    0
    0
    0
    0
    2
    Dysgeusia
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    2 / 24 (8.33%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    5
    2
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    Dyskinesia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Dysgraphia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    1
    Seizure
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 77 (3.90%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    6
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Disturbance in attention
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    2 / 24 (8.33%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    1
    3
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Post herpetic neuralgia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Head discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Dementia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Apraxia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    2
    Muscle contractions involuntary
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Poor sucking reflex
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Sensory loss
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 7 (57.14%)
    47 / 77 (61.04%)
    13 / 24 (54.17%)
    22 / 38 (57.89%)
    19 / 41 (46.34%)
    19 / 50 (38.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    3 / 9 (33.33%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    13 / 40 (32.50%)
         occurrences all number
    7
    75
    20
    34
    27
    47
    0
    1
    9
    1
    0
    1
    16
    Neutropenia
         subjects affected / exposed
    3 / 7 (42.86%)
    26 / 77 (33.77%)
    12 / 24 (50.00%)
    18 / 38 (47.37%)
    16 / 41 (39.02%)
    16 / 50 (32.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    20 / 40 (50.00%)
         occurrences all number
    5
    41
    20
    30
    24
    25
    0
    0
    1
    1
    0
    0
    43
    Thrombocytopenia
         subjects affected / exposed
    2 / 7 (28.57%)
    24 / 77 (31.17%)
    6 / 24 (25.00%)
    12 / 38 (31.58%)
    7 / 41 (17.07%)
    9 / 50 (18.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    10 / 40 (25.00%)
         occurrences all number
    2
    30
    7
    21
    9
    10
    0
    0
    0
    0
    0
    0
    18
    Febrile neutropenia
         subjects affected / exposed
    4 / 7 (57.14%)
    21 / 77 (27.27%)
    8 / 24 (33.33%)
    10 / 38 (26.32%)
    3 / 41 (7.32%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 9 (33.33%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    4
    22
    9
    10
    3
    2
    0
    0
    4
    1
    0
    0
    2
    Pancytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    4 / 41 (9.76%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    1
    0
    4
    3
    0
    0
    0
    0
    0
    0
    0
    Leukopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    13 / 77 (16.88%)
    3 / 24 (12.50%)
    4 / 38 (10.53%)
    7 / 41 (17.07%)
    8 / 50 (16.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    7 / 40 (17.50%)
         occurrences all number
    0
    19
    7
    4
    14
    11
    0
    0
    0
    0
    0
    0
    15
    Lymphopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    4 / 40 (10.00%)
         occurrences all number
    0
    6
    0
    0
    7
    0
    0
    0
    0
    0
    0
    0
    6
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    1
    0
    0
    0
    0
    0
    Ear pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Hypoacusis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 77 (2.60%)
    2 / 24 (8.33%)
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    1
    2
    2
    2
    1
    1
    0
    0
    0
    0
    0
    0
    2
    Vitreous floaters
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    2
    Eyelid function disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    1 / 7 (14.29%)
    17 / 77 (22.08%)
    11 / 24 (45.83%)
    9 / 38 (23.68%)
    6 / 41 (14.63%)
    7 / 50 (14.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 2 (100.00%)
    8 / 40 (20.00%)
         occurrences all number
    1
    18
    12
    10
    8
    7
    1
    0
    1
    0
    0
    2
    9
    Constipation
         subjects affected / exposed
    2 / 7 (28.57%)
    15 / 77 (19.48%)
    5 / 24 (20.83%)
    7 / 38 (18.42%)
    6 / 41 (14.63%)
    8 / 50 (16.00%)
    1 / 2 (50.00%)
    1 / 1 (100.00%)
    3 / 9 (33.33%)
    2 / 2 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    15 / 40 (37.50%)
         occurrences all number
    3
    17
    9
    7
    6
    8
    1
    1
    3
    2
    0
    0
    19
    Nausea
         subjects affected / exposed
    1 / 7 (14.29%)
    22 / 77 (28.57%)
    12 / 24 (50.00%)
    15 / 38 (39.47%)
    12 / 41 (29.27%)
    12 / 50 (24.00%)
    2 / 2 (100.00%)
    1 / 1 (100.00%)
    4 / 9 (44.44%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    2 / 2 (100.00%)
    14 / 40 (35.00%)
         occurrences all number
    1
    27
    13
    18
    17
    14
    2
    1
    4
    0
    1
    2
    20
    Diarrhoea
         subjects affected / exposed
    5 / 7 (71.43%)
    29 / 77 (37.66%)
    8 / 24 (33.33%)
    16 / 38 (42.11%)
    25 / 41 (60.98%)
    11 / 50 (22.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 9 (22.22%)
    2 / 2 (100.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    11 / 40 (27.50%)
         occurrences all number
    5
    32
    9
    25
    29
    11
    0
    0
    2
    3
    0
    1
    14
    Abdominal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    8 / 77 (10.39%)
    3 / 24 (12.50%)
    3 / 38 (7.89%)
    2 / 41 (4.88%)
    5 / 50 (10.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    5 / 40 (12.50%)
         occurrences all number
    1
    8
    3
    3
    2
    5
    0
    0
    0
    0
    0
    0
    5
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    1
    2
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Anal incontinence
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    2 / 41 (4.88%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    1
    0
    2
    1
    0
    0
    0
    0
    0
    0
    2
    Stomatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    4 / 50 (8.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    1
    0
    2
    1
    4
    0
    0
    0
    0
    0
    0
    1
    Dry mouth
         subjects affected / exposed
    2 / 7 (28.57%)
    7 / 77 (9.09%)
    3 / 24 (12.50%)
    3 / 38 (7.89%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 9 (22.22%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    2
    7
    3
    3
    5
    0
    0
    0
    2
    0
    0
    0
    3
    Dyspepsia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    2 / 41 (4.88%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    2
    1
    0
    2
    3
    0
    0
    0
    0
    0
    0
    1
    Abdominal distension
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    2 / 24 (8.33%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    6
    2
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    1 / 24 (4.17%)
    3 / 38 (7.89%)
    1 / 41 (2.44%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    2
    1
    3
    1
    2
    0
    0
    0
    0
    0
    0
    5
    Dysphagia
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    5 / 38 (13.16%)
    3 / 41 (7.32%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    4
    0
    5
    3
    2
    0
    0
    0
    0
    0
    0
    1
    Toothache
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    1
    0
    0
    1
    Rectal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Flatulence
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 77 (3.90%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    3
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Ascites
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    2
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Odynophagia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    2
    0
    2
    2
    0
    0
    0
    0
    0
    0
    0
    2
    Rash
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    1 / 24 (4.17%)
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    2 / 50 (4.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    2
    1
    2
    1
    2
    1
    0
    1
    0
    0
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 7 (0.00%)
    6 / 77 (7.79%)
    2 / 24 (8.33%)
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    6
    2
    1
    1
    3
    0
    0
    0
    0
    0
    0
    2
    Hyperhidrosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    1
    2
    2
    2
    0
    0
    0
    0
    0
    0
    1
    Alopecia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    2
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    2
    Erythema
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    4
    Night sweats
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    0
    0
    1
    0
    0
    0
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    2 / 24 (8.33%)
    3 / 38 (7.89%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    2
    2
    3
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Pollakiuria
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    4 / 40 (10.00%)
         occurrences all number
    0
    2
    0
    2
    2
    1
    0
    0
    0
    0
    0
    0
    4
    Acute kidney injury
         subjects affected / exposed
    1 / 7 (14.29%)
    6 / 77 (7.79%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    1
    7
    0
    2
    2
    1
    0
    0
    0
    0
    0
    0
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 7 (0.00%)
    7 / 77 (9.09%)
    1 / 24 (4.17%)
    4 / 38 (10.53%)
    1 / 41 (2.44%)
    3 / 50 (6.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    7
    1
    4
    1
    3
    0
    0
    0
    0
    0
    0
    3
    Urinary retention
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    4
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    3
    Haematuria
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    4
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    2
    Urinary tract obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Bladder spasm
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    2 / 7 (28.57%)
    10 / 77 (12.99%)
    3 / 24 (12.50%)
    5 / 38 (13.16%)
    2 / 41 (4.88%)
    1 / 50 (2.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    2
    10
    3
    6
    4
    1
    1
    0
    1
    0
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    1 / 7 (14.29%)
    7 / 77 (9.09%)
    4 / 24 (16.67%)
    1 / 38 (2.63%)
    4 / 41 (9.76%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    1
    7
    4
    1
    4
    1
    0
    0
    0
    1
    0
    0
    3
    Muscular weakness
         subjects affected / exposed
    3 / 7 (42.86%)
    11 / 77 (14.29%)
    2 / 24 (8.33%)
    4 / 38 (10.53%)
    1 / 41 (2.44%)
    2 / 50 (4.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    3 / 9 (33.33%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    6 / 40 (15.00%)
         occurrences all number
    4
    11
    2
    4
    1
    2
    1
    0
    3
    1
    0
    0
    6
    Arthralgia
         subjects affected / exposed
    0 / 7 (0.00%)
    12 / 77 (15.58%)
    2 / 24 (8.33%)
    1 / 38 (2.63%)
    4 / 41 (9.76%)
    4 / 50 (8.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    9 / 40 (22.50%)
         occurrences all number
    0
    13
    2
    1
    4
    4
    0
    0
    0
    0
    0
    0
    12
    Back pain
         subjects affected / exposed
    1 / 7 (14.29%)
    13 / 77 (16.88%)
    2 / 24 (8.33%)
    1 / 38 (2.63%)
    5 / 41 (12.20%)
    4 / 50 (8.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    2 / 40 (5.00%)
         occurrences all number
    1
    14
    2
    1
    5
    4
    1
    0
    1
    0
    0
    1
    2
    Muscle spasms
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    2
    0
    3
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Flank pain
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    2
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Bone pain
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 9 (33.33%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    2
    0
    3
    1
    0
    0
    0
    3
    0
    0
    0
    2
    Neck pain
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 77 (3.90%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    2
    3
    1
    1
    2
    0
    1
    0
    0
    0
    0
    0
    2
    Tenosynovitis stenosans
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Groin pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 7 (28.57%)
    5 / 77 (6.49%)
    4 / 24 (16.67%)
    7 / 38 (18.42%)
    3 / 41 (7.32%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    3
    5
    4
    7
    3
    1
    0
    0
    0
    0
    0
    0
    4
    Herpes zoster
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 77 (3.90%)
    3 / 24 (12.50%)
    1 / 38 (2.63%)
    4 / 41 (9.76%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    2
    3
    3
    1
    5
    1
    0
    0
    0
    0
    0
    0
    1
    Sinusitis
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 77 (3.90%)
    2 / 24 (8.33%)
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    2
    3
    3
    2
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 77 (3.90%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    1
    3
    1
    0
    1
    3
    0
    0
    0
    0
    0
    0
    3
    Pneumonia
         subjects affected / exposed
    1 / 7 (14.29%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    6 / 41 (14.63%)
    4 / 50 (8.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    1
    4
    0
    1
    7
    4
    0
    0
    1
    0
    0
    0
    1
    Candida infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    1 / 24 (4.17%)
    4 / 38 (10.53%)
    0 / 41 (0.00%)
    2 / 50 (4.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    1
    4
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    2 / 40 (5.00%)
         occurrences all number
    1
    1
    0
    1
    2
    0
    0
    0
    0
    0
    0
    1
    2
    Clostridium difficile infection
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 77 (6.49%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    5
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Covid-19
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    4 / 40 (10.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    4
    Nasopharyngitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    1
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    2 / 24 (8.33%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    3
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    1 / 24 (4.17%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    2
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    2
    Tooth infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Oral herpes
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 77 (1.30%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Folliculitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 77 (2.60%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Ear infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tinea versicolour
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Wound infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    2 / 7 (28.57%)
    23 / 77 (29.87%)
    8 / 24 (33.33%)
    6 / 38 (15.79%)
    6 / 41 (14.63%)
    10 / 50 (20.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 9 (22.22%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
    11 / 40 (27.50%)
         occurrences all number
    2
    28
    11
    9
    7
    13
    0
    0
    5
    0
    0
    1
    14
    Decreased appetite
         subjects affected / exposed
    3 / 7 (42.86%)
    31 / 77 (40.26%)
    12 / 24 (50.00%)
    10 / 38 (26.32%)
    3 / 41 (7.32%)
    6 / 50 (12.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 9 (44.44%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    8 / 40 (20.00%)
         occurrences all number
    3
    33
    14
    10
    4
    6
    0
    0
    5
    0
    0
    0
    13
    Hypophosphataemia
         subjects affected / exposed
    3 / 7 (42.86%)
    19 / 77 (24.68%)
    6 / 24 (25.00%)
    5 / 38 (13.16%)
    6 / 41 (14.63%)
    5 / 50 (10.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    1 / 9 (11.11%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    11 / 40 (27.50%)
         occurrences all number
    5
    29
    10
    5
    7
    7
    0
    1
    3
    3
    0
    0
    12
    Hyponatraemia
         subjects affected / exposed
    4 / 7 (57.14%)
    20 / 77 (25.97%)
    10 / 24 (41.67%)
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    3 / 9 (33.33%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    6 / 40 (15.00%)
         occurrences all number
    4
    26
    11
    3
    3
    1
    0
    1
    4
    4
    0
    0
    8
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 7 (28.57%)
    22 / 77 (28.57%)
    9 / 24 (37.50%)
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 9 (33.33%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    2
    24
    16
    4
    2
    0
    0
    0
    7
    2
    0
    0
    2
    Hypocalcaemia
         subjects affected / exposed
    2 / 7 (28.57%)
    23 / 77 (29.87%)
    11 / 24 (45.83%)
    4 / 38 (10.53%)
    1 / 41 (2.44%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    2
    25
    11
    4
    1
    2
    0
    0
    0
    0
    0
    0
    2
    Hypernatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 77 (0.00%)
    1 / 24 (4.17%)
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    2
    2
    0
    0
    0
    0
    1
    0
    0
    0
    3
    Hyperglycaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    12 / 77 (15.58%)
    6 / 24 (25.00%)
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 9 (33.33%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    4 / 40 (10.00%)
         occurrences all number
    0
    23
    26
    3
    2
    0
    0
    0
    9
    2
    0
    0
    6
    Hypomagnesaemia
         subjects affected / exposed
    2 / 7 (28.57%)
    5 / 77 (6.49%)
    4 / 24 (16.67%)
    6 / 38 (15.79%)
    2 / 41 (4.88%)
    5 / 50 (10.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    4 / 40 (10.00%)
         occurrences all number
    3
    5
    4
    7
    3
    9
    1
    0
    0
    0
    0
    0
    6
    Dehydration
         subjects affected / exposed
    2 / 7 (28.57%)
    5 / 77 (6.49%)
    4 / 24 (16.67%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    1 / 1 (100.00%)
    2 / 9 (22.22%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    2
    6
    4
    0
    0
    0
    0
    1
    5
    0
    0
    0
    2
    Hyperkalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    6 / 77 (7.79%)
    1 / 24 (4.17%)
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 50 (2.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    10
    3
    1
    0
    1
    0
    0
    1
    0
    0
    0
    1
    Hypermagnesaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 77 (1.30%)
    2 / 24 (8.33%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 9 (11.11%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    Malnutrition
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 77 (5.19%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Metabolic acidosis
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 77 (3.90%)
    0 / 24 (0.00%)
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 50 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    0 / 9 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    1
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Jan 2015
    • Visit windows for screening, leukapheresis, and Month 1 imaging were expanded to provide greater logistical flexibility for the subjects and study sites. • Additional toxicity assessments prior to the infusion of axicabtagene ciloleucel were added. • Recovery criteria for discharge of subject from hospital after Day 7 were expanded. • Grade 3 or higher CRS was designated for expedited safety reporting.
    27 Feb 2015
    • Total sample size of the study was increased from approximately 118–124 to 118– 136 subjects based upon the contingency for additional cohort assessment in Phase 1. • Exclusion criterion was added for subjects with a history of aminoglycoside hypersensitivity. • Cyclophosphamide dose for the initial A1 cohort in Phase 1 was increased from 300 to 500 mg/m2/day. • Contingency for an additional cohort (B1) added in the event that a more intensive lymphodepletion therapy is deemed warranted. Subjects would receive 30 mg/kg cyclophosphamide Days –7 and -6 and 25 mg/m2 fludarabine Days –5 through –1. • Objective response rate, the primary endpoint of Phase 2, was specified to be based on investigator assessment; response rate according to the central reviewer was designated as a secondary endpoint.
    27 Oct 2015
    • Enrollment was aligned with the day of leukapheresis. • Eligibility criteria governing renal, hepatic, cardiac, pulmonary function were revised (adding oxygen saturation of > 92%, adding cardiac and pleural effusion criteria). • Deep vein thrombosis and pulmonary embolism were added as exclusion criteria. • Clarification that indwelling line or drain were exclusion criteria but Ommaya reservoir and dedicated central venous access catheters were permitted. • Clarifications were made for the concomitant use of corticosteroids and other agents with immunosuppressive potential for the management of CRS and neurologic events. • Expanded instructions were given for management of possible hypotension and renal insufficiency arising from CRS; specifically, use of IV saline was detailed. • Blood samples were added for measurement of cytokine levels, CRP, and antibodies to axicabtagene ciloleucel or bovine serum albumin. • Expanded instructions were given about subject requirements prior to initiating leukapheresis; namely, no significant infection before proceeding with leukapheresis. • Instructions were added for subjects eligible to receive a second treatment with axicabtagene ciloleucel.
    18 Apr 2016
    • IND and EudraCT numbers added to title page. • Several eligibility criteria in Section 5 were clarified as related to prior radiation or systemic therapy, history of hepatitis B or C, history of CNS lymphoma, and history of autoimmune disease. • Section 6 was updated with additional toxicity management guidance to include specific treatments for CRS, management of cardiac toxicity, management of neurologic events, deep vein thrombosis prophylaxis. • Description of histiocytosis haematophagic/hemophagocytic lymphohistiocytosis (HLH) was added. • Lumbar puncture when expect expansion, infiltration of the CAR T cells, and neurologic events were added. • Confirmation of eligibility with PET-CT. • Recommendation that CRP, ferritin, and LDH (if elevated at baseline) be monitored daily starting at Day 0 through hospitalization.
    05 Jan 2022
    • A Long-term Follow-up (LTFU) protocol, KT-US-982-5968 has been developed to allow for rollover of subjects to complete the 15-year follow-up after infusion of KTE-C19 on the KTE-C19-101/ZUMA-1 study. Subjects will be provided the opportunity to rollover to the LTFU protocol after a minimum of 24-months follow-up for safety follow-up and reduced burden of study-specific assessments.
    22 Jun 2022
    • References to availability of retreatment with axicabtagene ciloleucel in the KT-US-982-5968 long-term follow-up (LTFU) have been removed following a separate amendment to the LTFU protocol.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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