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    Clinical Trial Results:
    A Phase 1 Dose Escalation, Open-Label Study of Venetoclax in Combination with Navitoclax and Chemotherapy in Subjects with Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma

    Summary
    EudraCT number
    		 2017-001541-26
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    14 Nov 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Jun 2021
    First version publication date
    20 Jun 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    M16-106
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03181126
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AbbVie
    Sponsor organisation address
    1 North Waukegan Road, North Chicago, IL, United States, 60064
    Public contact
    Global Medical Services, AbbVie, 001 800-633-9110, abbvieclinicaltrials@abbvie.com
    Scientific contact
    Global Medical Services, AbbVie, 001 800-633-9110, abbvieclinicaltrials@abbvie.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Nov 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Nov 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of the study were: - Evaluate the safety of venetoclax in combination with navitoclax; - Evaluate the safety of venetoclax in combination with navitoclax and chemotherapy; - Determine dose-limiting toxicities (DLTs) of venetoclax, navitoclax, and chemotherapy; - Assess the pharmacokinetics (PK) of venetoclax in combination with navitoclax.
    Protection of trial subjects
    Subject and/or legal guardian read and understood the information provided about the study and gave written permission.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Nov 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 11
    Country: Number of subjects enrolled
    United States: 58
    Worldwide total number of subjects
    69
    EEA total number of subjects
    0
    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)
    12
    Adolescents (12-17 years)
    6
    Adults (18-64 years)
    45
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was an open-label, Phase 1 dose escalation study in pediatric and adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) or R/R lymphoblastic lymphoma (LL). The study was conducted at 14 sites in the United States and Australia.

    Pre-assignment
    Screening details
    		 Dose escalation decisions were guided by Bayesian optimal interval design, which utilized a decision rule within each weight group (< 45 kg and ≥ 45 kg) based on cumulative numbers of patients who experienced a dose-limiting toxicity (DLT).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Venetoclax + Navitoclax 25 mg
    Arm description
    		 Participants ≥ 45 kg received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 and onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 25 mg administered daily. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    ABT-199 (GDC-0199)
    Other name
    VENCLEXTA®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered orally once a day at a dose adjusted by weight to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 onwards.

    Investigational medicinal product name
    Navitoclax
    Investigational medicinal product code
    ABT-263
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Navitoclax was administered orally once a day based on patient weight; dose level 1 was 25 mg for patients ≥ 45 kg only.

    Investigational medicinal product name
    Chemotherapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion, Tablet
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    The recommended chemotherapy schedule consisted of: - PEG-asparaginase 1250 IU/m^2 intravenous (IV) or intramuscular equivalent on days 1 and 15; - vincristine 1.5 mg/m^2 (maximum 2 mg) IV weekly on days 1, 8, 15, and 22; - dexamethasone 20 mg/m^2/day orally divided twice daily on days 1–5 and 15–19.

    Arm title
    		 Venetoclax + Navitoclax 50 mg
    Arm description
    		 Participants received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 50 mg (or 25 mg for subjects weighing < 45 kg) administered daily. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    ABT-199 (GDC-0199)
    Other name
    VENCLEXTA®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered orally once a day at a dose adjusted by weight to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg from Day 2 and thereafter.

    Investigational medicinal product name
    Navitoclax
    Investigational medicinal product code
    ABT-263
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Navitoclax was administered orally once a day based on patient weight; dose level 2 was 50 mg for ≥45 kg and 25 mg for 20 kg to <45 kg.

    Investigational medicinal product name
    Chemotherapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion, Tablet
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    The recommended chemotherapy schedule consisted of: - PEG-asparaginase 1250 IU/m^2 intravenous (IV) or intramuscular equivalent on days 1 and 15; - vincristine 1.5 mg/m^2 (maximum 2 mg) IV weekly on days 1, 8, 15, and 22; - dexamethasone 20 mg/m^2/day orally divided twice daily on days 1–5 and 15–19.

    Arm title
    		 Venetoclax + Navitoclax 100 mg
    Arm description
    		 Participants received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 100 mg (50 mg for subjects weighing < 45 kg) administered daily. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    ABT-199 (GDC-0199)
    Other name
    VENCLEXTA®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered orally once a day at a dose adjusted by weight to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg from Day 2 and thereafter.

    Investigational medicinal product name
    Navitoclax
    Investigational medicinal product code
    ABT-263
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Navitoclax was administered orally once a day based on patient weight; dose level 3 was 100 mg for ≥ 45 kg and 50 mg for 20 kg to < 45 kg.

    Investigational medicinal product name
    Chemotherapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion, Tablet
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    The recommended chemotherapy schedule consisted of: - PEG-asparaginase 1250 IU/m^2 intravenous (IV) or intramuscular equivalent on days 1 and 15; - vincristine 1.5 mg/m^2 (maximum 2 mg) IV weekly on days 1, 8, 15, and 22; - dexamethasone 20 mg/m^2/day orally divided twice daily on days 1–5 and 15–19.

    Arm title
    		 Safety Expansion
    Arm description
    		 Participants received oral venetoclax, adjusted by weight to match the exposure of the adult equivalent target dose of 400 mg daily and oral navitoclax 50 mg (25 mg for subjects weighing < 45 kg) administered daily for 21 days of every 28 days. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    ABT-199 (GDC-0199)
    Other name
    VENCLEXTA®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered orally once a day at a dose adjusted by weight to match the exposure of the adult equivalent target dose of 400 mg.

    Investigational medicinal product name
    Navitoclax
    Investigational medicinal product code
    ABT-263
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Navitoclax was administered orally at 50 mg daily for subjects weighing ≥ 45 kg or 25 mg daily for subjects weighing < 45 kg.

    Investigational medicinal product name
    Chemotherapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion, Tablet
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    The recommended chemotherapy schedule consisted of: - PEG-asparaginase 1250 IU/m^2 IV or intramuscular equivalent on days 1 and 15; - vincristine 1.5 mg/m^2 (maximum 2 mg) IV weekly on days 1, 8, 15, and 22; - dexamethasone 20 mg/m^2/day orally divided twice daily on days 1–5 and 15–19.

    Number of subjects in period 1
    		Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion
    Started
    16
    11
    20
    22
    Received venetoclax
    16
    11
    20
    22
    Received navitoclax
    16
    11
    19
    22
    Completed
    0
    0
    0
    0
    Not completed
    16
    11
    20
    22
         Consent withdrawn by subject
    -
    -
    -
    1
         Death
    13
    7
    14
    15
         Study terminated by sponsor
    3
    4
    5
    6
         Non-compliance
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Venetoclax + Navitoclax 25 mg
    Reporting group description
    		 Participants ≥ 45 kg received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 and onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 25 mg administered daily. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.

    Reporting group title
    Venetoclax + Navitoclax 50 mg
    Reporting group description
    		 Participants received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 50 mg (or 25 mg for subjects weighing < 45 kg) administered daily. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.

    Reporting group title
    Venetoclax + Navitoclax 100 mg
    Reporting group description
    		 Participants received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 100 mg (50 mg for subjects weighing < 45 kg) administered daily. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.

    Reporting group title
    Safety Expansion
    Reporting group description
    		 Participants received oral venetoclax, adjusted by weight to match the exposure of the adult equivalent target dose of 400 mg daily and oral navitoclax 50 mg (25 mg for subjects weighing < 45 kg) administered daily for 21 days of every 28 days. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.

    Reporting group values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion Total
    Number of subjects
    		 16 11 20 22 69
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        median (full range (min-max))
    		 30 (14 to 45) 20 (6 to 72) 28 (6 to 72) 28 (6 to 72) -
    Gender categorical
    Units: Subjects
        Female
    		 4 4 10 7 25
        Male
    		 12 7 10 15 44
    Race
    Units: Subjects
        White
    		 11 9 16 17 53
        Black or African American
    		 2 1 0 1 4
        Asian
    		 1 0 2 3 6
        American Indian or Alaska Native
    		 0 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 1 0 0 1
        Missing
    		 2 0 2 1 5
    Type of Primary Cancer
    Units: Subjects
        Acute lymphoblastic leukemia
    		 16 9 19 19 63
        Lymphoblastic lymphoma
    		 0 2 1 3 6

    End points

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    End points reporting groups
    Reporting group title
    Venetoclax + Navitoclax 25 mg
    Reporting group description
    		 Participants ≥ 45 kg received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 and onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 25 mg administered daily. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.

    Reporting group title
    Venetoclax + Navitoclax 50 mg
    Reporting group description
    		 Participants received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 50 mg (or 25 mg for subjects weighing < 45 kg) administered daily. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.

    Reporting group title
    Venetoclax + Navitoclax 100 mg
    Reporting group description
    		 Participants received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 100 mg (50 mg for subjects weighing < 45 kg) administered daily. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.

    Reporting group title
    Safety Expansion
    Reporting group description
    		 Participants received oral venetoclax, adjusted by weight to match the exposure of the adult equivalent target dose of 400 mg daily and oral navitoclax 50 mg (25 mg for subjects weighing < 45 kg) administered daily for 21 days of every 28 days. Participants may have received chemotherapy from Day 1 for up to 2 cycles at the discretion of the Investigator.

    Subject analysis set title
    Total
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All enrolled participants who received venetoclax and navitoclax.

    Subject analysis set title
    Pediatric
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects aged < 18 years.

    Subject analysis set title
    Adult
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects aged ≥ 18 years

    Subject analysis set title
    B-ALL
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects with B-cell acute lymphoblastic leukemia.

    Subject analysis set title
    T-ALL
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects with T-cell acute lymphoblastic leukemia.

    Subject analysis set title
    LL
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects with lymphoblastic lymphoma.

    Primary: Number of Participants with Dose-limiting Toxicities (DLTs)

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    End point title
    		 Number of Participants with Dose-limiting Toxicities (DLTs) [1] [2]
    End point description
    Subjects must have received at least 75% of venetoclax and navitoclax doses during the first 28 days or have experienced a DLT to be deemed evaluable for DLTs. Any Grade 3 or higher non-hematologic adverse event (AE) that concurs with the administration of venetoclax, navitoclax, or chemotherapy was considered a dose limiting toxicity except: - AEs that the Investigator determined are clearly due to an identifiable cause such as disease progression, underlying illness, and concurrent illness; - AEs related to a chemotherapy agent only (no causality to venetoclax or navitoclax) which are common and expected as determined by the Investigator and are managed - Grade 3 nausea, vomiting or diarrhea that is adequately managed with supportive care; - Infection; - Fever; -Electrolyte or laboratory abnormalities that resolve to Grade ≤ 2 within 7 days, without evidence of end organ damage, including those related to tumor lysis syndrome (TLS); - Clinical tumor lysis syndrome
    End point type
    Primary
    End point timeframe
    First 28 days of treatment
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analyses were not conducted.
    [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: Subjects in the safety expansion cohort were not evaluated for DLTs.
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg
    Number of subjects analysed
    15 [3]
    10 [4]
    13 [5]
    Units: participants
    1
    2
    5
    Notes
    [3] - DLT evaluable
    [4] - DLT evaluable
    [5] - DLT evaluable
    No statistical analyses for this end point

    Primary: Maximum Observed Plasma Concentration (Cmax) of Venetoclax

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Venetoclax [6]
    End point description
    Plasma concentrations of venetoclax were determined using a validated liquid/liquid extraction followed by high performance liquid chromatography with tandem mass spectrometric detection. The lower limit of quantitation (LLOQ) and upper limit of quantitation (ULOQ) were established at 2.12 ng/mL and 2030 ng/mL, respectively.
    End point type
    Primary
    End point timeframe
    Days 1, 2, 3, 8, and 9
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analyses were not conducted.
    End point values
    		 Total
    Number of subjects analysed
    64
    Units: µg/mL
    geometric mean (geometric coefficient of variation)
        Day 1 (200 mg): N=47
    0.553 ± 61
        Day 2 (400 mg): N=47
    0.985 ± 64
        Day 3 (400 mg): N=29
    1.25 ± 60
        Day 8 (400 mg): N=64
    1.48 ± 80
        Day 9 (400 mg): N=28
    1.24 ± 69
    No statistical analyses for this end point

    Primary: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax

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    End point title
    		 Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax [7]
    End point description
    End point type
    Primary
    End point timeframe
    Days 1, 2, 3, 8, and 9
    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: Statistical analyses were not conducted.
    End point values
    		 Total
    Number of subjects analysed
    64
    Units: hours
    median (full range (min-max))
        Day 1 (200 mg): N=47
    6.0 (4.0 to 24.0)
        Day 2 (400 mg): N=47
    6.0 (4.0 to 24.0)
        Day 3 (400 mg): N=29
    8.0 (4.0 to 9.8)
        Day 8 (400 mg): N=64
    6.0 (2.3 to 24.0)
        Day 9 (400 mg): N=28
    6.0 (3.7 to 8.0)
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve from Time Zero to 8 Hours (AUC8) of Venetoclax

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    End point title
    		 Area Under the Plasma Concentration-time Curve from Time Zero to 8 Hours (AUC8) of Venetoclax [8]
    End point description
    End point type
    Primary
    End point timeframe
    Days 1, 2, 3, 8, and 9
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analyses were not conducted.
    End point values
    		 Total
    Number of subjects analysed
    64
    Units: µg*h/mL
    geometric mean (geometric coefficient of variation)
        Day 1 (200 mg): N=47
    2.27 ± 69
        Day 2 (400 mg): N=47
    4.51 ± 60
        Day 3 (400 mg): N=28
    6.24 ± 64
        Day 8 (400 mg): N=64
    8.07 ± 81
        Day 9 (400 mg): N=28
    6.47 ± 78
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours (AUC24) for Venetoclax

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    End point title
    		 Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours (AUC24) for Venetoclax [9]
    End point description
    End point type
    Primary
    End point timeframe
    Days 1, 2, and 8
    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: Statistical analyses were not conducted.
    End point values
    		 Total
    Number of subjects analysed
    64
    Units: µg*h/mL
    geometric mean (geometric coefficient of variation)
        Day 1 (200 mg): N=47
    7.14 ± 65
        Day 2 (400 mg): N=29
    15.1 ± 65
        Day 8 (400mg): N=64
    22.7 ± 84
    No statistical analyses for this end point

    Primary: Maximum Observed Plasma Concentration (Cmax) of Navitoclax

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Navitoclax [10] [11]
    End point description
    Plasma concentrations of navitoclax were determined using a validated liquid/liquid extraction followed by high performance liquid chromatography with tandem mass spectrometric detection. The LLOQ and ULOQ for navitoclax were established at 5.07 ng/mL and 5070 ng/mL, respectively.
    End point type
    Primary
    End point timeframe
    Days 3, 8, and 9
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analyses were not conducted.
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Safety Expansion subjects are included in the Navitoclax 50 mg group for PK results
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg
    Number of subjects analysed
    16
    8 [12]
    18
    Units: µg/mL
    geometric mean (geometric coefficient of variation)
        Day 3 (N = 14, 8, 6)
    0.192 ± 60
    0.650 ± 17
    0.973 ± 49
        Day 8 (N = 16, 31, 18)
    0.326 ± 63
    1.09 ± 76
    1.50 ± 69
        Day 9 (N = 16, 8, 4)
    0.307 ± 63
    0.818 ± 57
    1.18 ± 47
    Notes
    [12] - Day 8 also includes subjects in the Safety Expansion cohort who received 50 mg navitoclax (N=31)
    No statistical analyses for this end point

    Primary: Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax

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    End point title
    		 Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax [13] [14]
    End point description
    End point type
    Primary
    End point timeframe
    Days 3, 8, and 9
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analyses were not conducted.
    [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: Safety Expansion subjects are included in the Navitoclax 50 mg group for PK results
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg
    Number of subjects analysed
    16
    8 [15]
    18
    Units: hours
    median (full range (min-max))
        Day 3 (N = 14, 8, 6)
    6.0 (4.0 to 9.8)
    6.0 (4.0 to 8.0)
    7.0 (4.0 to 8.0)
        Day 8 (N = 16, 31, 18)
    7.3 (3.4 to 8.0)
    6.0 (1.8 to 8.0)
    6.0 (4.0 to 24.0)
        Day 9 (N = 16, 8, 4)
    6.3 (0 to 8.0)
    6.0 (4.0 to 8.0)
    7.0 (6.0 to 8.0)
    Notes
    [15] - Day 8 also includes subjects in the Safety Expansion cohort who received 50 mg navitoclax (N=31)
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve from Time Zero to 8 Hours (AUC8) of Navitoclax

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    End point title
    		 Area Under the Plasma Concentration-time Curve from Time Zero to 8 Hours (AUC8) of Navitoclax [16] [17]
    End point description
    End point type
    Primary
    End point timeframe
    Days 3, 8, and 9
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analyses were not conducted.
    [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: Safety Expansion subjects are included in the Navitoclax 50 mg group for PK results
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg
    Number of subjects analysed
    16
    8 [18]
    18
    Units: µg*h/mL
    geometric mean (geometric coefficient of variation)
        Day 3 (N = 11, 8, 6)
    0.991 ± 58
    2.65 ± 24
    3.65 ± 46
        Day 8 (N = 16, 31, 18)
    1.74 ± 54
    6.07 ± 81
    8.55 ± 66
        Day 9 (N = 14, 8, 4)
    1.79 ± 65
    4.31 ± 57
    5.86 ± 43
    Notes
    [18] - Day 8 also includes subjects in the Safety Expansion cohort who received 50 mg navitoclax (N=31)
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours (AUC24) for Navitoclax

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    End point title
    		 Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours (AUC24) for Navitoclax [19] [20]
    End point description
    End point type
    Primary
    End point timeframe
    Day 8
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analyses were not conducted.
    [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: Safety Expansion subjects are included in the Navitoclax 50 mg group for PK results
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg
    Number of subjects analysed
    16
    8 [21]
    18
    Units: µg*h/mL
        geometric mean (geometric coefficient of variation)
    5.16 ± 59
    16.4 ± 82
    22.5 ± 62
    Notes
    [21] - Day 8 also includes 22 subjects in the Safety Expansion cohort who received 50 mg navitoclax (N=30)
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR)

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    End point title
    		 Overall Response Rate (ORR)
    End point description
    Overall response rate was defined as the percentage of participants with a complete response (CR), complete remission/response with incomplete marrow recovery (CRi) or complete response without platelet recovery (CRp) for subjects with acute lymphoblastic leukemia (ALL) and CR or partial response (PR) for subjects with lymphoblastic lymphoma (LL).
    End point type
    Secondary
    End point timeframe
    Up to the end of the study; median time on study was 19.1 months.
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion Pediatric Adult B-ALL T-ALL LL
    Number of subjects analysed
    16
    11
    19
    22
    18
    51
    36
    27
    6
    Units: percentage of participants
        number (confidence interval 95%)
    81.3 (54.4 to 96.0)
    81.8 (48.2 to 97.7)
    47.4 (24.4 to 71.1)
    68.2 (45.1 to 86.1)
    72.2 (46.5 to 90.3)
    64.7 (50.1 to 77.6)
    77.8 (60.8 to 89.9)
    51.9 (31.9 to 71.3)
    66.7 (22.3 to 95.7)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Complete Response

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    End point title
    		 Percentage of Participants with a Complete Response
    End point description
    The overall CR rate including CR, CRi, and CRp.
    End point type
    Secondary
    End point timeframe
    Up to the end of the study; median time on study was 19.1. months.
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion Pediatric Adult B-ALL T-ALL LL
    Number of subjects analysed
    16
    11
    19
    22
    18
    51
    36
    27
    6
    Units: percentage of participants
        number (confidence interval 95%)
    75.0 (47.6 to 92.7)
    72.7 (39.0 to 94.0)
    42.1 (20.3 to 66.5)
    50.0 (28.2 to 71.8)
    55.6 (30.8 to 78.5)
    56.9 (42.2 to 70.7)
    61.1 (43.5 to 76.9)
    48.1 (28.7 to 68.1)
    66.7 (22.3 to 95.7)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    Duration of response is defined as the number of days from first response (CR, CRi, CRp, or PR) until progressive disease (PD) or death, whichever occurred first. Only "responders" (i.e., subjects who achieved a CR, CRi, CRp, or PR) were included in the analysis. Duration of response was analyzed using Kaplan-Meier (KM) methodology. Participants with no PD or death were censored at the date of their last disease assessment. "99999" indicates values that could not be estimated.
    End point type
    Secondary
    End point timeframe
    Median time on follow-up was 19.1 months
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion Pediatric Adult B-ALL T-ALL LL
    Number of subjects analysed
    13
    9
    9
    15
    13
    33
    28
    14
    4
    Units: months
        median (confidence interval 95%)
    9.5 (1.4 to 12.3)
    8.5 (0.7 to 99999)
    3.8 (0.8 to 99999)
    2.1 (0.7 to 6.5)
    3.5 (0.7 to 99999)
    4.2 (2.1 to 9.1)
    6.5 (1.4 to 9.5)
    2.6 (1.0 to 99999)
    2.1 (0.6 to 99999)
    No statistical analyses for this end point

    Secondary: Duration of Complete Response (DoCR)

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    End point title
    		 Duration of Complete Response (DoCR)
    End point description
    Duration of complete response is defined as the number of days from first complete response (CR, CRi, or CRp) until PD or death, whichever occurred first. Only "responders" (i.e., subjects who achieved a CR, CRi, or CRp) were included in the analysis. Duration of complete response was analyzed using KM methodology. Participants with no PD or death were censored at the date of their last disease assessment. "99999" indicates values that could not be estimated.
    End point type
    Secondary
    End point timeframe
    Median duration of follow-up was 19.1. months.
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion Pediatric Adult B-ALL T-ALL LL
    Number of subjects analysed
    12
    8
    8
    11
    10
    29
    22
    13
    4
    Units: months
        median (confidence interval 95%)
    4.2 (0.9 to 11.2)
    8.8 (2.6 to 99999)
    10.3 (0.8 to 99999)
    2.4 (0.3 to 99999)
    6.9 (3.5 to 99999)
    6.5 (1.9 to 9.1)
    7.4 (2.4 to 9.5)
    3.4 (0.8 to 99999)
    2.1 (0.3 to 99999)
    No statistical analyses for this end point

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    Overall survival (OS) is defined as the time from first dose until death. OS was analyzed using KM methodology. Participants who were still alive were censored at the date of last contact. "99999" indicates values that could not be estimated.
    End point type
    Secondary
    End point timeframe
    Median time on follow-up was 19.1 months.
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion Pediatric Adult B-ALL T-ALL LL
    Number of subjects analysed
    16
    11
    19
    22
    18
    51
    36
    27
    6
    Units: months
        median (confidence interval 95%)
    9.7 (2.7 to 15.7)
    10.3 (3.3 to 99999)
    4.3 (0.8 to 11.2)
    5.2 (2.9 to 8.3)
    11.4 (2.9 to 99999)
    6.6 (3.3 to 8.3)
    8.8 (4.0 to 11.4)
    5.2 (2.9 to 7.7)
    7.3 (2.0 to 99999)
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS)

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    End point title
    		 Progression-Free Survival (PFS)
    End point description
    Progression-free survival was defined as the time from first dose until PD or death, whichever occurred first. PFS was analyzed using KM methodology. Participants with no PD or death were censored at the date of their last disease assessment. "99999" indicates values that could not be estimated.
    End point type
    Secondary
    End point timeframe
    Median time on follow-up was 19.1 months.
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion Pediatric Adult B-ALL T-ALL LL
    Number of subjects analysed
    16
    11
    19
    22
    18
    51
    36
    27
    6
    Units: months
        median (confidence interval 95%)
    4.7 (1.8 to 11.7)
    8.8 (1.6 to 99999)
    1.9 (0.8 to 5.4)
    1.7 (1.0 to 3.3)
    1.7 (1.5 to 99999)
    3.0 (1.8 to 5.4)
    4.7 (1.7 to 8.8)
    1.9 (1.6 to 4.7)
    1.7 (1.5 to 99999)
    No statistical analyses for this end point

    Secondary: Number of Participants Who Proceeded to Stem Cell Transplantation (SCT) or Chimeric Antigen Receptor T-cell (CAR-T) Therapy

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    End point title
    		 Number of Participants Who Proceeded to Stem Cell Transplantation (SCT) or Chimeric Antigen Receptor T-cell (CAR-T) Therapy
    End point description
    End point type
    Secondary
    End point timeframe
    Up to the end of the study; median time on study was 19.1. months.
    End point values
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion Pediatric Adult B-ALL T-ALL LL
    Number of subjects analysed
    16
    11
    19
    22
    18
    51
    36
    27
    6
    Units: participants
        SCT
    2
    5
    1
    5
    5
    8
    7
    3
    3
        CAR-T therapy
    2
    1
    2
    0
    3
    2
    5
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug to 30 days after last dose; Median times on venetoclax and navitoclax were 45 days (range, 1-597) and 39 days (range, 5-595), respectively.
    Adverse event reporting additional description
    One adult subject enrolled in the Venetoclax + Navitoclax 100 mg group discontinued from the study after receiving 1 dose of venetoclax and never received any navitoclax is included in the "total" column, but not the Venetoclax + Navitoclax 100 mg dose cohort.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Venetoclax + Navitoclax 25 mg
    Reporting group description
    		 Participants ≥ 45 kg received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 and onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 25 mg administered daily. Participants received chemotherapy at the discretion of the Investigator.

    Reporting group title
    Venetoclax + Navitoclax 50 mg
    Reporting group description
    		 Participants received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 50 mg (or 25 mg for subjects weighing < 45 kg) administered daily. Participants received chemotherapy at the discretion of the Investigator.

    Reporting group title
    Venetoclax + Navitoclax 100 mg
    Reporting group description
    		 Participants received oral venetoclax daily, adjusted by weight, to match the exposure of the adult equivalent target doses of 200 mg on Day 1 and 400 mg on Day 2 onwards for up to 37 weeks. From Day 3 participants also received oral navitoclax 100 mg (50 mg for subjects weighing < 45 kg) administered daily. Participants received chemotherapy at the discretion of the Investigator.

    Reporting group title
    Safety Expansion
    Reporting group description
    		 Participants received oral venetoclax, adjusted by weight to match the exposure of the adult equivalent target dose of 400 mg daily and oral navitoclax 50 mg (25 mg for subjects weighing < 45 kg) administered daily for 21 days of every 28 days. Participants also received chemotherapy at the discretion of the Investigator.

    Reporting group title
    Total
    Reporting group description
    		 All participants who received venetoclax, navitoclax, and chemotherapy. Includes one subject who did not receive navitoclax.

    Serious adverse events
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion Total
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 16 (87.50%)
    7 / 11 (63.64%)
    14 / 19 (73.68%)
    16 / 22 (72.73%)
    52 / 69 (75.36%)
         number of deaths (all causes)
    13
    7
    14
    15
    49
         number of deaths resulting from adverse events
    4
    0
    5
    1
    10
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEATH
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    MULTIPLE ORGAN DYSFUNCTION SYNDROME
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    2 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 3
    0 / 1
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    HYPERSENSITIVITY
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOXIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY DISTRESS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CONFUSIONAL STATE
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    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
    Investigations
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    CARDIAC ARREST
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    CARDIAC TAMPONADE
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERICARDIAL EFFUSION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    LETHARGY
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEUROTOXICITY
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    PRESYNCOPE
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEIZURE
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SOMNOLENCE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SPINAL CORD COMPRESSION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    5 / 16 (31.25%)
    5 / 11 (45.45%)
    3 / 19 (15.79%)
    6 / 22 (27.27%)
    20 / 69 (28.99%)
         occurrences causally related to treatment / all
    1 / 6
    4 / 6
    3 / 4
    5 / 6
    13 / 23
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PANCYTOPENIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    TYMPANIC MEMBRANE PERFORATION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ANAL FISTULA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ASCITES
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL ISCHAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    NAUSEA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIC COLITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS ACUTE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RECTAL PERFORATION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UPPER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    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
    VOMITING
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLECYSTITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHRONIC HEPATITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DRUG-INDUCED LIVER INJURY
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HEPATIC PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    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
    HEPATIC STEATOSIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    MYALGIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    BACTERAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CATHETER BACTERAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    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
    CELLULITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ESCHERICHIA SEPSIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    KLEBSIELLA SEPSIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MASTOIDITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MYRINGITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIC SEPSIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    3 / 22 (13.64%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PARAINFLUENZAE VIRUS INFECTION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 3
    2 / 6
    3 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    PNEUMONIA PSEUDOMONAL
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PSEUDOMONAL SEPSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    3 / 16 (18.75%)
    1 / 11 (9.09%)
    3 / 19 (15.79%)
    3 / 22 (13.64%)
    10 / 69 (14.49%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    1 / 4
    2 / 3
    3 / 12
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 3
    SEPTIC SHOCK
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 2
    1 / 3
    2 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    SKIN INFECTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    STREPTOCOCCAL INFECTION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    2 / 22 (9.09%)
    5 / 69 (7.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 3
    1 / 2
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VARICELLA ZOSTER PNEUMONIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VASCULAR DEVICE INFECTION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    1 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VULVITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DEHYDRATION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIABETIC KETOACIDOSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERGLYCAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOKALAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MALNUTRITION
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    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
    METABOLIC ACIDOSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Venetoclax + Navitoclax 25 mg Venetoclax + Navitoclax 50 mg Venetoclax + Navitoclax 100 mg Safety Expansion Total
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 16 (100.00%)
    11 / 11 (100.00%)
    19 / 19 (100.00%)
    22 / 22 (100.00%)
    69 / 69 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    OSTEOCHONDROMA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    Vascular disorders
    BRACHIOCEPHALIC VEIN THROMBOSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    2
    0
    0
    1
    3
    FLUSHING
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 11 (18.18%)
    2 / 19 (10.53%)
    2 / 22 (9.09%)
    7 / 69 (10.14%)
         occurrences all number
    1
    2
    2
    2
    7
    HOT FLUSH
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    1
    2
    HYPERTENSION
         subjects affected / exposed
    3 / 16 (18.75%)
    2 / 11 (18.18%)
    3 / 19 (15.79%)
    5 / 22 (22.73%)
    13 / 69 (18.84%)
         occurrences all number
    4
    2
    4
    5
    15
    HYPOTENSION
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 11 (9.09%)
    3 / 19 (15.79%)
    3 / 22 (13.64%)
    9 / 69 (13.04%)
         occurrences all number
    2
    1
    3
    4
    10
    JUGULAR VEIN THROMBOSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    2
    0
    0
    0
    2
    SUBCLAVIAN VEIN THROMBOSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    THROMBOPHLEBITIS SUPERFICIAL
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    VENOUS THROMBOSIS LIMB
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    1
    1
    2
    CATHETER SITE PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    2
    1
    3
    CHEST PAIN
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    CHILLS
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 11 (18.18%)
    2 / 19 (10.53%)
    4 / 22 (18.18%)
    8 / 69 (11.59%)
         occurrences all number
    0
    3
    2
    4
    9
    FACE OEDEMA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    1
    1
    2
    FACIAL PAIN
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    FATIGUE
         subjects affected / exposed
    2 / 16 (12.50%)
    5 / 11 (45.45%)
    6 / 19 (31.58%)
    11 / 22 (50.00%)
    25 / 69 (36.23%)
         occurrences all number
    2
    5
    7
    13
    28
    FEELING HOT
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    GAIT DISTURBANCE
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    1
    2
    3
    GENERALISED OEDEMA
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    6
    0
    0
    0
    6
    INJECTION SITE BRUISING
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    1
    2
    MALAISE
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    MEDICAL DEVICE PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
    3 / 69 (4.35%)
         occurrences all number
    0
    1
    0
    2
    3
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    4 / 16 (25.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    5 / 69 (7.25%)
         occurrences all number
    4
    1
    0
    0
    5
    OEDEMA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    2
    1
    3
    OEDEMA PERIPHERAL
         subjects affected / exposed
    2 / 16 (12.50%)
    3 / 11 (27.27%)
    6 / 19 (31.58%)
    6 / 22 (27.27%)
    18 / 69 (26.09%)
         occurrences all number
    2
    3
    6
    10
    22
    PAIN
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences all number
    3
    0
    1
    3
    7
    PERIPHERAL SWELLING
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    1
    1
    1
    0
    3
    PYREXIA
         subjects affected / exposed
    4 / 16 (25.00%)
    2 / 11 (18.18%)
    5 / 19 (26.32%)
    2 / 22 (9.09%)
    13 / 69 (18.84%)
         occurrences all number
    6
    2
    6
    2
    16
    SWELLING
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    SWELLING FACE
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    2
    0
    0
    0
    2
    UNEVALUABLE EVENT
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    3 / 22 (13.64%)
    4 / 69 (5.80%)
         occurrences all number
    1
    0
    0
    3
    4
    WITHDRAWAL SYNDROME
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    Reproductive system and breast disorders
    ERECTILE DYSFUNCTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    GENITAL PAIN
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    OEDEMA GENITAL
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    2
    0
    2
    PENILE PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    SCROTAL OEDEMA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    VAGINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    ASPIRATION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    ATELECTASIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    COUGH
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 11 (18.18%)
    1 / 19 (5.26%)
    5 / 22 (22.73%)
    9 / 69 (13.04%)
         occurrences all number
    1
    2
    1
    5
    9
    DRY THROAT
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    DYSPNOEA
         subjects affected / exposed
    3 / 16 (18.75%)
    1 / 11 (9.09%)
    2 / 19 (10.53%)
    1 / 22 (4.55%)
    7 / 69 (10.14%)
         occurrences all number
    3
    1
    2
    1
    7
    EPISTAXIS
         subjects affected / exposed
    6 / 16 (37.50%)
    2 / 11 (18.18%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    9 / 69 (13.04%)
         occurrences all number
    6
    2
    0
    1
    9
    HICCUPS
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    4 / 69 (5.80%)
         occurrences all number
    2
    0
    1
    1
    4
    HYPOXIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    1
    0
    1
    1
    3
    INCREASED UPPER AIRWAY SECRETION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    LUNG INFILTRATION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    MEDIASTINAL MASS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    NASAL CONGESTION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 11 (9.09%)
    3 / 19 (15.79%)
    1 / 22 (4.55%)
    7 / 69 (10.14%)
         occurrences all number
    2
    1
    4
    1
    8
    PLEURAL EFFUSION
         subjects affected / exposed
    4 / 16 (25.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    1 / 22 (4.55%)
    7 / 69 (10.14%)
         occurrences all number
    4
    0
    2
    1
    7
    PLEURITIC PAIN
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    1
    2
    PNEUMOMEDIASTINUM
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    PRODUCTIVE COUGH
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    1 / 22 (4.55%)
    5 / 69 (7.25%)
         occurrences all number
    2
    0
    3
    1
    6
    PULMONARY EMBOLISM
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    PULMONARY MASS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    PULMONARY OEDEMA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    4 / 19 (21.05%)
    0 / 22 (0.00%)
    5 / 69 (7.25%)
         occurrences all number
    1
    0
    4
    0
    5
    RESPIRATORY DISTRESS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    RESPIRATORY FAILURE
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    4 / 69 (5.80%)
         occurrences all number
    3
    0
    1
    0
    4
    RESPIRATORY TRACT HAEMORRHAGE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    RHINORRHOEA
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
    4 / 69 (5.80%)
         occurrences all number
    1
    1
    0
    3
    5
    SINUS CONGESTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    TACHYPNOEA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    1
    2
    WHEEZING
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    3 / 19 (15.79%)
    0 / 22 (0.00%)
    4 / 69 (5.80%)
         occurrences all number
    1
    0
    3
    0
    4
    Psychiatric disorders
    ADJUSTMENT DISORDER
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    AFFECT LABILITY
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    AGITATION
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    0
    1
    2
    ANXIETY
         subjects affected / exposed
    4 / 16 (25.00%)
    2 / 11 (18.18%)
    2 / 19 (10.53%)
    1 / 22 (4.55%)
    9 / 69 (13.04%)
         occurrences all number
    4
    2
    2
    1
    9
    CONFUSIONAL STATE
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences all number
    3
    0
    1
    3
    7
    DELIRIUM
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    2
    1
    0
    1
    4
    DEPRESSED MOOD
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    DEPRESSION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    1
    0
    1
    1
    3
    DYSPHORIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    HALLUCINATION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    INSOMNIA
         subjects affected / exposed
    7 / 16 (43.75%)
    2 / 11 (18.18%)
    3 / 19 (15.79%)
    6 / 22 (27.27%)
    18 / 69 (26.09%)
         occurrences all number
    7
    2
    5
    6
    20
    MENTAL STATUS CHANGES
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    2 / 22 (9.09%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    2
    2
    4
    RESTLESSNESS
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    Investigations
    ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    2 / 19 (10.53%)
    6 / 22 (27.27%)
    10 / 69 (14.49%)
         occurrences all number
    3
    1
    3
    7
    14
    AEROMONAS TEST POSITIVE
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    6 / 16 (37.50%)
    4 / 11 (36.36%)
    4 / 19 (21.05%)
    8 / 22 (36.36%)
    22 / 69 (31.88%)
         occurrences all number
    12
    6
    6
    13
    37
    AMMONIA INCREASED
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    AMYLASE INCREASED
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    2 / 22 (9.09%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    2
    2
    4
    ANTITHROMBIN III DECREASED
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    4 / 16 (25.00%)
    1 / 11 (9.09%)
    4 / 19 (21.05%)
    9 / 22 (40.91%)
    18 / 69 (26.09%)
         occurrences all number
    8
    1
    5
    14
    28
    BACTERIAL TEST POSITIVE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    4 / 22 (18.18%)
    9 / 69 (13.04%)
         occurrences all number
    4
    0
    4
    7
    15
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    2 / 16 (12.50%)
    3 / 11 (27.27%)
    5 / 19 (26.32%)
    8 / 22 (36.36%)
    18 / 69 (26.09%)
         occurrences all number
    2
    4
    10
    13
    29
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    3 / 22 (13.64%)
    7 / 69 (10.14%)
         occurrences all number
    2
    0
    3
    4
    9
    BLOOD FIBRINOGEN DECREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences all number
    3
    1
    2
    3
    9
    BLOOD LACTIC ACID INCREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    BLOOD PHOSPHORUS INCREASED
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    BLOOD UREA INCREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    BLOOD URIC ACID INCREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    ELECTROCARDIOGRAM QT PROLONGED
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    2
    0
    0
    1
    3
    ELECTROCARDIOGRAM T WAVE ABNORMAL
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    2
    0
    0
    3
    INTERNATIONAL NORMALISED RATIO INCREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    1
    2
    LIPASE INCREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    3 / 22 (13.64%)
    5 / 69 (7.25%)
         occurrences all number
    1
    0
    1
    4
    6
    LIVER FUNCTION TEST INCREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    2
    0
    0
    0
    2
    LYMPHOCYTE COUNT DECREASED
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    2 / 19 (10.53%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences all number
    0
    4
    4
    5
    13
    LYMPHOCYTE COUNT INCREASED
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    4
    0
    4
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    5 / 22 (22.73%)
    8 / 69 (11.59%)
         occurrences all number
    2
    3
    3
    6
    14
    PLATELET COUNT DECREASED
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    4 / 19 (21.05%)
    4 / 22 (18.18%)
    9 / 69 (13.04%)
         occurrences all number
    0
    3
    9
    7
    19
    PROTHROMBIN TIME PROLONGED
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    TRANSAMINASES INCREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    URINARY SEDIMENT PRESENT
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    VITAMIN D DECREASED
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    WEIGHT DECREASED
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    4 / 22 (18.18%)
    8 / 69 (11.59%)
         occurrences all number
    5
    0
    2
    4
    11
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    2 / 19 (10.53%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences all number
    0
    1
    4
    3
    8
    Injury, poisoning and procedural complications
    AGITATION POSTOPERATIVE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    CONTUSION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    2 / 22 (9.09%)
    5 / 69 (7.25%)
         occurrences all number
    1
    0
    2
    3
    6
    FALL
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    2 / 22 (9.09%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    2
    2
    4
    INFUSION RELATED REACTION
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    4 / 69 (5.80%)
         occurrences all number
    2
    0
    1
    1
    4
    PROCEDURAL PAIN
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    1
    0
    0
    2
    TRANSFUSION REACTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    VASCULAR ACCESS COMPLICATION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    Congenital, familial and genetic disorders
    ANTITHROMBIN III DEFICIENCY
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences all number
    1
    1
    1
    3
    6
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    BRADYCARDIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    2
    2
    LEFT VENTRICULAR DYSFUNCTION
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    1
    0
    2
    SINUS TACHYCARDIA
         subjects affected / exposed
    4 / 16 (25.00%)
    2 / 11 (18.18%)
    4 / 19 (21.05%)
    1 / 22 (4.55%)
    11 / 69 (15.94%)
         occurrences all number
    4
    2
    5
    1
    12
    SUPRAVENTRICULAR TACHYCARDIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    TACHYCARDIA
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 11 (9.09%)
    3 / 19 (15.79%)
    7 / 22 (31.82%)
    13 / 69 (18.84%)
         occurrences all number
    2
    1
    3
    8
    14
    VENTRICULAR EXTRASYSTOLES
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    2
    1
    3
    Nervous system disorders
    ALTERED STATE OF CONSCIOUSNESS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    BALANCE DISORDER
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    BURNING SENSATION
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    CLUMSINESS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    DISTURBANCE IN ATTENTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    DIZZINESS
         subjects affected / exposed
    4 / 16 (25.00%)
    2 / 11 (18.18%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    8 / 69 (11.59%)
         occurrences all number
    4
    3
    1
    1
    9
    DYSGEUSIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    2
    0
    2
    EPIDURAL LIPOMATOSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    HEADACHE
         subjects affected / exposed
    4 / 16 (25.00%)
    3 / 11 (27.27%)
    4 / 19 (21.05%)
    5 / 22 (22.73%)
    16 / 69 (23.19%)
         occurrences all number
    4
    5
    5
    5
    19
    HEMIPARESIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    HYPERSOMNIA
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    HYPOAESTHESIA
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 11 (18.18%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    2
    0
    0
    2
    LETHARGY
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    MEMORY IMPAIRMENT
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    MENTAL IMPAIRMENT
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    MYOCLONUS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    2
    0
    2
    0
    4
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    4 / 16 (25.00%)
    2 / 11 (18.18%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
    8 / 69 (11.59%)
         occurrences all number
    5
    2
    0
    2
    9
    PARAESTHESIA
         subjects affected / exposed
    2 / 16 (12.50%)
    4 / 11 (36.36%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    7 / 69 (10.14%)
         occurrences all number
    2
    4
    1
    0
    7
    PERIPHERAL MOTOR NEUROPATHY
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    2 / 22 (9.09%)
    5 / 69 (7.25%)
         occurrences all number
    1
    0
    3
    2
    6
    SCIATICA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    SEIZURE
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    SOMNOLENCE
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    1
    0
    2
    TREMOR
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    0
    2
    0
    1
    3
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    4 / 16 (25.00%)
    3 / 11 (27.27%)
    6 / 19 (31.58%)
    10 / 22 (45.45%)
    23 / 69 (33.33%)
         occurrences all number
    7
    6
    11
    11
    35
    BONE MARROW FAILURE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    2
    0
    0
    0
    2
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    3 / 16 (18.75%)
    2 / 11 (18.18%)
    4 / 19 (21.05%)
    2 / 22 (9.09%)
    11 / 69 (15.94%)
         occurrences all number
    3
    2
    5
    2
    12
    HYPOFIBRINOGENAEMIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    INCREASED TENDENCY TO BRUISE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    2
    0
    0
    0
    2
    LEUKOPENIA
         subjects affected / exposed
    3 / 16 (18.75%)
    2 / 11 (18.18%)
    3 / 19 (15.79%)
    4 / 22 (18.18%)
    12 / 69 (17.39%)
         occurrences all number
    11
    6
    8
    4
    29
    LYMPHADENOPATHY
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    NEUTROPENIA
         subjects affected / exposed
    6 / 16 (37.50%)
    4 / 11 (36.36%)
    4 / 19 (21.05%)
    6 / 22 (27.27%)
    20 / 69 (28.99%)
         occurrences all number
    11
    9
    7
    8
    35
    PANCYTOPENIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    1
    2
    SPLENOMEGALY
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    THROMBOCYTOPENIA
         subjects affected / exposed
    4 / 16 (25.00%)
    2 / 11 (18.18%)
    3 / 19 (15.79%)
    5 / 22 (22.73%)
    14 / 69 (20.29%)
         occurrences all number
    5
    5
    5
    6
    21
    Ear and labyrinth disorders
    HYPOACUSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    Eye disorders
    DRY EYE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    EYE PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    EYE PRURITUS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    OCULAR DISCOMFORT
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    OCULAR HYPERAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    2
    2
    VISION BLURRED
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    4 / 69 (5.80%)
         occurrences all number
    2
    1
    0
    1
    4
    Gastrointestinal disorders
    ABDOMINAL DISTENSION
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences all number
    2
    0
    1
    3
    6
    ABDOMINAL PAIN
         subjects affected / exposed
    5 / 16 (31.25%)
    4 / 11 (36.36%)
    9 / 19 (47.37%)
    7 / 22 (31.82%)
    26 / 69 (37.68%)
         occurrences all number
    6
    4
    11
    8
    30
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    0 / 22 (0.00%)
    5 / 69 (7.25%)
         occurrences all number
    3
    0
    2
    0
    5
    ABDOMINAL TENDERNESS
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    2
    0
    0
    0
    2
    ANAL INCONTINENCE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    ANORECTAL DISCOMFORT
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    ASCITES
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    COLITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    2 / 19 (10.53%)
    2 / 22 (9.09%)
    5 / 69 (7.25%)
         occurrences all number
    0
    1
    2
    2
    5
    CONSTIPATION
         subjects affected / exposed
    4 / 16 (25.00%)
    2 / 11 (18.18%)
    2 / 19 (10.53%)
    9 / 22 (40.91%)
    17 / 69 (24.64%)
         occurrences all number
    4
    2
    2
    9
    17
    DENTAL CARIES
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    DIARRHOEA
         subjects affected / exposed
    9 / 16 (56.25%)
    5 / 11 (45.45%)
    7 / 19 (36.84%)
    13 / 22 (59.09%)
    35 / 69 (50.72%)
         occurrences all number
    14
    10
    8
    15
    48
    DISCOLOURED VOMIT
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    DRY MOUTH
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    1
    0
    0
    2
    DYSCHEZIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    DYSPEPSIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    1 / 22 (4.55%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    2
    1
    4
    DYSPHAGIA
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    4 / 69 (5.80%)
         occurrences all number
    3
    0
    1
    0
    4
    ENTEROCOLITIS HAEMORRHAGIC
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    FLATULENCE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    GASTRITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    2
    0
    2
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 11 (9.09%)
    2 / 19 (10.53%)
    3 / 22 (13.64%)
    8 / 69 (11.59%)
         occurrences all number
    2
    2
    2
    3
    9
    GINGIVAL BLEEDING
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    GINGIVAL PAIN
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    GLOSSODYNIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    HAEMATOCHEZIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    0 / 22 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    1
    0
    2
    0
    3
    HAEMORRHOIDS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    HYPERAESTHESIA TEETH
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    HYPOAESTHESIA ORAL
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    ILEUS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    INTRA-ABDOMINAL FLUID COLLECTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    LIP SWELLING
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    LOWER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    MELAENA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    MOUTH HAEMORRHAGE
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    2
    0
    0
    0
    2
    NAUSEA
         subjects affected / exposed
    10 / 16 (62.50%)
    5 / 11 (45.45%)
    6 / 19 (31.58%)
    14 / 22 (63.64%)
    36 / 69 (52.17%)
         occurrences all number
    13
    6
    9
    17
    46
    NEUTROPENIC COLITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    OESOPHAGEAL PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    OESOPHAGEAL ULCER
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    ORAL DISORDER
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    ORAL MUCOSAL BLISTERING
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    ORAL MUCOSAL EXFOLIATION
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    ORAL PAIN
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    PARAESTHESIA ORAL
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    PROCTALGIA
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    1
    0
    2
    PROCTITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    1
    0
    1
    1
    3
    RETCHING
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    STOMATITIS
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    2
    0
    0
    0
    3
    TOOTH LOSS
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    TOOTHACHE
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    2 / 22 (9.09%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    1
    2
    3
    VOMITING
         subjects affected / exposed
    6 / 16 (37.50%)
    4 / 11 (36.36%)
    7 / 19 (36.84%)
    9 / 22 (40.91%)
    26 / 69 (37.68%)
         occurrences all number
    9
    5
    11
    10
    35
    Hepatobiliary disorders
    HEPATIC LESION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    HEPATIC STEATOSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
    3 / 69 (4.35%)
         occurrences all number
    1
    0
    0
    2
    3
    HEPATITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    HYPERBILIRUBINAEMIA
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences all number
    5
    0
    0
    4
    9
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    1
    0
    0
    2
    DECUBITUS ULCER
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    DERMATITIS ACNEIFORM
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    3 / 22 (13.64%)
    6 / 69 (8.70%)
         occurrences all number
    2
    0
    1
    3
    6
    DRY SKIN
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    ECCHYMOSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    ERYTHEMA
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    1
    0
    0
    2
    ERYTHEMA MULTIFORME
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    HIDRADENITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    HYPERHIDROSIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    INGROWING NAIL
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    NIGHT SWEATS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    1
    0
    1
    1
    3
    PETECHIAE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    PRURITUS
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    4 / 69 (5.80%)
         occurrences all number
    1
    1
    1
    1
    4
    PURPURA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    RASH MACULAR
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    RASH MACULO-PAPULAR
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    2 / 19 (10.53%)
    1 / 22 (4.55%)
    4 / 69 (5.80%)
         occurrences all number
    0
    1
    2
    1
    4
    RASH PAPULAR
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    SKIN HYPERPIGMENTATION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    SKIN IRRITATION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    SKIN LESION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    SKIN MASS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    3
    0
    0
    2
    5
    DYSURIA
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    1
    1
    2
    0
    4
    HAEMATURIA
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
    5 / 69 (7.25%)
         occurrences all number
    2
    1
    0
    2
    5
    RENAL FAILURE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    RENAL TUBULAR NECROSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    URINARY INCONTINENCE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    URINARY RETENTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    Endocrine disorders
    ADRENAL INSUFFICIENCY
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    CUSHINGOID
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    HYPERTHYROIDISM
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    5 / 16 (31.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    2 / 22 (9.09%)
    8 / 69 (11.59%)
         occurrences all number
    7
    0
    1
    3
    11
    ARTHRITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    BACK PAIN
         subjects affected / exposed
    5 / 16 (31.25%)
    3 / 11 (27.27%)
    3 / 19 (15.79%)
    3 / 22 (13.64%)
    14 / 69 (20.29%)
         occurrences all number
    5
    3
    3
    4
    15
    BONE PAIN
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 11 (9.09%)
    3 / 19 (15.79%)
    0 / 22 (0.00%)
    6 / 69 (8.70%)
         occurrences all number
    2
    1
    3
    0
    6
    FLANK PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    3 / 22 (13.64%)
    4 / 69 (5.80%)
         occurrences all number
    0
    0
    1
    3
    4
    GROIN PAIN
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    LUMBAR SPINAL STENOSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    MUSCLE SPASMS
         subjects affected / exposed
    4 / 16 (25.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
    6 / 69 (8.70%)
         occurrences all number
    5
    0
    0
    2
    7
    MUSCULAR WEAKNESS
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 11 (9.09%)
    3 / 19 (15.79%)
    3 / 22 (13.64%)
    9 / 69 (13.04%)
         occurrences all number
    2
    1
    4
    3
    10
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    4 / 22 (18.18%)
    5 / 69 (7.25%)
         occurrences all number
    0
    0
    1
    4
    5
    MYALGIA
         subjects affected / exposed
    4 / 16 (25.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    5 / 69 (7.25%)
         occurrences all number
    4
    0
    1
    0
    5
    MYOPATHY
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    NECK PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    PAIN IN EXTREMITY
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    4 / 19 (21.05%)
    3 / 22 (13.64%)
    9 / 69 (13.04%)
         occurrences all number
    2
    0
    4
    3
    9
    SPINAL PAIN
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    1
    1
    2
    Infections and infestations
    ADENOVIRUS INFECTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    BACTERAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    CANDIDA INFECTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    0 / 22 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    1
    0
    2
    0
    3
    CELLULITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    4 / 69 (5.80%)
         occurrences all number
    2
    1
    0
    1
    4
    CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    2
    0
    1
    0
    3
    CYTOMEGALOVIRUS INFECTION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    CYTOMEGALOVIRUS VIRAEMIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    ESCHERICHIA BACTERAEMIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    INCISION SITE CELLULITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    INFECTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    MENINGITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    MUCOSAL INFECTION
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    NASOPHARYNGITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    ORAL CANDIDIASIS
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    OROPHARYNGEAL CANDIDIASIS
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    1
    0
    0
    1
    PARONYCHIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    PNEUMONIA
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 11 (18.18%)
    2 / 19 (10.53%)
    1 / 22 (4.55%)
    7 / 69 (10.14%)
         occurrences all number
    2
    2
    2
    1
    7
    PNEUMONIA ADENOVIRAL
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    PNEUMONIA FUNGAL
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    RASH PUSTULAR
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    RESPIRATORY SYNCYTIAL VIRUS INFECTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    RHINITIS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    RHINOVIRUS INFECTION
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    3 / 69 (4.35%)
         occurrences all number
    3
    0
    0
    0
    3
    SEPSIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    1
    2
    SINUSITIS
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    1
    2
    SKIN INFECTION
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    SOFT TISSUE INFECTION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    STREPTOCOCCAL BACTERAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    0
    1
    1
    0
    2
    STREPTOCOCCAL INFECTION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    SUBCUTANEOUS ABSCESS
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 11 (18.18%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    5 / 69 (7.25%)
         occurrences all number
    1
    2
    1
    1
    5
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    3 / 69 (4.35%)
         occurrences all number
    0
    1
    1
    1
    3
    Metabolism and nutrition disorders
    APPETITE DISORDER
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    DECREASED APPETITE
         subjects affected / exposed
    3 / 16 (18.75%)
    1 / 11 (9.09%)
    6 / 19 (31.58%)
    6 / 22 (27.27%)
    16 / 69 (23.19%)
         occurrences all number
    3
    1
    8
    7
    19
    DEHYDRATION
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    2 / 22 (9.09%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    1
    2
    3
    ELECTROLYTE IMBALANCE
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    2
    0
    0
    0
    2
    FLUID OVERLOAD
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    4 / 69 (5.80%)
         occurrences all number
    1
    1
    1
    1
    4
    GOUT
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    1
    0
    0
    0
    1
    HYPERAMMONAEMIA
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    1
    0
    0
    2
    HYPERCALCAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    4
    4
    HYPERGLYCAEMIA
         subjects affected / exposed
    4 / 16 (25.00%)
    2 / 11 (18.18%)
    4 / 19 (21.05%)
    8 / 22 (36.36%)
    18 / 69 (26.09%)
         occurrences all number
    8
    2
    9
    13
    32
    HYPERKALAEMIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    4 / 19 (21.05%)
    2 / 22 (9.09%)
    7 / 69 (10.14%)
         occurrences all number
    1
    0
    4
    3
    8
    HYPERMAGNESAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    2 / 22 (9.09%)
    3 / 69 (4.35%)
         occurrences all number
    0
    0
    2
    3
    5
    HYPERNATRAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    3
    1
    4
    HYPERPHOSPHATAEMIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    2 / 22 (9.09%)
    5 / 69 (7.25%)
         occurrences all number
    1
    0
    2
    2
    5
    HYPERTRIGLYCERIDAEMIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    4 / 22 (18.18%)
    6 / 69 (8.70%)
         occurrences all number
    2
    0
    1
    6
    9
    HYPERURICAEMIA
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    2 / 22 (9.09%)
    2 / 69 (2.90%)
         occurrences all number
    0
    0
    0
    3
    3
    HYPOALBUMINAEMIA
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 11 (18.18%)
    4 / 19 (21.05%)
    8 / 22 (36.36%)
    16 / 69 (23.19%)
         occurrences all number
    4
    3
    6
    13
    26
    HYPOCALCAEMIA
         subjects affected / exposed
    4 / 16 (25.00%)
    1 / 11 (9.09%)
    7 / 19 (36.84%)
    7 / 22 (31.82%)
    19 / 69 (27.54%)
         occurrences all number
    10
    1
    12
    9
    32
    HYPOGLYCAEMIA
         subjects affected / exposed
    1 / 16 (6.25%)
    3 / 11 (27.27%)
    4 / 19 (21.05%)
    3 / 22 (13.64%)
    11 / 69 (15.94%)
         occurrences all number
    1
    5
    6
    4
    16
    HYPOKALAEMIA
         subjects affected / exposed
    7 / 16 (43.75%)
    5 / 11 (45.45%)
    11 / 19 (57.89%)
    14 / 22 (63.64%)
    37 / 69 (53.62%)
         occurrences all number
    17
    8
    17
    17
    59
    HYPOMAGNESAEMIA
         subjects affected / exposed
    4 / 16 (25.00%)
    2 / 11 (18.18%)
    4 / 19 (21.05%)
    11 / 22 (50.00%)
    21 / 69 (30.43%)
         occurrences all number
    4
    2
    9
    14
    29
    HYPONATRAEMIA
         subjects affected / exposed
    6 / 16 (37.50%)
    2 / 11 (18.18%)
    4 / 19 (21.05%)
    8 / 22 (36.36%)
    20 / 69 (28.99%)
         occurrences all number
    8
    3
    7
    13
    31
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 11 (18.18%)
    4 / 19 (21.05%)
    9 / 22 (40.91%)
    16 / 69 (23.19%)
         occurrences all number
    3
    3
    7
    11
    24
    HYPOVOLAEMIA
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2
    INCREASED APPETITE
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    1 / 69 (1.45%)
         occurrences all number
    0
    0
    1
    0
    1
    INSULIN RESISTANCE
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 22 (4.55%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    0
    1
    2
    TUMOUR LYSIS SYNDROME
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 22 (0.00%)
    2 / 69 (2.90%)
         occurrences all number
    1
    0
    1
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Mar 2018
    LL patient population added to the study, clarification that both relapsed and refractory populations of both ALL and LL were eligible for the study, updated the age range and added LL and ALL with Ph+ populations to the inclusion criteria, clarified exclusion criteria, updated meal and dietary requirements, added guidelines for outpatient monitoring of TLS, updates to list of excluded and cautionary medications.
    29 Mar 2018
    Updated TKI doses and differentiate pediatric doses from adult doses in Table 6, Added IM as alternative route of administration of pegasparaginase.
    08 Oct 2018
    Included secondary objective of number of subjects who proceed to CAR-T therapy, update to Study Design to change first day of chemotherapy administration to Day 1, updated exclusion criteria, updated requirements for lumbar puncture and radiographic scans, updated toxicity management.
    23 Oct 2018
    Updated protocol language to align with current venetoclax Standard Safety Risk Language.
    12 Mar 2019
    Added option of alternative steroids, added exception to Inclusion Criterion 3, updated throughout the protocol to indicate that subjects on venetoclax may enroll and remain on venetoclax, clarified toxicity management to indicate that venetoclax or navitoclax could be held at any time to allow for count recovery per investigator discretion.
    29 Aug 2019
    Pathology report added, allowed for lower doses of dexamethasone, updated and clarified inclusion and exclusion criteria, differentiated toxicity management guidelines for dose escalation subjects, clarified language regarding subjects who continued dosing beyond Week 37, reduced PK sample schedule for safety expansion cohort, added safety expansion cohort with intermittent dosing.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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