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    Clinical Trial Results:
    A Phase 1 Dose Escalation and Phase 2 Randomized Double-Blind Study of Veliparib in Combination with Carboplatin and Etoposide as a Therapy of Treatment-Naïve Extensive Stage Disease Small Cell Lung Cancer

    Summary
    EudraCT number
    		 2014-001764-35
    Trial protocol
    		 ES   NL   CZ   BE   HU   FR  
    Global end of trial date
    17 Apr 2019

    Results information
    Results version number
    		 v2(current)
    This version publication date
    22 May 2020
    First version publication date
    30 Apr 2020
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Need to correct a table in the safety section of the report.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    M14-361
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02289690
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Abbvie Deutschland GmbH & Co.KG
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Maidenhead, Berkshire, United Kingdom, SL6-4UB
    Public contact
    Global Medical Services, AbbVie, 011 800-633-9110,
    Scientific contact
    Bruce Bach, MD, AbbVie, bruce.bach@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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    17 Apr 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Apr 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of the Phase 1 dose-escalation were: - To establish the maximum tolerated dose (MTD) and to establish the recommended Phase 2 dose (RPTD) and schedule for veliparib in combination with carboplatin and etoposide. - To evaluate the pharmacokinetic (PK) interaction between veliparib and etoposide. The primary objective of Phase 2 was: - To evaluate if veliparib in combination with carboplatin and etoposide followed by veliparib maintenance monotherapy results in improved progression-free survival vs. placebo in combination with carboplatin and etoposide followed by placebo monotherapy in subjects with treatment-naïve extensive stage small-cell lung cancer (ED SCLC).
    Protection of trial subjects
    All subjects entering the study had to sign an informed consent that was explained to them and questions encouraged.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Oct 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 24
    Country: Number of subjects enrolled
    United States: 44
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Belgium: 12
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Czech Republic: 6
    Country: Number of subjects enrolled
    France: 10
    Country: Number of subjects enrolled
    Hungary: 24
    Country: Number of subjects enrolled
    Korea, Republic of: 17
    Country: Number of subjects enrolled
    Netherlands: 36
    Country: Number of subjects enrolled
    Romania: 1
    Country: Number of subjects enrolled
    Russian Federation: 41
    Worldwide total number of subjects
    221
    EEA total number of subjects
    113
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    131
    From 65 to 84 years
    88
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 52 study sites located in 12 countries (Australia, Belgium, Canada, Czech Republic, France, Hungary, Korea, the Netherlands, Romania, Russian Federation, Spain, United States).

    Pre-assignment
    Screening details
    		 Participants in Phase 1 were sequentially assigned to ascending dose levels of veliparib in combination with standard carboplatin/etoposide regimen. Participants in Phase 2 were randomized equally to placebo, carboplatin/etoposide followed by placebo maintenance, or to veliparib, carboplatin/etoposide followed by veliparib or placebo maintenance.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Subject
    Blinding implementation details
    Phase 1 was open-label. Participants in Phase 2 were randomized using an Interactive Response Technology (IRT) system. All study site personnel, including the investigator, study coordinator, as well as the subjects, remained blinded to the treatment throughout the course of the Phase 2 portion of the study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide
    Arm description
    		 Participants received 80 mg veliparib orally twice a day (BID) on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered intravenously (IV) on Day 1 at a target area under the curve (AUC) 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    ABT-888
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules administered orally twice a day according to the dosing schedule.

    Arm title
    		 Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide
    Arm description
    		 Participants received 120 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    ABT-888
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules administered orally twice a day according to the dosing schedule.

    Arm title
    		 Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide
    Arm description
    		 Participants received 160 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    ABT-888
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules administered orally twice a day according to the dosing schedule.

    Arm title
    		 Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide
    Arm description
    		 Participants received 200 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    ABT-888
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules administered orally twice a day according to the dosing schedule.

    Arm title
    		 Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide
    Arm description
    		 Participants received 240 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    ABT-888
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules administered orally twice a day according to the dosing schedule.

    Arm title
    		 Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide
    Arm description
    		 Participants received 240 mg veliparib orally BID on Days -2 to 12 (14 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 12 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    ABT-888
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules administered orally twice a day according to the dosing schedule.

    Arm title
    		 Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide
    Arm description
    		 Participants received 240 mg veliparib orally BID on Days -2 to Day 19 (continuous schedule) in combination with carboplatin/etoposide for up to four 21-day cycles. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    ABT-888
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules administered orally twice a day according to the dosing schedule.

    Arm title
    		 Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib
    Arm description
    		 Participants in Arm A received veliparib 240 mg BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min administered on Day 1, and etoposide 100 mg/m² administered on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    ABT-888
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Veliparib capsules administered orally twice a day according to the dosing schedule.

    Arm title
    		 Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo
    Arm description
    		 Participants In Arm B received veliparib 240 mg BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min administered on Day 1, and etoposide 100 mg/m² administered on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression received placebo monotherapy BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    ABT-888
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Veliparib capsules administered orally twice a day according to the dosing schedule.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo capsules administered orally twice a day according to the dosing schedule.

    Arm title
    		 Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Arm description
    		 Participants in Arm C received placebo BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min on Day 1, and etoposide 100 mg/m² on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression received placebo monotherapy BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo capsules administered orally twice a day according to the dosing schedule.

    Number of subjects in period 1
    		Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Started
    4
    3
    4
    3
    8
    14
    4
    61
    59
    61
    Received Study Drug
    4
    3
    4
    3
    8
    14
    4
    60
    58
    60
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    4
    3
    4
    3
    8
    14
    4
    61
    59
    61
         Adverse Event Related to Progression
    -
    1
    1
    -
    1
    -
    1
    -
    -
    -
         Consent withdrawn by subject
    1
    -
    -
    -
    1
    1
    -
    -
    4
    2
         Other
    -
    -
    -
    1
    1
    -
    1
    2
    3
    1
         Death
    -
    -
    -
    -
    -
    -
    -
    49
    45
    41
         Sponsor Discontinued Study
    -
    -
    -
    -
    -
    -
    -
    9
    7
    15
         Progressive Disease, Per Protocol
    3
    2
    3
    2
    5
    13
    2
    -
    -
    -
         Lost to follow-up
    -
    -
    -
    -
    -
    -
    -
    1
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 80 mg veliparib orally twice a day (BID) on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered intravenously (IV) on Day 1 at a target area under the curve (AUC) 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 120 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 160 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 200 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 240 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 240 mg veliparib orally BID on Days -2 to 12 (14 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 12 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 240 mg veliparib orally BID on Days -2 to Day 19 (continuous schedule) in combination with carboplatin/etoposide for up to four 21-day cycles. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib
    Reporting group description
    		 Participants in Arm A received veliparib 240 mg BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min administered on Day 1, and etoposide 100 mg/m² administered on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo
    Reporting group description
    		 Participants In Arm B received veliparib 240 mg BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min administered on Day 1, and etoposide 100 mg/m² administered on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression received placebo monotherapy BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Reporting group description
    		 Participants in Arm C received placebo BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min on Day 1, and etoposide 100 mg/m² on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression received placebo monotherapy BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group values
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo Phase 2: Placebo + Carboplatin/Etoposide -> Placebo Total
    Number of subjects
    		 4 3 4 3 8 14 4 61 59 61 221
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        median (full range (min-max))
    		 74.0 (55.0 to 79.0) 69.0 (62.0 to 75.0) 62.5 (56.0 to 74.0) 54.0 (52.0 to 68.0) 52.0 (43.0 to 63.0) 66.0 (52.0 to 72.0) 59.0 (57.0 to 62.0) 62.0 (39.0 to 77.0) 64.0 (46.0 to 86.0) 63.0 (37.0 to 87.0) -
    Gender categorical
    Units: Subjects
        Female
    		 3 0 2 1 2 5 1 21 21 23 79
        Male
    		 1 3 2 2 6 9 3 40 38 38 142
    Race
    Units: Subjects
        White
    		 4 3 4 3 8 14 4 55 51 52 198
        Black or African American
    		 0 0 0 0 0 0 0 2 1 1 4
        Asian
    		 0 0 0 0 0 0 0 4 7 7 18
        Missing
    		 0 0 0 0 0 0 0 0 0 1 1
    Eastern Cooperative Oncology Group (ECOG) Performance Status
    Measure Description: ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)
    Units: Subjects
        0 - Fully active
    		 1 1 1 1 2 3 2 21 16 23 71
        1 - Restricted but ambulatory
    		 3 2 3 2 5 11 1 39 42 37 145
        Missing
    		 0 0 0 0 1 0 1 1 1 1 5

    End points

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    End points reporting groups
    Reporting group title
    Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 80 mg veliparib orally twice a day (BID) on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered intravenously (IV) on Day 1 at a target area under the curve (AUC) 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 120 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 160 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 200 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 240 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 240 mg veliparib orally BID on Days -2 to 12 (14 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 12 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 240 mg veliparib orally BID on Days -2 to Day 19 (continuous schedule) in combination with carboplatin/etoposide for up to four 21-day cycles. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib
    Reporting group description
    		 Participants in Arm A received veliparib 240 mg BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min administered on Day 1, and etoposide 100 mg/m² administered on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo
    Reporting group description
    		 Participants In Arm B received veliparib 240 mg BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min administered on Day 1, and etoposide 100 mg/m² administered on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression received placebo monotherapy BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Reporting group description
    		 Participants in Arm C received placebo BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min on Day 1, and etoposide 100 mg/m² on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression received placebo monotherapy BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Subject analysis set title
    Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide Combined
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received 240 mg veliparib orally BID (Days -2 to 5 for 7-day schedule, Days -2 to 12 for 14-day schedule or Days -2 to 19 for continuous dosing) in combination with carboplatin/etoposide for up to four 21-day cycles. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle.

    Subject analysis set title
    Etoposide Cycle 1 Day 1 (With Veliparib)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Phase 1 participants received 100 mg/m² etoposide intravenously with carboplatin target AUC 5.0 mg*min/mL and veliparib 80 to 240 mg BID on Cycle 1 Day 1.

    Subject analysis set title
    Etoposide Cycle 2 Day 1 (No Veliparib)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Phase 1 participants received etoposide 100 mg/m² and carboplatin target AUC 5.0 mg*min/mL on Day 1 of Cycle 2. No veliparib was administered.

    Primary: Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)

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    End point title
    		 Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) [1] [2]
    End point description
    A DLT was defined as any of the following drug-related toxicities, graded according to the Common Toxicity Criteria for Adverse Events (CTCAE), V.4.0: 1. Events associated with treatment delay >14 days in initiating Cycle 2 therapy: Grade 4 thrombocytopenia, neutropenia, or febrile neutropenia, or Grade 3 febrile neutropenia with fever for > 7 days 2. Grade ≥ 3 non-hematologic toxicity with ≥ 2 grade increase from baseline and attributed to veliparib treatment, excluding nausea or vomiting for ≤ 48 hours or inadequately treated, electrolyte abnormalities resolving in ≤ 24 hours, hypersensitivity reactions or alopecia 3. Grade 2 non-hematologic toxicity of ≥ 2 grade increase from baseline, attributed to veliparib treatment requiring delay of >14 days in initiation of Cycle 2 4. Any toxicity of ≥ 2-grade increase from baseline, attributed to veliparib and requiring a dose modification in Cycle 1 or omission of carboplatin, >1 daily etoposide dose, or >30% veliparib doses in Cycle 1
    End point type
    Primary
    End point timeframe
    Cycle 1 Day –2 to pre-dose on Cycle 2 Day 1 (23 days)
    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: Safety results were analyzed descriptively.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 1 only.
    End point values
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide
    Number of subjects analysed
    4
    3
    4
    3
    8
    14
    4
    Units: participants
    0
    0
    0
    0
    1
    0
    1
    No statistical analyses for this end point

    Primary: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Veliparib

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    End point title
    		 Phase 1: Maximum Observed Plasma Concentration (Cmax) of Veliparib [3] [4]
    End point description
    Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL. The number of participants analyzed includes participants who were administered at least 1 dose of study drug, had at least 1 reported PK sample concentration and for whom Cmax could be calculated.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Pharmacokinetics were analyzed descriptively.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 1 only.
    End point values
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide Combined
    Number of subjects analysed
    4
    3
    4
    3
    22
    Units: μg/mL
        geometric mean (geometric coefficient of variation)
    0.620 ± 17
    1.00 ± 31
    1.39 ± 29
    1.44 ± 10
    1.99 ± 25
    No statistical analyses for this end point

    Primary: Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Veliparib

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    End point title
    		 Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Veliparib [5] [6]
    End point description
    Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL. The number of participants analyzed includes participants who were administered at least 1 dose of study drug, had at least 1 reported PK sample concentration and for whom Tmax could be calculated.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Pharmacokinetics were analyzed descriptively.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 1 only.
    End point values
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide Combined
    Number of subjects analysed
    4
    3
    4
    3
    22
    Units: hours
        median (full range (min-max))
    2.0 (1.0 to 2.0)
    1.0 (1.0 to 2.0)
    1.5 (1.0 to 2.0)
    2.0 (1.0 to 2.0)
    1.0 (1.0 to 3.0)
    No statistical analyses for this end point

    Primary: Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose (AUC[0-8]) of Veliparib

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    End point title
    		 Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose (AUC[0-8]) of Veliparib [7] [8]
    End point description
    The area under the plasma concentration-time curve from time 0 to 8 hours post-dose for veliparib was estimated using non-compartmental methods. The number of participants analyzed includes participants who were administered at least 1 dose of study drug, had at least 1 reported PK sample concentration and for whom AUC(0-8) could be calculated.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
    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: Pharmacokinetics were analyzed descriptively.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 1 only.
    End point values
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide Combined
    Number of subjects analysed
    4
    3
    4
    2
    22
    Units: μg*h/mL
        geometric mean (geometric coefficient of variation)
    3.18 ± 14
    4.24 ± 25
    7.51 ± 28
    6.66 ± 4
    9.29 ± 37
    No statistical analyses for this end point

    Primary: Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC[0-12]) of Veliparib

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    End point title
    		 Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC[0-12]) of Veliparib [9] [10]
    End point description
    The area under the plasma concentration-time curve from time 0 to 12 hours post-dose for veliparib was estimated using non-compartmental methods. AUC(0-12) was calculated by assuming the concentration at 12 hours post-dose was the same as the pre-dose concentration. The number of participants analyzed includes participants who were administered at least 1 dose of study drug, had at least 1 reported PK sample concentration and for whom AUC(0-12) could be calculated.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
    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: Pharmacokinetics were analyzed descriptively.
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 1 only.
    End point values
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide Combined
    Number of subjects analysed
    4
    3
    4
    3
    22
    Units: μg*h/mL
        geometric mean (geometric coefficient of variation)
    4.07 ± 15
    5.25 ± 27
    9.71 ± 31
    8.35 ± 6
    11.6 ± 40
    No statistical analyses for this end point

    Primary: Phase 1: Dose-normalized Maximum Observed Plasma Concentration of Veliparib

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    End point title
    		 Phase 1: Dose-normalized Maximum Observed Plasma Concentration of Veliparib [11] [12]
    End point description
    Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL. Dose normalized Cmax is calculated as Cmax / veliparib dose in mg. The number of participants analyzed includes participants who were administered at least 1 dose of study drug, had at least 1 reported PK sample concentration and for whom Cmax could be calculated.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Pharmacokinetics were analyzed descriptively.
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 1 only.
    End point values
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide Combined
    Number of subjects analysed
    4
    3
    4
    3
    22
    Units: (ng/mL)/mg
        geometric mean (geometric coefficient of variation)
    7.75 ± 16
    8.35 ± 31
    8.66 ± 29
    7.19 ± 10
    8.31 ± 25
    No statistical analyses for this end point

    Primary: Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose of Veliparib

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    End point title
    		 Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose of Veliparib [13] [14]
    End point description
    The area under the plasma concentration-time curve from time 0 to 8 hours post-dose for veliparib was estimated using non-compartmental methods. Dose normalized AUC(0-8) is calculated as AUC(0-8) / veliparib dose in mg. The number of participants analyzed includes participants who were administered at least 1 dose of study drug, had at least 1 reported PK sample concentration and for whom AUC(0-8) could be calculated.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
    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: Pharmacokinetics were analyzed descriptively.
    [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: Endpoint pertains to Phase 1 only.
    End point values
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide Combined
    Number of subjects analysed
    4
    3
    4
    2
    22
    Units: (ng*h/mL)/mg
        geometric mean (geometric coefficient of variation)
    39.8 ± 14
    35.3 ± 25
    46.9 ± 28
    33.3 ± 4
    38.7 ± 37
    No statistical analyses for this end point

    Primary: Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose of Veliparib

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    End point title
    		 Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose of Veliparib [15] [16]
    End point description
    The area under the plasma concentration-time curve from time 0 to 12 hours post-dose for veliparib was estimated using non-compartmental methods. AUC(0-12) was calculated by assuming the concentration at 12 hours post-dose was the same as the pre-dose concentration. Dose normalized AUC(0-12) is calculated as AUC(0-12) / veliparib dose in mg. The number of participants analyzed includes participants who were administered at least 1 dose of study drug, had at least 1 reported PK sample concentration and for whom AUC(0-12) could be calculated.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose
    Notes
    [15] - 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: Pharmacokinetics were analyzed descriptively.
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 1 only.
    End point values
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide Combined
    Number of subjects analysed
    4
    3
    4
    3
    22
    Units: (ng*h/mL)/mg
        geometric mean (geometric coefficient of variation)
    50.9 ± 15
    43.8 ± 27
    60.7 ± 31
    41.7 ± 6
    48.5 ± 40
    No statistical analyses for this end point

    Primary: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib

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    End point title
    		 Phase 1: Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib [17]
    End point description
    Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. The number of participants analyzed includes participants who received at least 1 dose of study drug, had at least 1 reported PK sample concentration for each time point and for whom Cmax could be calculated. Participants in the Veliparib 240 mg BID 21-day (continuous) dosing group and participants whose etoposide dose was reduced in Cycle 2 are not included in the Cycle 2 Day 1 analysis.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
    Notes
    [17] - 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: Pharmacokinetics were analyzed descriptively.
    End point values
    		 Etoposide Cycle 1 Day 1 (With Veliparib) Etoposide Cycle 2 Day 1 (No Veliparib)
    Number of subjects analysed
    37
    23
    Units: μg/mL
        geometric mean (geometric coefficient of variation)
    16.9 ± 18
    16.4 ± 21
    No statistical analyses for this end point

    Primary: Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Etoposide With and Without Veliparib

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    End point title
    		 Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Etoposide With and Without Veliparib [18]
    End point description
    Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. The number of participants analyzed includes participants who received at least 1 dose of study drug, had at least 1 reported PK sample concentration for each time point and for whom Tmax could be calculated. Participants in the Veliparib 240 mg BID 21-day (continuous) dosing group are not included in the Cycle 2 Day 1 analysis.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
    Notes
    [18] - 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: Pharmacokinetics were analyzed descriptively.
    End point values
    		 Etoposide Cycle 1 Day 1 (With Veliparib) Etoposide Cycle 2 Day 1 (No Veliparib)
    Number of subjects analysed
    37
    28
    Units: hours
        median (full range (min-max))
    0.9 (0.8 to 3.0)
    0.9 (0.9 to 3.7)
    No statistical analyses for this end point

    Primary: Phase 1: Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib

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    End point title
    		 Phase 1: Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib [19]
    End point description
    The area under the plasma concentration-time curve from 0 to the last measurable concentration (24 hours) of etoposide was estimated using using non-compartmental methods. The number of participants analyzed includes participants who received at least 1 dose of study drug, had at least 1 reported PK sample concentration for each time point and for whom AUC(0-t) could be calculated. Participants in the Veliparib 240 mg BID 21-day (continuous) dosing group and participants whose etoposide dose was reduced in Cycle 2 are not included in the Cycle 2 Day 1 analysis.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
    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: Pharmacokinetics were analyzed descriptively.
    End point values
    		 Etoposide Cycle 1 Day 1 (With Veliparib) Etoposide Cycle 2 Day 1 (No Veliparib)
    Number of subjects analysed
    35
    22
    Units: μg*h/mL
        geometric mean (geometric coefficient of variation)
    102 ± 23
    94.7 ± 18
    No statistical analyses for this end point

    Primary: Phase 1: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib

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    End point title
    		 Phase 1: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib [20]
    End point description
    The area under the plasma concentration-time curve from 0 to infinity for etoposide was estimated using using non-compartmental methods. The number of participants analyzed includes participants who received at least 1 dose of study drug, had at least 1 reported PK sample concentration for each time point and for whom AUC(0-∞) could be calculated. Participants in the Veliparib 240 mg BID 21-day (continuous) dosing group and participants whose etoposide dose was reduced in Cycle 2 are not included in the Cycle 2 Day 1 analysis.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
    Notes
    [20] - 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: Pharmacokinetics were analyzed descriptively.
    End point values
    		 Etoposide Cycle 1 Day 1 (With Veliparib) Etoposide Cycle 2 Day 1 (No Veliparib)
    Number of subjects analysed
    35
    22
    Units: μg*h/m
        geometric mean (geometric coefficient of variation)
    112 ± 56
    99.5 ± 18
    No statistical analyses for this end point

    Primary: Phase 1: Terminal Phase Elimination Half-life (t1/2) of Etoposide With and Without Veliparib

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    End point title
    		 Phase 1: Terminal Phase Elimination Half-life (t1/2) of Etoposide With and Without Veliparib [21]
    End point description
    The terminal half-life of etoposide was estimated using using non-compartmental methods. Values reported represent the harmonic mean ± pseudo-standard deviation. The number of participants analyzed includes participants who received at least 1 dose of study drug, had at least 1 reported PK sample concentration for each time point and for whom t1/2 could be calculated. Participants in the Veliparib 240 mg BID 21-day (continuous) dosing group are not included in the Cycle 2 Day 1 analysis.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
    Notes
    [21] - 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: Pharmacokinetics were analyzed descriptively.
    End point values
    		 Etoposide Cycle 1 Day 1 (With Veliparib) Etoposide Cycle 2 Day 1 (No Veliparib)
    Number of subjects analysed
    35
    27
    Units: hours
        arithmetic mean (standard deviation)
    5.7 ± 1.5
    5.0 ± 1.2
    No statistical analyses for this end point

    Primary: Phase 1: Dose-normalized Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib

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    End point title
    		 Phase 1: Dose-normalized Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib [22]
    End point description
    Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. Dose normalized Cmax is calculated as Cmax / etoposide dose in mg/m². The number of participants analyzed includes participants who received at least 1 dose of study drug, had at least 1 reported PK sample concentration for each time point and for whom Cmax could be calculated. Participants in the Veliparib 240 mg BID 21-day (continuous) dosing group are not included in the Cycle 2 Day 1 analysis.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
    Notes
    [22] - 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: Pharmacokinetics were analyzed descriptively.
    End point values
    		 Etoposide Cycle 1 Day 1 (With Veliparib) Etoposide Cycle 2 Day 1 (No Veliparib)
    Number of subjects analysed
    37
    28
    Units: (ng/mL)/(mg/m²)
        geometric mean (geometric coefficient of variation)
    169 ± 18
    170 ± 20
    No statistical analyses for this end point

    Primary: Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib

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    End point title
    		 Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib [23]
    End point description
    The area under the plasma concentration-time curve from 0 to the last measurable concentration (24 hours) of etoposide was estimated using using non-compartmental methods. Dose normalized AUC(0-t) is calculated as AUC(0-t) / etoposide dose in mg/m². The number of participants analyzed includes participants who received at least 1 dose of study drug, had at least 1 reported PK sample concentration for each time point and for whom AUC(0-t) could be calculated. Participants in the Veliparib 240 mg BID 21-day (continuous) dosing group are not included in the Cycle 2 Day 1 analysis.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
    Notes
    [23] - 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: Pharmacokinetics were analyzed descriptively.
    End point values
    		 Etoposide Cycle 1 Day 1 (With Veliparib) Etoposide Cycle 2 Day 1 (No Veliparib)
    Number of subjects analysed
    35
    27
    Units: (ng*h/mL)/(mg/m²)
        geometric mean (geometric coefficient of variation)
    1020 ± 23
    952 ± 21
    No statistical analyses for this end point

    Primary: Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib

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    End point title
    		 Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib [24]
    End point description
    The area under the plasma concentration-time curve from 0 to infinity for etoposide was estimated using using non-compartmental methods. Dose normalized AUC(0-∞) is calculated as AUC(0-∞) / etoposide dose in mg/m². The number of participants analyzed includes participants who received at least 1 dose of study drug, had at least 1 reported PK sample concentration for each time point and for whom AUC(0-∞) could be calculated. Participants in the Veliparib 240 mg BID 21-day (continuous) dosing group are not included in the Cycle 2 Day 1 analysis.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.
    Notes
    [24] - 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: Pharmacokinetics were analyzed descriptively.
    End point values
    		 Etoposide Cycle 1 Day 1 (With Veliparib) Etoposide Cycle 2 Day 1 (No Veliparib)
    Number of subjects analysed
    35
    27
    Units: ng*h/mL)/(mg/m²)
        geometric mean (geometric coefficient of variation)
    1120 ± 56
    1020 ± 20
    No statistical analyses for this end point

    Primary: Phase 2: Progression-free Survival

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    End point title
    		 Phase 2: Progression-free Survival [25]
    End point description
    Progression-free survival (PFS) is defined as the time from the date of randomization to the date of earliest radiographic disease progression or death if no radiographic disease progression occurred. If a participant did not have an event of disease progression and had not died on or prior to the cutoff for PFS analysis, the participant was censored at the date of their last disease assessment or randomization date provided they did not have any post-baseline disease assessment. Disease assessments were performed using computed tomography according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Progressive Disease (PD) was defined as at least a 20% increase in the size of target lesions and an absolute increase of at least 5 mm taking as reference the smallest lesion size recorded since the treatment started (baseline or after), or the appearance of 1 or more new lesions. The number of participants analyzed includes all participants randomized in Phase 2.
    End point type
    Primary
    End point timeframe
    From randomization up to the date the 126th PFS event was reached; Median time on follow-up was 7.3, 7.1, and 8.9 months in each treatment group respectively.
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 2 only.
    End point values
    		 Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Number of subjects analysed
    61
    59
    61
    Units: months
        median (confidence interval 80%)
    5.8 (5.6 to 6.8)
    5.7 (5.6 to 5.8)
    5.6 (5.1 to 6.7)
    Statistical analysis title
    		 Primary Analysis of PFS (Arm A vs. Arm C)
    Statistical analysis description
    The primary efficacy analysis in the Phase 2 portion of the study was the comparison of PFS among participants who received veliparib in combination with carboplatin and etoposide followed by veliparib maintenance monotherapy (Arm A) vs. placebo in combination with carboplatin and etoposide followed by placebo maintenance monotherapy (Arm C). The hazard ratio was estimated from a Cox proportional hazards model stratified by lactate dehydrogenase (LDH) level. A hazard ratio < 1 favors Arm A.
    Comparison groups
    Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib v Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [26]
    P-value
    		 = 0.059 [27]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.665
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.503
         upper limit
    		 0.88
    Notes
    [26] - Statistical significance was determined by a two-sided p-value ≤ 0.2.
    [27] - Two-sided log-rank test stratified by lactate dehydrogenase (LDH) level.
    Statistical analysis title
    		 Secondary Analysis of PFS (Arm B vs. Arm C)
    Statistical analysis description
    The analysis of PFS between Arm B versus Arm C was considered a secondary endpoint in the testing hierarchy (see details below), and was compared using a two-sided log-rank test stratified by LDH level. The hazard ratio was estimated from a Cox proportional hazards model stratified by LDH level. A hazard ratio of < 1 favors Arm B.
    Comparison groups
    Phase 2: Placebo + Carboplatin/Etoposide -> Placebo v Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [28]
    P-value
    		 = 0.924 [29]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.979
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.744
         upper limit
    		 1.288
    Notes
    [28] - If the primary analysis of PFS (Arm A vs Arm C) was statistically significant a fixed sequence testing procedure was to be performed with a 2-sided significance level of 0.2 for the following key secondary endpoints: OS (Arm A vs Arm C) PFS (Arms B vs Arm C) OS (Arm B vs Arm C) ORR (Arm A vs Arm C) ORR (Arm B vs Arm C) If significance versus Arm C was not demonstrated, all endpoints later in the testing hierarchy were to be considered exploratory.
    [29] - Two-sided log-rank test stratified by lactate dehydrogenase (LDH) level.

    Secondary: Phase 2: Overall Survival

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    End point title
    		 Phase 2: Overall Survival [30]
    End point description
    Overall survival (OS) is defined as the time from the date of randomization to the date of death. If a participant did not die on or prior to the end of study, the participant was censored at the date of their last known alive date, which is defined as the last date of the last survival follow-up visit, the start date of the last adverse event (AE), the start date or end date of the last dose of any study drugs, the last lab and vital sign collection date, or the last disease assessment date, whichever occurred last. The number of participants analyzed includes all participants randomized in Phase 2.
    End point type
    Secondary
    End point timeframe
    From randomization until the end of study (after a total of 136 OS events); median time on follow-up was 10.0, 8.6, and 11.7 months in each treatment group respectively.
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 2 only.
    End point values
    		 Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Number of subjects analysed
    61
    59
    61
    Units: months
        median (confidence interval 80%)
    10.1 (9.2 to 11.4)
    10.0 (8.0 to 12.7)
    12.4 (11.1 to 13.6)
    Statistical analysis title
    		 Overall Survival of Arm A vs. Arm C
    Statistical analysis description
    The analysis of OS between Arm A versus Arm C was a key secondary endpoint in the testing hierarchy (see details below), and was compared using a two-sided log-rank test stratified by LDH level. The hazard ratio was estimated from a Cox proportional hazards model stratified by LDH level. A hazard ratio of < 1 favors Arm A.
    Comparison groups
    Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib v Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [31]
    P-value
    		 = 0.088 [32]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.432
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 1.092
         upper limit
    		 1.879
    Notes
    [31] - If the primary analysis of PFS (Arm A vs Arm C) was statistically significant a fixed sequence testing procedure was to be performed with a 2-sided significance level of 0.2 for the following key secondary endpoints: OS (Arm A vs Arm C) PFS (Arms B vs Arm C) OS (Arm B vs Arm C) ORR (Arm A vs Arm C) ORR (Arm B vs Arm C) If significance versus Arm C was not demonstrated, all endpoints later in the testing hierarchy were to be considered exploratory.
    [32] - Two-sided log rank test stratified by LDH level.
    Statistical analysis title
    		 Overall Survival of Arm B vs. Arm C
    Statistical analysis description
    The analysis of OS between Arm B versus Arm C was a key secondary endpoint in the testing hierarchy (see details below), and was compared using a two-sided log-rank test stratified by LDH level. The hazard ratio was estimated from a Cox proportional hazards model stratified by LDH level. A hazard ratio of < 1 favors Arm B.
    Comparison groups
    Phase 2: Placebo + Carboplatin/Etoposide -> Placebo v Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [33]
    P-value
    		 = 0.083 [34]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.46
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 1.104
         upper limit
    		 1.931
    Notes
    [33] - If the primary analysis of PFS (Arm A vs Arm C) was statistically significant a fixed sequence testing procedure was to be performed with a 2-sided significance level of 0.2 for the following key secondary endpoints: OS (Arm A vs Arm C) PFS (Arms B vs Arm C) OS (Arm B vs Arm C) ORR (Arm A vs Arm C) ORR (Arm B vs Arm C) If significance versus Arm C was not demonstrated, all endpoints later in the testing hierarchy were to be considered exploratory.
    [34] - Two-sided log rank test stratified by LDH level.

    Secondary: Phase 2: Objective Response Rate

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    End point title
    		 Phase 2: Objective Response Rate [35]
    End point description
    Objective response rate (ORR) is defined as the percentage of participants with objective response (confirmed) as assessed by the investigator using RECIST version 1.1. Objective response includes both complete response (CR) and partial response (PR). Response must be confirmed at a subsequent tumor assessment at least 28 days apart. Participants with no post-baseline confirmed response were counted as non-responders. CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. No new lesions. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and no new lesions. The number of participants analyzed includes all participants randomized in Phase 2.
    End point type
    Secondary
    End point timeframe
    Tumor assessments were performed every 6 weeks for the first 30 weeks and every 9 weeks thereafter until disease progression; median time on follow-up was 7.3, 7.1, and 8.9 months in each group respectively.
    Notes
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 2 only.
    End point values
    		 Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Number of subjects analysed
    61
    59
    61
    Units: percentage of participants
        number (confidence interval 80%)
    77.0 (68.7 to 84.0)
    59.3 (50.1 to 68.0)
    63.9 (55.0 to 72.2)
    Statistical analysis title
    		 Objective Response Rate of Arm A vs Arm C
    Statistical analysis description
    The analysis of ORR between Arm A versus Arm C was a key secondary endpoint in the testing hierarchy (see details below), and was compared using a two-sided Cochran-Mantel-Haenszel test stratified by LDH level. An odds ratio of > 1 favors Arm A.
    Comparison groups
    Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib v Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [36]
    P-value
    		 = 0.115 [37]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.9
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 1.1
         upper limit
    		 3.2
    Notes
    [36] - If the primary analysis of PFS (Arm A vs Arm C) was statistically significant a fixed sequence testing procedure was to be performed with a 2-sided significance level of 0.2 for the following key secondary endpoints: OS (Arm A vs Arm C) PFS (Arms B vs Arm C) OS (Arm B vs Arm C) ORR (Arm A vs Arm C) ORR (Arm B vs Arm C) If significance versus Arm C was not demonstrated, all endpoints later in the testing hierarchy were to be considered exploratory.
    [37] - Cochran-Mantel-Haenszel test stratified by LDH level.
    Statistical analysis title
    		 Objective Response Rate of Arm B vs Arm C
    Statistical analysis description
    The analysis of ORR between Arm B versus Arm C was a key secondary endpoint in the testing hierarchy (see details below), and was compared using a two-sided Cochran-Mantel-Haenszel test stratified by LDH level. An odds ratio of > 1 favors Arm B.
    Comparison groups
    Phase 2: Placebo + Carboplatin/Etoposide -> Placebo v Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [38]
    P-value
    		 = 0.604 [39]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.8
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 1.3
    Notes
    [38] - If the primary analysis of PFS (Arm A vs Arm C) was statistically significant a fixed sequence testing procedure was to be performed with a 2-sided significance level of 0.2 for the following key secondary endpoints: OS (Arm A vs Arm C) PFS (Arms B vs Arm C) OS (Arm B vs Arm C) ORR (Arm A vs Arm C) ORR (Arm B vs Arm C) If significance versus Arm C was not demonstrated, all endpoints later in the testing hierarchy were to be considered exploratory.
    [39] - Cochran-Mantel-Haenszel test stratified by LDH level.

    Secondary: Phase 1: Number of Participants With Adverse Events

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    End point title
    		 Phase 1: Number of Participants With Adverse Events [40]
    End point description
    The intensity of each adverse event (AE) was assessed utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0, and according to the following: Grade 1 (Mild): AE is transient and easily tolerated by the participant; Grade 2 (Moderate): AE causes the participant discomfort and interrupts the participant's usual activities; Grade 3/4 (Severe): The adverse event causes considerable interference with the participant's usual activities and may be incapacitating or life-threatening; Grade 5: Death. Serious adverse events were those that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in congenital anomaly, or persistent or significant disability/incapacity. The number of participants analyzed includes all participants enrolled in the Phase 1 portion of the study who received at least 1 dose of study treatment.
    End point type
    Secondary
    End point timeframe
    From first dose of any study drug to 30 days after the last dose; the median duration of treatment with veliparib across all groups in Phase 1 was 127.5 days.
    Notes
    [40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint pertains to Phase 1 only.
    End point values
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide
    Number of subjects analysed
    4
    3
    4
    3
    8
    14
    4
    Units: participants
        Any adverse event
    4
    3
    4
    3
    8
    14
    4
        Any AE Grade 3/4
    4
    3
    4
    3
    7
    14
    4
        Any serious adverse event
    3
    1
    3
    2
    3
    6
    3
        Any fatal adverse event
    0
    0
    1
    1
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Deaths are reported from enrollment to end of study, maximum time on follow-up was 26 months. AEs were collected from first dose of study drug until 30 days after last dose; Maximum duration of treatment was 541 days in Phase 1 and 654 days in Phase 2.
    Adverse event reporting additional description
    Adverse events and deaths are reported for all participants who received at least 1 dose of study drug (safety population). One participant randomized in Phase 2 to Arm A died before receiving treatment and was not included in the safety population.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 80 mg veliparib orally twice a day (BID) on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered intravenously (IV) on Day 1 at a target area under the curve (AUC) 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 120 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 160 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 200 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 240 mg veliparib orally BID on Days -2 to 5 (7 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 5 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 240 mg veliparib orally BID on Days -2 to Day 19 (continuous schedule) in combination with carboplatin/etoposide for up to four 21-day cycles. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide
    Reporting group description
    		 Participants received 240 mg veliparib orally BID on Days -2 to 12 (14 days) in combination with carboplatin/etoposide for up to four 21-day cycles, with the exception of Cycle 2, when veliparib was administered on Days 2 to 12 to allow for evaluation of potential impact of veliparib on etoposide pharmacokinetics. Carboplatin was administered IV on Day 1 at a target AUC 5 mg/mL*minute and etoposide 100 mg/m² IV on Days 1 to 3 of every 21-day cycle. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo
    Reporting group description
    		 Participants in Arm B received veliparib 240 mg BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min administered on Day 1, and etoposide 100 mg/m² administered on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression received placebo monotherapy BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib
    Reporting group description
    		 Participants in Arm A received veliparib 240 mg BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min administered on Day 1, and etoposide 100 mg/m² administered on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression continued on veliparib monotherapy at 400 mg BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Reporting group title
    Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Reporting group description
    		 Participants in Arm C received placebo BID on Day -2 to 12 (14-day schedule), carboplatin AUC 5 mg/mL*min on Day 1, and etoposide 100 mg/m² on Days 1 to 3 of each 21-day cycle for up to 6 cycles. Participants without evidence of disease progression received placebo monotherapy BID continuous dosing (21-day cycles) until disease progression or unacceptable toxicity.

    Serious adverse events
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    3 / 4 (75.00%)
    2 / 3 (66.67%)
    3 / 8 (37.50%)
    3 / 4 (75.00%)
    6 / 14 (42.86%)
    39 / 58 (67.24%)
    33 / 60 (55.00%)
    27 / 60 (45.00%)
         number of deaths (all causes)
    0
    0
    1
    1
    0
    0
    0
    45
    49
    41
         number of deaths resulting from adverse events
    0
    0
    1
    1
    0
    0
    0
    10
    7
    5
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    CANCER PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MALIGNANT NEOPLASM PROGRESSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    5 / 58 (8.62%)
    5 / 60 (8.33%)
    5 / 60 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 3
    0 / 1
    METASTASES TO CENTRAL NERVOUS SYSTEM
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    4 / 58 (6.90%)
    2 / 60 (3.33%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 4
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    AORTITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL ARTERY THROMBOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERIPHERAL EMBOLISM
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUPERIOR VENA CAVA SYNDROME
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VENA CAVA THROMBOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHEST PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    2 / 60 (3.33%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEATH
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    DISEASE PROGRESSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FATIGUE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    MALAISE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    2 / 58 (3.45%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUDDEN CARDIAC DEATH
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    SUDDEN DEATH
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY DISTRESS SYNDROME
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ATELECTASIS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    2 / 60 (3.33%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    EPISTAXIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMOPTYSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    3 / 58 (5.17%)
    2 / 60 (3.33%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 4
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    PULMONARY HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Psychiatric disorders
    DEPRESSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    PLATELET COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TRANSAMINASES INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    VASCULAR PROCEDURE COMPLICATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    2 / 60 (3.33%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIAC FAILURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIO-RESPIRATORY ARREST
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SINUS NODE DYSFUNCTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VENTRICULAR TACHYCARDIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    CEREBRAL ISCHAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIZZINESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HEADACHE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ISCHAEMIC STROKE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MIGRAINE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MOTOR DYSFUNCTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TOXIC NEUROPATHY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    3 / 58 (5.17%)
    3 / 60 (5.00%)
    2 / 60 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    1 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    7 / 58 (12.07%)
    5 / 60 (8.33%)
    3 / 60 (5.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    5 / 7
    2 / 5
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LEUKOPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    4 / 58 (6.90%)
    2 / 60 (3.33%)
    2 / 60 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 5
    2 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PANCYTOPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    2 / 60 (3.33%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    6 / 58 (10.34%)
    3 / 60 (5.00%)
    2 / 60 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 9
    1 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DUODENAL ULCER PERFORATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPHAGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTRIC PERFORATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTRITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL INFLAMMATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMATEMESIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    ILEUS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL ISCHAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MOUTH HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PALATAL OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    HEPATIC FAILURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    DIABETES INSIPIDUS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BACK PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BURSITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FLANK PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    ABDOMINAL SEPSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ANAL ABSCESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENCEPHALITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    IMPLANT SITE CELLULITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ORCHITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PLEURAL INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    3 / 58 (5.17%)
    7 / 60 (11.67%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    2 / 10
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    PNEUMONIA INFLUENZAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA LEGIONELLA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    3 / 60 (5.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOKALAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOMAGNESAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    3 / 58 (5.17%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib Phase 2: Placebo + Carboplatin/Etoposide -> Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    3 / 3 (100.00%)
    4 / 4 (100.00%)
    3 / 3 (100.00%)
    8 / 8 (100.00%)
    4 / 4 (100.00%)
    14 / 14 (100.00%)
    53 / 58 (91.38%)
    57 / 60 (95.00%)
    53 / 60 (88.33%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    CANCER PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    MALIGNANT NEOPLASM PROGRESSION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    METASTASES TO CENTRAL NERVOUS SYSTEM
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    1
    0
    Vascular disorders
    HAEMATOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    HOT FLUSH
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    3 / 58 (5.17%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    3
    0
    0
    HYPERTENSION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    4 / 14 (28.57%)
    1 / 58 (1.72%)
    2 / 60 (3.33%)
    3 / 60 (5.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    6
    3
    2
    3
    HYPOTENSION
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    5 / 58 (8.62%)
    1 / 60 (1.67%)
    2 / 60 (3.33%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    1
    5
    1
    2
    INTERMITTENT CLAUDICATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    2 / 14 (14.29%)
    11 / 58 (18.97%)
    9 / 60 (15.00%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    8
    26
    16
    3
    CHEST PAIN
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    3 / 58 (5.17%)
    3 / 60 (5.00%)
    2 / 60 (3.33%)
         occurrences all number
    2
    0
    0
    1
    1
    0
    2
    3
    3
    2
    CREPITATIONS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    CRYING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    FACE OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    FATIGUE
         subjects affected / exposed
    2 / 4 (50.00%)
    3 / 3 (100.00%)
    1 / 4 (25.00%)
    2 / 3 (66.67%)
    6 / 8 (75.00%)
    1 / 4 (25.00%)
    9 / 14 (64.29%)
    16 / 58 (27.59%)
    15 / 60 (25.00%)
    10 / 60 (16.67%)
         occurrences all number
    3
    5
    2
    4
    6
    1
    20
    17
    23
    12
    FEELING ABNORMAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    FEELING COLD
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    3
    0
    0
    GAIT DISTURBANCE
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    0
    1
    4
    0
    1
    0
    1
    0
    0
    2
    INJECTION SITE EXTRAVASATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    INJECTION SITE HAEMATOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    INJECTION SITE PHLEBITIS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    LOSS OF CONTROL OF LEGS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    MALAISE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    2 / 14 (14.29%)
    3 / 58 (5.17%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    3
    3
    0
    0
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    2 / 58 (3.45%)
    2 / 60 (3.33%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    2
    2
    3
    NECROSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    2 / 58 (3.45%)
    1 / 60 (1.67%)
    4 / 60 (6.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    2
    1
    4
    OEDEMA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    3
    1
    0
    0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    2 / 14 (14.29%)
    6 / 58 (10.34%)
    2 / 60 (3.33%)
    5 / 60 (8.33%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    3
    7
    3
    5
    PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    3 / 58 (5.17%)
    4 / 60 (6.67%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    3
    4
    3
    PYREXIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    3 / 14 (21.43%)
    2 / 58 (3.45%)
    6 / 60 (10.00%)
    8 / 60 (13.33%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    3
    2
    9
    10
    SWELLING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    SWELLING FACE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    2
    0
    0
    Immune system disorders
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Reproductive system and breast disorders
    PERINEAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    6
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    ASTHMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    COUGH
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    2 / 4 (50.00%)
    5 / 14 (35.71%)
    5 / 58 (8.62%)
    6 / 60 (10.00%)
    7 / 60 (11.67%)
         occurrences all number
    1
    0
    2
    1
    0
    2
    6
    5
    6
    7
    DYSPHONIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    3 / 58 (5.17%)
    2 / 60 (3.33%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    4
    2
    1
    DYSPNOEA
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    2 / 4 (50.00%)
    5 / 14 (35.71%)
    9 / 58 (15.52%)
    12 / 60 (20.00%)
    7 / 60 (11.67%)
         occurrences all number
    4
    1
    2
    1
    1
    2
    5
    11
    16
    10
    EPISTAXIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    1
    1
    0
    2
    HAEMOPTYSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    2 / 60 (3.33%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    2
    2
    3
    HICCUPS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    0
    0
    1
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    3 / 58 (5.17%)
    1 / 60 (1.67%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    3
    1
    2
    PRODUCTIVE COUGH
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    4 / 58 (6.90%)
    1 / 60 (1.67%)
    3 / 60 (5.00%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    0
    6
    1
    3
    PULMONARY EMBOLISM
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    3 / 60 (5.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    3
    1
    RHINITIS ALLERGIC
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    RHINORRHOEA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    3 / 58 (5.17%)
    1 / 60 (1.67%)
    3 / 60 (5.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    3
    1
    4
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    4 / 58 (6.90%)
    3 / 60 (5.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    0
    4
    3
    0
    CONFUSIONAL STATE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    1
    DELIRIUM
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    DEPRESSION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    0
    0
    1
    0
    HALLUCINATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    INSOMNIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    1 / 4 (25.00%)
    7 / 14 (50.00%)
    5 / 58 (8.62%)
    4 / 60 (6.67%)
    4 / 60 (6.67%)
         occurrences all number
    0
    0
    1
    0
    3
    1
    11
    6
    5
    4
    RESTLESSNESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    TENSION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Product issues
    DEVICE OCCLUSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    3 / 58 (5.17%)
    5 / 60 (8.33%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    6
    5
    10
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    3 / 58 (5.17%)
    5 / 60 (8.33%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    4
    6
    3
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    2 / 60 (3.33%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    2
    3
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    4 / 60 (6.67%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    4
    2
    BLOOD LACTATE DEHYDROGENASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    3 / 60 (5.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    3
    0
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    HLA MARKER STUDY POSITIVE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    INTERNATIONAL NORMALISED RATIO INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    LYMPHOCYTE COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    2 / 4 (50.00%)
    6 / 14 (42.86%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    5
    1
    2
    2
    8
    20
    0
    2
    0
    PLATELET COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    5 / 14 (35.71%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    3
    11
    6
    2
    0
    TRANSAMINASES INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    URINE OUTPUT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    WEIGHT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    5 / 14 (35.71%)
    2 / 58 (3.45%)
    3 / 60 (5.00%)
    7 / 60 (11.67%)
         occurrences all number
    0
    0
    1
    3
    0
    0
    13
    2
    3
    11
    WEIGHT INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    2 / 60 (3.33%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    3
    0
    0
    0
    0
    0
    3
    0
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    2 / 4 (50.00%)
    2 / 14 (14.29%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    3
    2
    2
    5
    0
    Injury, poisoning and procedural complications
    CHEMICAL PHLEBITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    FOREARM FRACTURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    INFUSION RELATED REACTION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    MUSCLE RUPTURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    MUSCLE STRAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    POST PROCEDURAL COMPLICATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    PROCEDURAL HEADACHE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    PROCEDURAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    SKIN ABRASION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    5 / 58 (8.62%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    5
    1
    1
    LEFT VENTRICULAR FAILURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    PALPITATIONS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    3 / 60 (5.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    4
    0
    TACHYCARDIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    1
    1
    Nervous system disorders
    ATAXIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    DISTURBANCE IN ATTENTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    2
    DIZZINESS
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 4 (50.00%)
    3 / 14 (21.43%)
    9 / 58 (15.52%)
    5 / 60 (8.33%)
    3 / 60 (5.00%)
         occurrences all number
    2
    1
    0
    0
    4
    2
    6
    13
    6
    4
    DYSARTHRIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    DYSGEUSIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 4 (50.00%)
    3 / 14 (21.43%)
    4 / 58 (6.90%)
    2 / 60 (3.33%)
    2 / 60 (3.33%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    3
    6
    2
    2
    HEAD DISCOMFORT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    HEADACHE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    3 / 14 (21.43%)
    9 / 58 (15.52%)
    10 / 60 (16.67%)
    7 / 60 (11.67%)
         occurrences all number
    0
    1
    0
    1
    2
    0
    3
    11
    11
    7
    MEMORY IMPAIRMENT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    MUSCLE CONTRACTIONS INVOLUNTARY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    PERIPHERAL MOTOR NEUROPATHY
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    0
    0
    0
    1
    0
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    3 / 60 (5.00%)
    1 / 60 (1.67%)
         occurrences all number
    2
    2
    1
    0
    1
    0
    0
    1
    3
    1
    POLYNEUROPATHY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    PRESYNCOPE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    SOMNOLENCE
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    2
    1
    0
    0
    0
    TREMOR
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    4 / 8 (50.00%)
    2 / 4 (50.00%)
    7 / 14 (50.00%)
    35 / 58 (60.34%)
    35 / 60 (58.33%)
    26 / 60 (43.33%)
         occurrences all number
    3
    1
    9
    3
    11
    6
    18
    105
    104
    55
    DISSEMINATED INTRAVASCULAR COAGULATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    0
    1
    0
    LEUKOPENIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    12 / 58 (20.69%)
    7 / 60 (11.67%)
    3 / 60 (5.00%)
         occurrences all number
    1
    0
    0
    1
    3
    0
    0
    27
    15
    13
    NEUTROPENIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    4 / 8 (50.00%)
    2 / 4 (50.00%)
    8 / 14 (57.14%)
    33 / 58 (56.90%)
    36 / 60 (60.00%)
    28 / 60 (46.67%)
         occurrences all number
    4
    0
    8
    0
    11
    6
    34
    86
    94
    71
    THROMBOCYTOPENIA
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    1 / 4 (25.00%)
    5 / 14 (35.71%)
    23 / 58 (39.66%)
    22 / 60 (36.67%)
    12 / 60 (20.00%)
         occurrences all number
    2
    2
    0
    0
    6
    3
    16
    62
    58
    22
    Ear and labyrinth disorders
    EAR DISCOMFORT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    HYPOACUSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    OTOTOXICITY
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    TINNITUS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    1
    0
    Eye disorders
    BLINDNESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    DRY EYE
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    EYE IRRITATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    EYE PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    LACRIMATION INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    VITREOUS DETACHMENT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    2
    1
    0
    0
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    2 / 60 (3.33%)
    1 / 60 (1.67%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    2
    1
    2
    1
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    2 / 14 (14.29%)
    1 / 58 (1.72%)
    4 / 60 (6.67%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    2
    1
    4
    3
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    1 / 4 (25.00%)
    2 / 14 (14.29%)
    0 / 58 (0.00%)
    2 / 60 (3.33%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    1
    0
    3
    3
    2
    0
    2
    2
    ANAL INFLAMMATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    ASCITES
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    CONSTIPATION
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    0 / 4 (0.00%)
    3 / 14 (21.43%)
    13 / 58 (22.41%)
    14 / 60 (23.33%)
    11 / 60 (18.33%)
         occurrences all number
    2
    1
    1
    0
    4
    0
    4
    19
    17
    15
    DIARRHOEA
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    7 / 14 (50.00%)
    11 / 58 (18.97%)
    8 / 60 (13.33%)
    11 / 60 (18.33%)
         occurrences all number
    1
    1
    4
    0
    0
    1
    11
    21
    11
    12
    DIVERTICULUM
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    DRY MOUTH
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    1 / 4 (25.00%)
    4 / 14 (28.57%)
    3 / 58 (5.17%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    2
    0
    0
    0
    2
    1
    5
    4
    1
    0
    DYSPEPSIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    2 / 58 (3.45%)
    7 / 60 (11.67%)
    4 / 60 (6.67%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    1
    3
    8
    5
    DYSPHAGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    2 / 60 (3.33%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    2
    1
    ENTEROVESICAL FISTULA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    ERUCTATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    2 / 14 (14.29%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    FLATULENCE
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    2 / 14 (14.29%)
    2 / 58 (3.45%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    2
    2
    0
    0
    GASTRITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    1 / 60 (1.67%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    2
    3
    HAEMATOCHEZIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    HAEMORRHOIDS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    LOWER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    NAUSEA
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 3 (66.67%)
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    5 / 8 (62.50%)
    1 / 4 (25.00%)
    9 / 14 (64.29%)
    23 / 58 (39.66%)
    29 / 60 (48.33%)
    21 / 60 (35.00%)
         occurrences all number
    1
    4
    7
    4
    8
    1
    16
    47
    57
    29
    OESOPHAGITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    2
    0
    ORAL DISCOMFORT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    PROCTALGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    PROCTITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    RETCHING
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    2
    0
    0
    0
    STOMATITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    2 / 14 (14.29%)
    2 / 58 (3.45%)
    3 / 60 (5.00%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    3
    2
    4
    4
    VOMITING
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    2 / 14 (14.29%)
    10 / 58 (17.24%)
    13 / 60 (21.67%)
    8 / 60 (13.33%)
         occurrences all number
    2
    2
    4
    2
    2
    1
    3
    12
    20
    9
    Hepatobiliary disorders
    HEPATIC PAIN
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    3 / 8 (37.50%)
    1 / 4 (25.00%)
    8 / 14 (57.14%)
    17 / 58 (29.31%)
    22 / 60 (36.67%)
    18 / 60 (30.00%)
         occurrences all number
    2
    1
    3
    2
    5
    3
    12
    19
    27
    20
    DRY SKIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    1
    0
    1
    ECCHYMOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    ECZEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    HYPERHIDROSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    3 / 14 (21.43%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    4
    0
    1
    0
    NIGHT SWEATS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    1
    PETECHIAE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    PIGMENTATION DISORDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    PRURITUS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    2 / 60 (3.33%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    1
    2
    1
    2
    RASH
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    4 / 60 (6.67%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    4
    2
    RASH MACULAR
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    SKIN ULCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    STICKY SKIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Renal and urinary disorders
    DYSURIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    2
    NOCTURIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    PNEUMATURIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    POST MICTURITION DRIBBLE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    TUBULOINTERSTITIAL NEPHRITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    URINARY HESITATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    URINARY INCONTINENCE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    URINARY RETENTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    1
    2
    1
    Endocrine disorders
    INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    2 / 58 (3.45%)
    6 / 60 (10.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    3
    0
    4
    6
    8
    0
    BACK PAIN
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    2 / 3 (66.67%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    6 / 14 (42.86%)
    7 / 58 (12.07%)
    9 / 60 (15.00%)
    9 / 60 (15.00%)
         occurrences all number
    2
    0
    1
    2
    3
    0
    6
    7
    11
    9
    BONE PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    3 / 60 (5.00%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    1
    0
    2
    1
    0
    1
    3
    3
    COCCYDYNIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    FLANK PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    2 / 60 (3.33%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    1
    0
    1
    2
    GROIN PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    2 / 14 (14.29%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    INTERVERTEBRAL DISC PROTRUSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    MUSCLE SPASMS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    2 / 60 (3.33%)
    0 / 60 (0.00%)
         occurrences all number
    0
    2
    2
    0
    0
    0
    0
    0
    2
    0
    MUSCULAR WEAKNESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    2
    0
    0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    3 / 58 (5.17%)
    5 / 60 (8.33%)
    0 / 60 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    1
    7
    5
    0
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    2 / 14 (14.29%)
    2 / 58 (3.45%)
    3 / 60 (5.00%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    3
    2
    3
    2
    MUSCULOSKELETAL STIFFNESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    MYALGIA
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    2 / 14 (14.29%)
    2 / 58 (3.45%)
    1 / 60 (1.67%)
    4 / 60 (6.67%)
         occurrences all number
    3
    2
    0
    0
    2
    0
    2
    8
    1
    4
    MYOSITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    NECK PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    3 / 60 (5.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    4
    0
    PAIN IN EXTREMITY
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 3 (66.67%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    4 / 14 (28.57%)
    4 / 58 (6.90%)
    1 / 60 (1.67%)
    2 / 60 (3.33%)
         occurrences all number
    1
    2
    2
    0
    0
    1
    6
    4
    2
    2
    PAIN IN JAW
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    SPINAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    1
    TENDON PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    3 / 58 (5.17%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    1
    1
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    CYSTITIS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    GASTROENTERITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    NASOPHARYNGITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    2 / 58 (3.45%)
    2 / 60 (3.33%)
    0 / 60 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    3
    2
    0
    ORAL CANDIDIASIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    4 / 58 (6.90%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    4
    2
    0
    ORAL FUNGAL INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    PNEUMONIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    5 / 60 (8.33%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    5
    3
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    3 / 58 (5.17%)
    1 / 60 (1.67%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    3
    1
    0
    RHINITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    1
    1
    2
    TOOTH ABSCESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    0 / 58 (0.00%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    2 / 14 (14.29%)
    2 / 58 (3.45%)
    0 / 60 (0.00%)
    2 / 60 (3.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    2
    0
    2
    URINARY TRACT INFECTION
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    2 / 58 (3.45%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences all number
    2
    0
    2
    2
    0
    0
    1
    3
    1
    1
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    3 / 4 (75.00%)
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    2 / 4 (50.00%)
    7 / 14 (50.00%)
    12 / 58 (20.69%)
    17 / 60 (28.33%)
    14 / 60 (23.33%)
         occurrences all number
    3
    4
    3
    0
    5
    2
    16
    14
    20
    16
    DEHYDRATION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    3 / 58 (5.17%)
    1 / 60 (1.67%)
    1 / 60 (1.67%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    3
    1
    1
    HYPERGLYCAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    6 / 58 (10.34%)
    1 / 60 (1.67%)
    6 / 60 (10.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    6
    1
    7
    HYPERKALAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 14 (0.00%)
    2 / 58 (3.45%)
    2 / 60 (3.33%)
    3 / 60 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    2
    2
    6
    HYPOCALCAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    3 / 58 (5.17%)
    2 / 60 (3.33%)
    1 / 60 (1.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    2
    1
    HYPOGLYCAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 14 (7.14%)
    1 / 58 (1.72%)
    0 / 60 (0.00%)
    0 / 60 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    HYPOKALAEMIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    9 / 58 (15.52%)
    5 / 60 (8.33%)
    7 / 60 (11.67%)
         occurrences all number
    1
    0
    1
    0
    1
    3
    2
    13
    5
    8
    HYPOMAGNESAEMIA
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    1 / 4 (25.00%)
    4 / 14 (28.57%)
    7 / 58 (12.07%)
    10 / 60 (16.67%)
    9 / 60 (15.00%)
         occurrences all number
    1
    1
    0
    0
    3
    1
    5
    9
    24
    12
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    1 / 14 (7.14%)
    7 / 58 (12.07%)
    6 / 60 (10.00%)
    4 / 60 (6.67%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    3
    7
    8
    5
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 14 (0.00%)
    1 / 58 (1.72%)
    1 / 60 (1.67%)
    5 / 60 (8.33%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    1
    6

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 May 2015
    Allowed any advanced/metastatic solid tumors for which carboplatin/etoposide is appropriate. Changed window for baseline radiographic tumor assessments from 14 days to 21 days. Clarified plan for replacement of subjects in the Phase 1 dose-escalation portion of the study. Updated the statistical analysis for Phase 2 and clarified plan for discontinuation of Phase 2 subjects from treatment vs. study. Added DMC to Phase 2 portion of the study.
    30 Jul 2015
    Clarified enrollment and timing of dose escalations during the Phase 1 portion of the study and allow for additional subjects for safety expansion at the RPTD. Clarified PK sampling schedule. Corrected the time of contraceptive use following the last dose of the study drug.
    18 Dec 2015
    Added additional DLT criteria and updated the total number of subjects in the Phase 1 dose-escalation portion of the study. Updated language around new veliparib dosing schedules. Added language to allow for Phase 2 subjects who discontinued carboplatin and etoposide due to toxicity but not disease progression to transition to monotherapy veliparib or placebo. Updated the length of time that subjects were followed on study to "until disease progression."
    14 Jun 2016
    Increased total number of carboplatin, etoposide and veliparib cycles for Phase 2 subjects. Changed Cycle 5 to Maintenance for Phase 2. Increased total number of subjects and sites.
    22 Nov 2016
    Added veliparib/placebo RPTD of 240 mg BID in a 14-day schedule as the veliparib/placebo dose and schedule for Phase 2 combination therapy.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/30327308
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    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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