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    Clinical Trial Results:
    A Phase 3 Placebo-Controlled Study of Carboplatin/Paclitaxel With or Without Concurrent and Continuation Maintenance Veliparib (PARP Inhibitor) in Subjects With Previously Untreated Stages III or IV High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Summary
    EudraCT number
    		 2014-005070-11
    Trial protocol
    		 DK   ES   PL  
    Global end of trial date
    05 Oct 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Oct 2024
    First version publication date
    18 Oct 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    M13-694
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02470585
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co. KG
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
    Public contact
    Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
    Scientific contact
    Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 Oct 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Oct 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to evaluate whether progression-free survival (PFS) was prolonged with the addition of veliparib to standard platinum-based chemotherapy (carboplatin/paclitaxel [C/P]) and continued as maintenance therapy compared with chemotherapy alone. The study was terminated early (business decision not related to patient safety).
    Protection of trial subjects
    Subjects signed and dated an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Jul 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 75
    Country: Number of subjects enrolled
    Brazil: 11
    Country: Number of subjects enrolled
    Denmark: 5
    Country: Number of subjects enrolled
    Israel: 33
    Country: Number of subjects enrolled
    Japan: 78
    Country: Number of subjects enrolled
    Korea, Republic of: 70
    Country: Number of subjects enrolled
    Poland: 2
    Country: Number of subjects enrolled
    Spain: 46
    Country: Number of subjects enrolled
    United Kingdom: 27
    Country: Number of subjects enrolled
    United States: 793
    Worldwide total number of subjects
    1140
    EEA total number of subjects
    53
    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)
    686
    From 65 to 84 years
    448
    85 years and over
    6

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants were randomized in a 1:1:1 ratio to one of three treatment groups. Randomization was stratified according to the timing of surgery and residual disease after primary surgery or interval surgery, the paclitaxel schedule, stage of disease, geographic region, and germline breast cancer susceptibility gene (BRCA) mutation status.

    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
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo + Carboplatin + Paclitaxel -> Placebo
    Arm description
    		 Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion, either 80 mg/m² of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle (weekly dosing), or 175 mg/m² of BSA on Day 1 of each 21-day cycle (3-week dosing).

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion at an area under the curve (AUC) of 6 mg/mL/min every 3 weeks.

    Investigational medicinal product name
    Placebo to Veliparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules for oral administration

    Arm title
    		 Veliparib + Carboplatin + Paclitaxel -> Placebo
    Arm description
    		 Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks, and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    Other name
    ABT-888
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules for oral administration

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion at an area under the curve (AUC) of 6 mg/mL/min every 3 weeks.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion, either 80 mg/m² of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle (weekly dosing), or 175 mg/m² of BSA on Day 1 of each 21-day cycle (3-week dosing).

    Investigational medicinal product name
    Placebo to Veliparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules for oral administration

    Arm title
    		 Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Arm description
    		 Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks, and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Veliparib
    Investigational medicinal product code
    Other name
    ABT-888
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Capsules for oral administration

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion at an area under the curve (AUC) of 6 mg/mL/min every 3 weeks.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered by intravenous infusion, either 80 mg/m² of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle (weekly dosing), or 175 mg/m² of BSA on Day 1 of each 21-day cycle (3-week dosing).

    Number of subjects in period 1
    		Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Started
    375
    383
    382
    Completed
    0
    0
    0
    Not completed
    375
    383
    382
         Death
    224
    227
    199
         Other, not specified
    5
    7
    14
         Missing due to site non-compliance
    -
    2
    3
         Lost to follow-up
    8
    15
    13
         Withdrew consent
    21
    22
    31
         Sponsor discontinued study
    117
    110
    122

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo + Carboplatin + Paclitaxel -> Placebo
    Reporting group description
    		 Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

    Reporting group title
    Veliparib + Carboplatin + Paclitaxel -> Placebo
    Reporting group description
    		 Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks, and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

    Reporting group title
    Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Reporting group description
    		 Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks, and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

    Reporting group values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib Total
    Number of subjects
    		 375 383 382 1140
    Age categorical
    Units: Subjects
        < 65 years
    		 233 226 228 687
        ≥ 65 years
    		 142 157 154 453
    Age continuous
    Units: years
        median (full range (min-max))
    		 62.0 (33.0 to 86.0) 62.0 (22.0 to 88.0) 62.0 (30.0 to 85.0) -
    Gender categorical
    Units: Subjects
        Female
    		 375 383 382 1140
        Male
    		 0 0 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 28 27 26 81
        Not Hispanic or Latino
    		 347 356 356 1059
        Unknown or Not Reported
    		 0 0 0 0
    Race/Ethnicity
    Units: Subjects
        White
    		 299 297 300 896
        Black or African American
    		 10 13 20 43
        Asian
    		 59 69 56 184
        American Indian or Alaska Native
    		 1 1 1 3
        Native Hawaiian or other Pacific Islander
    		 1 0 2 3
        Multi-race
    		 3 0 0 3
        Missing
    		 2 3 3 8
    Geographic Region
    Units: Subjects
        North America
    		 266 261 267 794
        Japan
    		 23 30 25 78
        Rest of World
    		 86 92 90 268
    BRCA-Deficient Status
    The BRCA-mutation cohort was defined as participants who had deleterious or suspected deleterious germline (gBRCA) or tissue-based (tBRCA) mutations as determined by the Myriad BRACAnalysis® companion diagnostic (CDx) or myChoice® HRD CDx assay, respectively, in BRCA1 or BRCA2.
    Units: Subjects
        Germline or tissue BRCA1/2 mutation
    		 92 98 108 298
        Germline or tissue BRCA1/2 wildtype
    		 254 243 245 742
        Missing
    		 29 42 29 100
    Homologous Recombination Deficiency (HRD) Status
    The HRD cohort consisted of participants who had tumors that were BRCA-mutated or had HRD according to the Myriad myChoice® assay, on which a score of ≥33 was considered to indicate HRD status, and a score of < 33 was considered to indicate non-HRD status.
    Units: Subjects
        HRD
    		 207 206 214 627
        Non-HRD
    		 124 123 125 372
        Missing
    		 44 54 43 141
    Stage of Disease
    Staging of primary ovarian carcinomas according to the International Federation of Gynecology and Obstetrics (FIGO) criteria, based on clinical examination, surgical exploration, histologic characteristics and cytologic testing. STAGE III: Tumor involves 1 or both ovaries with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastases to the retroperitoneal lymph nodes. STAGE IV: Distant metastases excluding peritoneal metastases
    Units: Subjects
        Stage III
    		 292 288 295 875
        Stage IV
    		 82 94 87 263
        Missing
    		 1 1 0 2
    Type of Surgery Received
    Cytoreductive surgery could be performed before randomization and the initiation of study treatment (primary) or after 3 cycles of study treatment (interval), determined at the discretion of the investigator.
    Units: Subjects
        Primary
    		 250 253 261 764
        Interval
    		 107 114 99 320
        No surgery received
    		 18 16 22 56
    Residual Disease After Primary Surgery
    Data were collected after interval surgery after cycle 3.
    Units: Subjects
        No residual disease
    		 116 118 124 358
        Microscopic residual disease only
    		 58 46 54 158
        Any macroscopic residual disease
    		 76 89 83 248
        Did not undergo primary surgery
    		 125 130 121 376
    Residual Disease After Interval Surgery
    Units: Subjects
        No residual disease
    		 50 46 45 141
        Microscopic residual disease only
    		 22 30 24 76
        Any macroscopic residual disease
    		 31 34 27 92
        Missing
    		 4 4 3 11
        Did not undergo interval surgery
    		 268 269 283 820
    Paclitaxel Dosing Regimen
    Units: Subjects
        Weekly
    		 193 203 190 586
        Every 3 weeks
    		 179 178 189 546
        Missing
    		 3 2 3 8
    Germline BRCA Status
    Units: Subjects
        Germline BRCA1/2 mutation
    		 63 71 80 214
        Germline BRCA1/2 wildtype
    		 305 305 298 908
        Missing
    		 7 7 4 18

    End points

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    End points reporting groups
    Reporting group title
    Placebo + Carboplatin + Paclitaxel -> Placebo
    Reporting group description
    		 Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve [AUC] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

    Reporting group title
    Veliparib + Carboplatin + Paclitaxel -> Placebo
    Reporting group description
    		 Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks, and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

    Reporting group title
    Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Reporting group description
    		 Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks, and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

    Primary: Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 3 vs Arm 1)

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    End point title
    		 Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 3 vs Arm 1)
    End point description
    PFS: time from date subject was randomized to date subject experienced an event of disease progression, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria v 1.1 (as determined by investigator) or to date of death if disease progression wasn’t reached. If subject didn’t have an event of disease progression/death prior to analysis cut-off date, their data were censored at date of last evaluable disease assessment. PFS was estimated using the Kaplan–Meier method, when protocol-specified number of PFS events was reached. Progressive Disease (PD): At least a 20% increase in size of target lesions, compared with smallest size recorded since Tx began, and an absolute increase of ≥5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. Analysis Population: subjects with either a gBRCA and/or tBRCA deleterious or suspected deleterious mutation in BRCA1 or BRCA2 99999 in table below = can't be estimated due to low no. of events
    End point type
    Primary
    End point timeframe
    From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    92
    98
    108
    Units: months
        median (confidence interval 95%)
    22.0 (17.8 to 29.1)
    21.1 (17.0 to 25.5)
    34.7 (31.8 to 99999)
    Statistical analysis title
    		 Arm 3 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Veliparib vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status and disease stage. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient population, HRD population, and ITT population), and multiple endpoints.
    Comparison groups
    Placebo + Carboplatin + Paclitaxel -> Placebo v Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [1]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.435
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.277
         upper limit
    		 0.683
    Notes
    [1] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary endpoints sequentially through the secondary endpoints. A 2-sided p-value of ≤0.05 was considered statistically significant.

    Primary: Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 3 vs Arm 1)

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    End point title
    		 Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 3 vs Arm 1)
    End point description
    PFS: time from date subject was randomized to date subject experienced an event of disease progression, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria v 1.1 (as determined by investigator) or to date of death if disease progression wasn’t reached. If subject didn’t have an event of disease progression/death prior to analysis cut-off date, their data were censored at date of last evaluable disease assessment. PFS was estimated using the Kaplan–Meier method, when protocol-specified number of PFS events was reached. Progressive Disease (PD): At least a 20% increase in size of target lesions, compared with smallest size recorded since Tx began, and an absolute increase of ≥5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. Analysis Population: HRD cohort including those in the BRCA-mutation cohort and those with HRD tumors
    End point type
    Primary
    End point timeframe
    From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    207
    206
    214
    Units: months
        median (confidence interval 95%)
    20.5 (17.8 to 22.8)
    18.1 (16.4 to 22.7)
    31.9 (25.8 to 38.0)
    Statistical analysis title
    		 Arm 3 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Veliparib vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status and disease stage. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient population, HRD population, and ITT population), and multiple endpoints.
    Comparison groups
    Placebo + Carboplatin + Paclitaxel -> Placebo v Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects included in analysis
    421
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [2]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.572
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.433
         upper limit
    		 0.756
    Notes
    [2] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary endpoints sequentially through the secondary endpoints. A 2-sided p-value of ≤0.05 was considered statistically significant.

    Primary: Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 3 vs Arm 1)

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    End point title
    		 Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 3 vs Arm 1)
    End point description
    PFS: time from date subject was randomized to date subject experienced an event of disease progression, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria v 1.1 (as determined by investigator) or to date of death if disease progression wasn’t reached. If subject didn’t have an event of disease progression/death prior to analysis cut-off date, their data were censored at date of last evaluable disease assessment. PFS was estimated using the Kaplan–Meier method, when protocol-specified number of PFS events was reached. Progressive Disease (PD): At least a 20% increase in size of target lesions, compared with smallest size recorded since Tx began, and an absolute increase of ≥5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. Analysis Population: ITT population (all randomized subjects)
    End point type
    Primary
    End point timeframe
    From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    375
    383
    382
    Units: months
        median (confidence interval 95%)
    17.3 (15.1 to 19.1)
    15.2 (14.1 to 17.3)
    23.5 (19.3 to 26.3)
    Statistical analysis title
    		 Arm 3 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Veliparib vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status, disease stage, paclitaxel dosing regimen, and BRCA-mutation status. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient population, HRD population, and ITT populations), and multiple endpoints.
    Comparison groups
    Veliparib + Carboplatin + Paclitaxel -> Veliparib v Placebo + Carboplatin + Paclitaxel -> Placebo
    Number of subjects included in analysis
    757
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [3]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.683
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.562
         upper limit
    		 0.831
    Notes
    [3] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary endpoints sequentially through the secondary endpoints. A 2-sided p-value of ≤0.05 was considered statistically significant.

    Secondary: Overall Survival (OS) in the BRCA-deficient Population

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    End point title
    		 Overall Survival (OS) in the BRCA-deficient Population
    End point description
    OS is defined as the time from the day the participant was randomized to the date of death, and was calculated using Kaplan-Meier methods. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive. Analysis population: BRCA-Deficient population: All randomized participants with germline and/or tissue deleterious/suspected deleterious BRCA1/2 mutation -99999 and 99999 in the table below indicates could not be estimated due to the low number of events.
    End point type
    Secondary
    End point timeframe
    From the time of randomization to the end of the study, up to 98 months
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    92
    98
    108
    Units: months
        median (confidence interval 95%)
    89.5 (83.3 to 99999)
    99999 (69.3 to 99999)
    99999 (-99999 to 99999)
    Statistical analysis title
    		 Arm 3 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Veliparib vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status and disease stage. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient population, HRD population, and ITT population), and multiple endpoints.
    Comparison groups
    Placebo + Carboplatin + Paclitaxel -> Placebo v Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.328 [4]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.567
         upper limit
    		 1.429
    Notes
    [4] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary endpoints sequentially through the secondary endpoints.
    Statistical analysis title
    		 Arm 2 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Placebo vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status and disease stage. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient population, HRD population, and ITT population), and multiple endpoints.
    Comparison groups
    Veliparib + Carboplatin + Paclitaxel -> Placebo v Placebo + Carboplatin + Paclitaxel -> Placebo
    Number of subjects included in analysis
    190
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.808 [5]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.218
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.903
    Notes
    [5] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary endpoints sequentially through the secondary endpoints.

    Secondary: Overall Survival (OS) in the Homologous Recombination Deficiency Population

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    End point title
    		 Overall Survival (OS) in the Homologous Recombination Deficiency Population
    End point description
    OS is defined as the time from the day the participant was randomized to the date of death, and was calculated using Kaplan-Meier methods. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive. Analysis population: All randomized participants considered BRCA-Deficient and those determined to have HRD tumors based on HRD score 99999 in the table below indicates could not be estimated due to the low number of events.
    End point type
    Secondary
    End point timeframe
    From the time of randomization to the end of the study, up to 98 months
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    207
    206
    214
    Units: months
        median (confidence interval 95%)
    71.5 (59.6 to 87.6)
    74.4 (65.4 to 99999)
    99999 (73.8 to 99999)
    Statistical analysis title
    		 Arm 3 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Veliparib vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status and disease stage. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient population, HRD population, and ITT population), and multiple endpoints.
    Comparison groups
    Placebo + Carboplatin + Paclitaxel -> Placebo v Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects included in analysis
    421
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.116 [6]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.844
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.114
    Notes
    [6] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary endpoints sequentially through the secondary endpoints.
    Statistical analysis title
    		 Arm 2 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Placebo vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status and disease stage. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient population, HRD population, and ITT population), and multiple endpoints.
    Comparison groups
    Placebo + Carboplatin + Paclitaxel -> Placebo v Veliparib + Carboplatin + Paclitaxel -> Placebo
    Number of subjects included in analysis
    413
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.352 [7]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.949
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.726
         upper limit
    		 1.242
    Notes
    [7] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary endpoints sequentially through the secondary endpoints.

    Secondary: Overall Survival (OS) in the Whole Population

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    End point title
    		 Overall Survival (OS) in the Whole Population
    End point description
    OS is defined as the time from the day the participant was randomized to the date of death, and was calculated using Kaplan-Meier methods. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive. Analysis population: All randomized participants
    End point type
    Secondary
    End point timeframe
    From the time of randomization to the end of the study, up to 98 months
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    375
    383
    382
    Units: months
        median (confidence interval 95%)
    57.8 (52.3 to 63.8)
    58.0 (50.6 to 64.1)
    59.2 (52.1 to 68.2)
    Statistical analysis title
    		 Arm 3 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Veliparib vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status, disease stage, choice of paclitaxel dosing regimen, and BRCA-mutation status. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient, HRD, and ITT populations), and multiple endpoints.
    Comparison groups
    Placebo + Carboplatin + Paclitaxel -> Placebo v Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects included in analysis
    757
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.283 [8]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.946
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.782
         upper limit
    		 1.144
    Notes
    [8] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary efficacy endpoints sequentially through the secondary efficacy endpoints.
    Statistical analysis title
    		 Arm 2 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Placebo vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status, disease stage, choice of paclitaxel dosing regimen, and BRCA-mutation status. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient, HRD, and ITT populations), and multiple endpoints.
    Comparison groups
    Placebo + Carboplatin + Paclitaxel -> Placebo v Veliparib + Carboplatin + Paclitaxel -> Placebo
    Number of subjects included in analysis
    758
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.638 [9]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.034
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.859
         upper limit
    		 1.244
    Notes
    [9] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary efficacy endpoints sequentially through the secondary efficacy endpoints.

    Secondary: Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population

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    End point title
    		 Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population
    End point description
    The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index–18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement. Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate. DRS was not included in the fixed-sequence testing procedure. Analysis population: BRCA-mutation population, participants with available data at each time point
    End point type
    Secondary
    End point timeframe
    Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    92
    98
    108
    Units: score on a scale
    least squares mean (standard error)
        Cycle 3 (n=87, 84, 92)
    1.8 ( 0.52 )
    0.5 ( 0.53 )
    0.9 ( 0.51 )
        Cycle 5 (n=81, 80, 84)
    1.7 ( 0.57 )
    0.7 ( 0.58 )
    0.3 ( 0.56 )
        Cycle 7 (n=78, 84, 83)
    2.6 ( 0.55 )
    1.8 ( 0.54 )
    1.8 ( 0.54 )
        Cycle 9 (n=79, 80, 80)
    3.3 ( 0.60 )
    3.3 ( 0.60 )
    2.4 ( 0.59 )
        Cycle 11 (n=73, 81, 82)
    3.2 ( 0.56 )
    3.6 ( 0.55 )
    2.9 ( 0.54 )
        Cycle 13 (n=74, 80, 70)
    3.6 ( 0.57 )
    3.8 ( 0.57 )
    3.0 ( 0.57 )
        Cycle 15 (n=69, 63, 69)
    4.3 ( 0.53 )
    4.0 ( 0.54 )
    3.4 ( 0.52 )
        Cycle 17 (n=64, 66, 70)
    3.8 ( 0.56 )
    4.0 ( 0.57 )
    3.2 ( 0.55 )
        Cycle 19 (n=58, 53, 66)
    4.0 ( 0.62 )
    4.0 ( 0.63 )
    2.7 ( 0.59 )
        Cycle 21 (n=55, 56, 72)
    4.6 ( 0.59 )
    3.9 ( 0.59 )
    3.2 ( 0.55 )
        Cycle 23 (n=48, 47, 59)
    4.2 ( 0.55 )
    4.0 ( 0.56 )
    2.8 ( 0.52 )
        Cycle 25 (n=48, 45, 58)
    4.0 ( 0.58 )
    5.0 ( 0.60 )
    3.5 ( 0.55 )
        Cycle 27 (n=41, 42, 53)
    4.5 ( 0.56 )
    4.8 ( 0.56 )
    3.0 ( 0.52 )
        Cycle 29 (n=41, 39, 60)
    4.0 ( 0.66 )
    5.3 ( 0.66 )
    2.9 ( 0.59 )
        Cycle 31 (n=36, 36, 51)
    4.8 ( 0.57 )
    4.8 ( 0.58 )
    2.9 ( 0.52 )
        Cycle 33 (n=38, 38, 58)
    3.9 ( 0.66 )
    5.1 ( 0.67 )
    3.9 ( 0.59 )
        Cycle 35 (n=37, 37, 52)
    4.5 ( 0.61 )
    5.0 ( 0.62 )
    3.2 ( 0.56 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population

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    End point title
    		 Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population
    End point description
    The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index–18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement. Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate. DRS was not included in the fixed-sequence testing procedure. Analysis population: HRD population, participants with available data at each time point
    End point type
    Secondary
    End point timeframe
    Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    207
    206
    214
    Units: score on a scale
    least squares mean (standard error)
        Cycle 3 (n=187, 179, 186)
    1.5 ( 0.35 )
    0.5 ( 0.36 )
    0.9 ( 0.35 )
        Cycle 5 (n=178, 169, 172)
    1.7 ( 0.37 )
    1.1 ( 0.37 )
    0.8 ( 0.37 )
        Cycle 7 (n=172, 168, 170)
    2.4 ( 0.35 )
    1.8 ( 0.36 )
    2.2 ( 0.35 )
        Cycle 9 (n=173, 165, 165)
    3.3 ( 0.37 )
    3.6 ( 0.38 )
    2.3 ( 0.38 )
        Cycle 11 (n=162, 161, 159)
    3.5 ( 0.36 )
    3.5 ( 0.36 )
    2.7 ( 0.36 )
        Cycle 13 (n=160, 159, 134)
    3.6 ( 0.37 )
    3.8 ( 0.38 )
    2.7 ( 0.39 )
        Cycle 15 (n=149, 138, 130)
    4.2 ( 0.35 )
    3.9 ( 0.36 )
    3.3 ( 0.37 )
        Cycle 17 (n=139, 129, 124)
    3.9 ( 0.39 )
    3.4 ( 0.40 )
    3.0 ( 0.40 )
        Cycle 19 (n=120, 107, 119)
    4.2 ( 0.40 )
    3.7 ( 0.42 )
    2.7 ( 0.41 )
        Cycle 21 (n=115, 110, 118)
    4.6 ( 0.40 )
    3.6 ( 0.41 )
    3.0 ( 0.40 )
        Cycle 23 (n=105, 95, 103)
    4.1 ( 0.38 )
    3.6 ( 0.39 )
    3.1 ( 0.38 )
        Cycle 25 (n=99, 86, 96)
    4.1 ( 0.40 )
    4.4 ( 0.41 )
    3.5 ( 0.40 )
        Cycle 27 (n=88, 81, 87)
    4.4 ( 0.39 )
    4.4 ( 0.40 )
    3.0 ( 0.38 )
        Cycle 29 (n=86, 76, 96)
    4.2 ( 0.43 )
    4.7 ( 0.44 )
    3.2 ( 0.41 )
        Cycle 31 (n=78, 73, 82)
    3.9 ( 0.41 )
    4.3 ( 0.42 )
    3.3 ( 0.40 )
        Cycle 33 (n=73, 74, 89)
    4.2 ( 0.45 )
    4.7 ( 0.45 )
    3.9 ( 0.42 )
        Cycle 35 (n=68, 69, 78)
    4.1 ( 0.44 )
    4.6 ( 0.45 )
    3.4 ( 0.43 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population

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    End point title
    		 Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population
    End point description
    The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index–18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement. Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease, stage of disease, choice of paclitaxel dosing regimen and BRCA-deficient status, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate. DRS was not included in the fixed-sequence testing procedure. Analysis population: All randomized participants with available data at each time point
    End point type
    Secondary
    End point timeframe
    Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    375
    383
    382
    Units: score on a scale
    least squares mean (standard error)
        Cycle 3 (n=333, 332, 320)
    1.5 ( 0.28 )
    0.4 ( 0.28 )
    0.9 ( 0.28 )
        Cycle 5 (n=310, 312, 301)
    1.6 ( 0.29 )
    0.9 ( 0.29 )
    0.8 ( 0.29 )
        Cycle 7 (n=300, 301, 287)
    2.3 ( 0.29 )
    1.8 ( 0.29 )
    2.1 ( 0.29 )
        Cycle 9 (n=291, 290, 277)
    3.3 ( 0.29 )
    3.8 ( 0.29 )
    2.4 ( 0.29 )
        Cycle 11 (n=270, 267, 249)
    3.5 ( 0.29 )
    4.0 ( 0.28 )
    3.0 ( 0.29 )
        Cycle 13 (n=254, 254, 225)
    3.8 ( 0.30 )
    4.0 ( 0.30 )
    3.2 ( 0.30 )
        Cycle 15 (n=224, 226, 207)
    4.2 ( 0.30 )
    3.8 ( 0.30 )
    3.3 ( 0.30 )
        Cycle 17 (n=204, 203, 202)
    4.1 ( 0.32 )
    3.7 ( 0.32 )
    3.4 ( 0.32 )
        Cycle 19 (n=177, 171, 178)
    4.4 ( 0.32 )
    4.0 ( 0.32 )
    3.1 ( 0.32 )
        Cycle 21 (n=170, 160, 174)
    4.3 ( 0.34 )
    3.6 ( 0.34 )
    3.3 ( 0.33 )
        Cycle 23 (n=151, 139, 154)
    4.0 ( 0.33 )
    3.9 ( 0.33 )
    3.3 ( 0.32 )
        Cycle 25 (n=145, 127, 145)
    4.0 ( 0.34 )
    4.1 ( 0.35 )
    3.5 ( 0.33 )
        Cycle 27 (n=129, 120, 130)
    4.4 ( 0.33 )
    4.2 ( 0.34 )
    3.5 ( 0.32 )
        Cycle 29 (n=123, 114, 136)
    4.4 ( 0.34 )
    4.4 ( 0.35 )
    3.4 ( 0.33 )
        Cycle 31 (n=112, 109, 120)
    4.0 ( 0.36 )
    4.2 ( 0.37 )
    3.3 ( 0.35 )
        Cycle 33 (n=106, 105, 123)
    4.1 ( 0.38 )
    4.4 ( 0.38 )
    3.7 ( 0.36 )
        Cycle 35 (n=99, 100, 111)
    4.4 ( 0.37 )
    4.2 ( 0.37 )
    3.7 ( 0.35 )
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 2 vs Arm 1)

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    End point title
    		 Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 2 vs Arm 1)
    End point description
    PFS: time from date subject was randomized to date subject experienced an event of disease progression, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria v 1.1 (as determined by investigator) or to date of death if disease progression wasn’t reached. If subject didn’t have an event of disease progression/death prior to analysis cut-off date, their data were censored at date of last evaluable disease assessment. PFS was estimated using the Kaplan–Meier method, when protocol specified number of PFS events was reached. Progressive Disease (PD): At least a 20% increase in size of target lesions, compared with smallest size recorded since Tx began, and an absolute increase of ≥5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. Analysis Population: subjects with either a gBRCA and/or tBRCA deleterious or suspected deleterious mutation in BRCA1 or BRCA2 99999 in table below = can't be estimated due to low no. of events
    End point type
    Secondary
    End point timeframe
    From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    92
    98
    108
    Units: months
        median (confidence interval 95%)
    22.0 (17.8 to 29.1)
    21.1 (17.0 to 25.5)
    34.7 (31.8 to 99999)
    Statistical analysis title
    		 Arm 2 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Placebo vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status and disease stage. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient population, HRD population, and ITT population), and multiple endpoints.
    Comparison groups
    Placebo + Carboplatin + Paclitaxel -> Placebo v Veliparib + Carboplatin + Paclitaxel -> Placebo
    Number of subjects included in analysis
    190
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.335 [10]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.215
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.821
         upper limit
    		 1.799
    Notes
    [10] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary endpoints sequentially through the secondary endpoints.

    Secondary: Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 2 vs Arm 1)

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    End point title
    		 Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 2 vs Arm 1)
    End point description
    PFS: time from date subject was randomized to date subject experienced an event of disease progression, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria v 1.1 (as determined by investigator) or to date of death if disease progression wasn’t reached. If subject didn’t have an event of disease progression/death prior to analysis cut-off date, their data were censored at date of last evaluable disease assessment. PFS was estimated using the Kaplan–Meier method, when protocol- specified number of PFS events was reached. Progressive Disease (PD): At least a 20% increase in size of target lesions, compared with smallest size recorded since Tx began, and an absolute increase of ≥5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. Analysis Population: HRD cohort including those in the BRCA-mutation cohort and those with HRD tumors
    End point type
    Secondary
    End point timeframe
    From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    207
    206
    214
    Units: months
        median (confidence interval 95%)
    20.5 (17.8 to 22.8)
    18.1 (16.4 to 22.7)
    31.9 (25.8 to 38.0)
    Statistical analysis title
    		 Arm 2 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Placebo vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status and disease stage. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient population, HRD population, and ITT population), and multiple endpoints.
    Comparison groups
    Placebo + Carboplatin + Paclitaxel -> Placebo v Veliparib + Carboplatin + Paclitaxel -> Placebo
    Number of subjects included in analysis
    413
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.462 [11]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.855
         upper limit
    		 1.414
    Notes
    [11] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary endpoints sequentially through the secondary endpoints.

    Secondary: Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 2 vs Arm 1)

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    End point title
    		 Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 2 vs Arm 1)
    End point description
    PFS: time from date subject was randomized to date subject experienced an event of disease progression, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria v 1.1 (as determined by investigator) or to date of death if disease progression wasn’t reached. If subject didn’t have an event of disease progression/death prior to analysis cut-off date, their data were censored at date of last evaluable disease assessment. PFS was estimated using the Kaplan–Meier method, when protocol-specified number of PFS events was reached. Progressive Disease (PD): At least a 20% increase in size of target lesions, compared with smallest size recorded since Tx began, and an absolute increase of ≥5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. Analysis Population: ITT population (all randomized subjects)
    End point type
    Secondary
    End point timeframe
    From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
    End point values
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Number of subjects analysed
    375
    383
    382
    Units: months
        median (confidence interval 95%)
    17.3 (15.1 to 19.1)
    15.2 (14.1 to 17.3)
    23.5 (19.3 to 26.3)
    Statistical analysis title
    		 Arm 2 versus Arm 1
    Statistical analysis description
    Analysis for Veliparib + Carboplatin + Paclitaxel -> Placebo vs. Placebo + Carboplatin + Paclitaxel -> Placebo was stratified by residual disease status, disease stage, paclitaxel dosing regimen, and BRCA-mutation status. Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-deficient population, HRD population, and ITT populations), and multiple endpoints.
    Comparison groups
    Placebo + Carboplatin + Paclitaxel -> Placebo v Veliparib + Carboplatin + Paclitaxel -> Placebo
    Number of subjects included in analysis
    758
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.45 [12]
    Method
    		 Log Rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.073
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.895
         upper limit
    		 1.287
    Notes
    [12] - A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary endpoints sequentially through the secondary endpoints.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality and adverse events were collected from the time informed consent was signed through the end of the study.
    Adverse event reporting additional description
    Median time on follow-up was 81.7 months for the Placebo + Carboplatin + Paclitaxel -> Placebo group, 81.2 months for the Veliparib + Carboplatin + Paclitaxel -> Placebo group, and 81.1 months for the Veliparib + Carboplatin + Paclitaxel -> Veliparib group.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Placebo + Carboplatin + Paclitaxel -> Placebo
    Reporting group description
    		 Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve (AUC) of 6 milligrams per milliliter per minute (mg/mL/min) every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

    Reporting group title
    Veliparib + Carboplatin + Paclitaxel -> Veliparib
    Reporting group description
    		 Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks, and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received single-agent\ veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy.

    Reporting group title
    Veliparib + Carboplatin + Paclitaxel -> Placebo
    Reporting group description
    		 Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks, and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles. Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy.

    Serious adverse events
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib Veliparib + Carboplatin + Paclitaxel -> Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    143 / 375 (38.13%)
    146 / 382 (38.22%)
    130 / 383 (33.94%)
         number of deaths (all causes)
    228
    209
    234
         number of deaths resulting from adverse events
    6
    11
    9
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ACUTE MYELOID LEUKAEMIA
         subjects affected / exposed
    0 / 375 (0.00%)
    2 / 382 (0.52%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    MALIGNANT NEOPLASM PROGRESSION
         subjects affected / exposed
    14 / 375 (3.73%)
    5 / 382 (1.31%)
    11 / 383 (2.87%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 6
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 4
    MALIGNANT PLEURAL EFFUSION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    METASTASES TO CENTRAL NERVOUS SYSTEM
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYELODYSPLASTIC SYNDROME
         subjects affected / exposed
    0 / 375 (0.00%)
    2 / 382 (0.52%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEOPLASM MALIGNANT
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    OVARIAN CANCER
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Vascular disorders
    THROMBOPHLEBITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VENOUS THROMBOSIS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUBCLAVIAN VEIN THROMBOSIS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    2 / 375 (0.53%)
    4 / 382 (1.05%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EMBOLISM
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    JUGULAR VEIN THROMBOSIS
         subjects affected / exposed
    2 / 375 (0.53%)
    2 / 382 (0.52%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LYMPHOCELE
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PHLEBITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    CHEST PAIN
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ASTHENIA
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHEST DISCOMFORT
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    IMPLANT SITE EXTRAVASATION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INCARCERATED HERNIA
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    1 / 375 (0.27%)
    4 / 382 (1.05%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PAIN
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PELVIC MASS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    6 / 375 (1.60%)
    9 / 382 (2.36%)
    3 / 383 (0.78%)
         occurrences causally related to treatment / all
    0 / 6
    2 / 9
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HERNIA
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHILLS
         subjects affected / exposed
    0 / 375 (0.00%)
    2 / 382 (0.52%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DISEASE PROGRESSION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    FATIGUE
         subjects affected / exposed
    0 / 375 (0.00%)
    2 / 382 (0.52%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Immune system disorders
    ANAPHYLACTIC REACTION
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    1 / 375 (0.27%)
    2 / 382 (0.52%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    FEMALE GENITAL TRACT FISTULA
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VAGINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    PNEUMONITIS ASPIRATION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    4 / 375 (1.07%)
    0 / 382 (0.00%)
    7 / 383 (1.83%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMOPTYSIS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA AT REST
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COUGH
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ACUTE RESPIRATORY DISTRESS SYNDROME
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    PNEUMOTHORAX SPONTANEOUS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY THROMBOSIS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    10 / 375 (2.67%)
    12 / 382 (3.14%)
    10 / 383 (2.61%)
         occurrences causally related to treatment / all
    2 / 10
    3 / 13
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    RESPIRATORY TRACT CONGESTION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    SUICIDE ATTEMPT
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MENTAL STATUS CHANGES
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEPRESSION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONFUSIONAL STATE
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANXIETY
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    DEVICE BREAKAGE
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEVICE DISLOCATION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    INTERNATIONAL NORMALISED RATIO INCREASED
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SOLUBLE FIBRIN MONOMER COMPLEX INCREASED
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    ANASTOMOTIC LEAK
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ACETABULUM FRACTURE
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANKLE FRACTURE
         subjects affected / exposed
    2 / 375 (0.53%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONCUSSION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FALL
         subjects affected / exposed
    7 / 375 (1.87%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FRACTURED SACRUM
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL STOMA COMPLICATION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POST PROCEDURAL HAEMORRHAGE
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INCISIONAL HERNIA
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL ANASTOMOSIS COMPLICATION
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    JOINT DISLOCATION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUMBAR VERTEBRAL FRACTURE
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MULTIPLE INJURIES
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PELVIC FRACTURE
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEAT ILLNESS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROCEDURAL COMPLICATION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SKELETAL INJURY
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL COMPRESSION FRACTURE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SPINAL FRACTURE
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THORACIC VERTEBRAL FRACTURE
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VAGINAL CUFF DEHISCENCE
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND COMPLICATION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND DECOMPOSITION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND DEHISCENCE
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RIB FRACTURE
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE CORONARY SYNDROME
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    3 / 375 (0.80%)
    1 / 382 (0.26%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STRESS CARDIOMYOPATHY
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUPRAVENTRICULAR TACHYCARDIA
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TACHYCARDIA
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VENTRICULAR EXTRASYSTOLES
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PALPITATIONS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    MIGRAINE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOSS OF CONSCIOUSNESS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SYNCOPE
         subjects affected / exposed
    6 / 375 (1.60%)
    6 / 382 (1.57%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEURALGIA
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MIGRAINE WITH AURA
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBELLAR INFARCTION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL ARTERY EMBOLISM
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL VENOUS SINUS THROMBOSIS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEADACHE
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERSOMNIA
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    4 / 375 (1.07%)
    14 / 382 (3.66%)
    13 / 383 (3.39%)
         occurrences causally related to treatment / all
    3 / 4
    15 / 18
    10 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    APLASTIC ANAEMIA
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    6 / 375 (1.60%)
    12 / 382 (3.14%)
    16 / 383 (4.18%)
         occurrences causally related to treatment / all
    0 / 9
    10 / 16
    6 / 22
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    9 / 375 (2.40%)
    15 / 382 (3.93%)
    19 / 383 (4.96%)
         occurrences causally related to treatment / all
    2 / 10
    9 / 17
    9 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LEUKOPENIA
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BONE MARROW FAILURE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    3 / 375 (0.80%)
    10 / 382 (2.62%)
    9 / 383 (2.35%)
         occurrences causally related to treatment / all
    3 / 3
    14 / 20
    8 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    VISION BLURRED
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL ADHESIONS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL HERNIA
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL INCARCERATED HERNIA
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    5 / 375 (1.33%)
    9 / 382 (2.36%)
    9 / 383 (2.35%)
         occurrences causally related to treatment / all
    2 / 5
    1 / 10
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTEROCOLITIS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ASCITES
         subjects affected / exposed
    7 / 375 (1.87%)
    2 / 382 (0.52%)
    3 / 383 (0.78%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    3 / 383 (0.78%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLITIS ULCERATIVE
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONSTIPATION
         subjects affected / exposed
    3 / 375 (0.80%)
    2 / 382 (0.52%)
    5 / 383 (1.31%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    3 / 375 (0.80%)
    2 / 382 (0.52%)
    4 / 383 (1.04%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 2
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULAR PERFORATION
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EPIPLOIC APPENDAGITIS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MECHANICAL ILEUS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC VOLVULUS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMATEMESIS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMOPERITONEUM
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HIATUS HERNIA
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ILEAL PERFORATION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    ILEUS
         subjects affected / exposed
    2 / 375 (0.53%)
    3 / 382 (0.79%)
    7 / 383 (1.83%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    2 / 375 (0.53%)
    6 / 382 (1.57%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    INTESTINAL PERFORATION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL PSEUDO-OBSTRUCTION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTRA-ABDOMINAL FLUID COLLECTION
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE PERFORATION
         subjects affected / exposed
    2 / 375 (0.53%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC ULCER
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    4 / 375 (1.07%)
    13 / 382 (3.40%)
    11 / 383 (2.87%)
         occurrences causally related to treatment / all
    2 / 5
    14 / 16
    7 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGITIS ULCERATIVE
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS ACUTE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMOPERITONEUM
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    3 / 375 (0.80%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL PERFORATION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    SPIGELIAN HERNIA
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UPPER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    5 / 375 (1.33%)
    12 / 382 (3.14%)
    10 / 383 (2.61%)
         occurrences causally related to treatment / all
    3 / 5
    13 / 16
    6 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    19 / 375 (5.07%)
    11 / 382 (2.88%)
    13 / 383 (3.39%)
         occurrences causally related to treatment / all
    0 / 22
    0 / 14
    0 / 17
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLECYSTITIS
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHOLECYSTITIS ACUTE
         subjects affected / exposed
    0 / 375 (0.00%)
    2 / 382 (0.52%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BILE DUCT STONE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    SKIN ULCER
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    NEPHROLITHIASIS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URETEROLITHIASIS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYDRONEPHROSIS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY RETENTION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMATURIA
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    2 / 375 (0.53%)
    2 / 382 (0.52%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL VEIN THROMBOSIS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL INFARCT
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    ADRENAL INSUFFICIENCY
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTHYROIDISM
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    FLANK PAIN
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTERVERTEBRAL DISC PROTRUSION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUSCULAR WEAKNESS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOARTHRITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    ABDOMINAL ABSCESS
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    3 / 383 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATYPICAL MYCOBACTERIAL INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BACTERAEMIA
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BACTEROIDES BACTERAEMIA
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CATHETER SITE INFECTION
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    3 / 375 (0.80%)
    1 / 382 (0.26%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLONIC ABSCESS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CYSTITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EMPYEMA
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENDOCARDITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTEROBACTER INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTEROCOCCAL BACTERAEMIA
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTEROCOLITIS INFECTIOUS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ERYSIPELAS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ESCHERICHIA INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    0 / 375 (0.00%)
    3 / 382 (0.79%)
    3 / 383 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GROIN ABSCESS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HERPES ZOSTER
         subjects affected / exposed
    2 / 375 (0.53%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    IMPLANT SITE INFECTION
         subjects affected / exposed
    2 / 375 (0.53%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFECTED LYMPHOCELE
         subjects affected / exposed
    0 / 375 (0.00%)
    2 / 382 (0.52%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ESCHERICHIA URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTERVERTEBRAL DISCITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    KIDNEY INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LYMPHANGITIS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MENINGITIS CRYPTOCOCCAL
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PELVIC INFECTION
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NASOPHARYNGITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIC SEPSIS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OPHTHALMIC HERPES ZOSTER
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOMYELITIS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OTITIS MEDIA
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PELVIC ABSCESS
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NAIL INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    7 / 375 (1.87%)
    5 / 382 (1.31%)
    3 / 383 (0.78%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    SEPTIC EMBOLUS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIORBITAL CELLULITIS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERITONEAL ABSCESS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERITONITIS
         subjects affected / exposed
    2 / 375 (0.53%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PHARYNGITIS STREPTOCOCCAL
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    6 / 375 (1.60%)
    4 / 382 (1.05%)
    5 / 383 (1.31%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    2 / 375 (0.53%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POST PROCEDURAL INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POSTOPERATIVE ABSCESS
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POSTOPERATIVE WOUND INFECTION
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYELONEPHRITIS ACUTE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PHLEBITIS INFECTIVE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    5 / 375 (1.33%)
    4 / 382 (1.05%)
    3 / 383 (0.78%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
    1 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    1 / 1
    SPONTANEOUS BACTERIAL PERITONITIS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL INFECTION
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL SEPSIS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUBCUTANEOUS ABSCESS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUBDIAPHRAGMATIC ABSCESS
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    2 / 382 (0.52%)
    2 / 383 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    4 / 375 (1.07%)
    7 / 382 (1.83%)
    6 / 383 (1.57%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UROSEPSIS
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VIRAL INFECTION
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND INFECTION
         subjects affected / exposed
    2 / 375 (0.53%)
    0 / 382 (0.00%)
    3 / 383 (0.78%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SYSTEMIC CANDIDA
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    2 / 375 (0.53%)
    0 / 382 (0.00%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DIABETES MELLITUS
         subjects affected / exposed
    0 / 375 (0.00%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DECREASED APPETITE
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    6 / 375 (1.60%)
    6 / 382 (1.57%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    2 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERKALAEMIA
         subjects affected / exposed
    1 / 375 (0.27%)
    0 / 382 (0.00%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOALBUMINAEMIA
         subjects affected / exposed
    1 / 375 (0.27%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOCALCAEMIA
         subjects affected / exposed
    0 / 375 (0.00%)
    1 / 382 (0.26%)
    0 / 383 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOKALAEMIA
         subjects affected / exposed
    0 / 375 (0.00%)
    3 / 382 (0.79%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    2 / 375 (0.53%)
    6 / 382 (1.57%)
    1 / 383 (0.26%)
         occurrences causally related to treatment / all
    1 / 2
    4 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo + Carboplatin + Paclitaxel -> Placebo Veliparib + Carboplatin + Paclitaxel -> Veliparib Veliparib + Carboplatin + Paclitaxel -> Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    369 / 375 (98.40%)
    376 / 382 (98.43%)
    375 / 383 (97.91%)
    Vascular disorders
    HOT FLUSH
         subjects affected / exposed
    49 / 375 (13.07%)
    43 / 382 (11.26%)
    44 / 383 (11.49%)
         occurrences all number
    53
    50
    48
    HYPERTENSION
         subjects affected / exposed
    38 / 375 (10.13%)
    32 / 382 (8.38%)
    38 / 383 (9.92%)
         occurrences all number
    66
    60
    60
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    28 / 375 (7.47%)
    41 / 382 (10.73%)
    36 / 383 (9.40%)
         occurrences all number
    58
    64
    56
    FATIGUE
         subjects affected / exposed
    221 / 375 (58.93%)
    257 / 382 (67.28%)
    235 / 383 (61.36%)
         occurrences all number
    353
    456
    407
    MALAISE
         subjects affected / exposed
    21 / 375 (5.60%)
    31 / 382 (8.12%)
    22 / 383 (5.74%)
         occurrences all number
    34
    37
    31
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    19 / 375 (5.07%)
    18 / 382 (4.71%)
    16 / 383 (4.18%)
         occurrences all number
    21
    21
    18
    OEDEMA PERIPHERAL
         subjects affected / exposed
    73 / 375 (19.47%)
    56 / 382 (14.66%)
    58 / 383 (15.14%)
         occurrences all number
    84
    77
    62
    PAIN
         subjects affected / exposed
    22 / 375 (5.87%)
    21 / 382 (5.50%)
    22 / 383 (5.74%)
         occurrences all number
    25
    23
    31
    PYREXIA
         subjects affected / exposed
    25 / 375 (6.67%)
    23 / 382 (6.02%)
    33 / 383 (8.62%)
         occurrences all number
    28
    30
    38
    Immune system disorders
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    63 / 375 (16.80%)
    51 / 382 (13.35%)
    48 / 383 (12.53%)
         occurrences all number
    84
    56
    63
    Respiratory, thoracic and mediastinal disorders
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    39 / 375 (10.40%)
    27 / 382 (7.07%)
    24 / 383 (6.27%)
         occurrences all number
    46
    33
    27
    NASAL CONGESTION
         subjects affected / exposed
    26 / 375 (6.93%)
    18 / 382 (4.71%)
    6 / 383 (1.57%)
         occurrences all number
    29
    22
    6
    COUGH
         subjects affected / exposed
    58 / 375 (15.47%)
    59 / 382 (15.45%)
    57 / 383 (14.88%)
         occurrences all number
    70
    70
    63
    DYSPNOEA
         subjects affected / exposed
    76 / 375 (20.27%)
    84 / 382 (21.99%)
    91 / 383 (23.76%)
         occurrences all number
    106
    111
    112
    EPISTAXIS
         subjects affected / exposed
    59 / 375 (15.73%)
    56 / 382 (14.66%)
    61 / 383 (15.93%)
         occurrences all number
    70
    61
    66
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    58 / 375 (15.47%)
    59 / 382 (15.45%)
    61 / 383 (15.93%)
         occurrences all number
    72
    70
    74
    DEPRESSION
         subjects affected / exposed
    39 / 375 (10.40%)
    34 / 382 (8.90%)
    46 / 383 (12.01%)
         occurrences all number
    46
    43
    58
    INSOMNIA
         subjects affected / exposed
    89 / 375 (23.73%)
    109 / 382 (28.53%)
    120 / 383 (31.33%)
         occurrences all number
    105
    134
    141
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    41 / 375 (10.93%)
    40 / 382 (10.47%)
    31 / 383 (8.09%)
         occurrences all number
    64
    52
    55
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    31 / 375 (8.27%)
    31 / 382 (8.12%)
    22 / 383 (5.74%)
         occurrences all number
    46
    35
    41
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    19 / 375 (5.07%)
    16 / 382 (4.19%)
    10 / 383 (2.61%)
         occurrences all number
    26
    21
    13
    WEIGHT DECREASED
         subjects affected / exposed
    32 / 375 (8.53%)
    54 / 382 (14.14%)
    41 / 383 (10.70%)
         occurrences all number
    45
    71
    52
    WEIGHT INCREASED
         subjects affected / exposed
    35 / 375 (9.33%)
    36 / 382 (9.42%)
    26 / 383 (6.79%)
         occurrences all number
    49
    52
    34
    Injury, poisoning and procedural complications
    CONTUSION
         subjects affected / exposed
    13 / 375 (3.47%)
    20 / 382 (5.24%)
    17 / 383 (4.44%)
         occurrences all number
    13
    28
    21
    FALL
         subjects affected / exposed
    19 / 375 (5.07%)
    18 / 382 (4.71%)
    15 / 383 (3.92%)
         occurrences all number
    20
    23
    16
    PROCEDURAL PAIN
         subjects affected / exposed
    37 / 375 (9.87%)
    25 / 382 (6.54%)
    18 / 383 (4.70%)
         occurrences all number
    46
    25
    19
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    90 / 375 (24.00%)
    100 / 382 (26.18%)
    83 / 383 (21.67%)
         occurrences all number
    121
    126
    105
    DYSGEUSIA
         subjects affected / exposed
    57 / 375 (15.20%)
    73 / 382 (19.11%)
    47 / 383 (12.27%)
         occurrences all number
    70
    80
    54
    HEADACHE
         subjects affected / exposed
    97 / 375 (25.87%)
    98 / 382 (25.65%)
    90 / 383 (23.50%)
         occurrences all number
    136
    143
    124
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    256 / 375 (68.27%)
    242 / 382 (63.35%)
    235 / 383 (61.36%)
         occurrences all number
    415
    373
    346
    TREMOR
         subjects affected / exposed
    9 / 375 (2.40%)
    23 / 382 (6.02%)
    6 / 383 (1.57%)
         occurrences all number
    11
    26
    6
    Blood and lymphatic system disorders
    NEUTROPENIA
         subjects affected / exposed
    247 / 375 (65.87%)
    273 / 382 (71.47%)
    266 / 383 (69.45%)
         occurrences all number
    673
    848
    881
    LYMPHOPENIA
         subjects affected / exposed
    15 / 375 (4.00%)
    26 / 382 (6.81%)
    15 / 383 (3.92%)
         occurrences all number
    28
    57
    20
    LEUKOPENIA
         subjects affected / exposed
    89 / 375 (23.73%)
    114 / 382 (29.84%)
    87 / 383 (22.72%)
         occurrences all number
    223
    333
    261
    ANAEMIA
         subjects affected / exposed
    191 / 375 (50.93%)
    226 / 382 (59.16%)
    232 / 383 (60.57%)
         occurrences all number
    514
    672
    603
    THROMBOCYTOPENIA
         subjects affected / exposed
    119 / 375 (31.73%)
    209 / 382 (54.71%)
    216 / 383 (56.40%)
         occurrences all number
    266
    735
    630
    Eye disorders
    VISION BLURRED
         subjects affected / exposed
    32 / 375 (8.53%)
    27 / 382 (7.07%)
    19 / 383 (4.96%)
         occurrences all number
    33
    27
    22
    Gastrointestinal disorders
    DYSPEPSIA
         subjects affected / exposed
    41 / 375 (10.93%)
    36 / 382 (9.42%)
    45 / 383 (11.75%)
         occurrences all number
    53
    42
    55
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    22 / 375 (5.87%)
    34 / 382 (8.90%)
    28 / 383 (7.31%)
         occurrences all number
    23
    46
    30
    NAUSEA
         subjects affected / exposed
    246 / 375 (65.60%)
    289 / 382 (75.65%)
    259 / 383 (67.62%)
         occurrences all number
    425
    578
    433
    STOMATITIS
         subjects affected / exposed
    52 / 375 (13.87%)
    59 / 382 (15.45%)
    47 / 383 (12.27%)
         occurrences all number
    67
    67
    52
    VOMITING
         subjects affected / exposed
    128 / 375 (34.13%)
    174 / 382 (45.55%)
    123 / 383 (32.11%)
         occurrences all number
    211
    309
    170
    DIARRHOEA
         subjects affected / exposed
    149 / 375 (39.73%)
    164 / 382 (42.93%)
    137 / 383 (35.77%)
         occurrences all number
    248
    255
    228
    CONSTIPATION
         subjects affected / exposed
    157 / 375 (41.87%)
    165 / 382 (43.19%)
    177 / 383 (46.21%)
         occurrences all number
    203
    228
    241
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    29 / 375 (7.73%)
    29 / 382 (7.59%)
    18 / 383 (4.70%)
         occurrences all number
    38
    37
    24
    ABDOMINAL PAIN
         subjects affected / exposed
    114 / 375 (30.40%)
    118 / 382 (30.89%)
    105 / 383 (27.42%)
         occurrences all number
    163
    162
    143
    ABDOMINAL DISTENSION
         subjects affected / exposed
    45 / 375 (12.00%)
    34 / 382 (8.90%)
    48 / 383 (12.53%)
         occurrences all number
    55
    39
    54
    DRY MOUTH
         subjects affected / exposed
    19 / 375 (5.07%)
    22 / 382 (5.76%)
    10 / 383 (2.61%)
         occurrences all number
    20
    23
    12
    Skin and subcutaneous tissue disorders
    NAIL DISCOLOURATION
         subjects affected / exposed
    21 / 375 (5.60%)
    9 / 382 (2.36%)
    10 / 383 (2.61%)
         occurrences all number
    21
    9
    10
    ALOPECIA
         subjects affected / exposed
    214 / 375 (57.07%)
    197 / 382 (51.57%)
    216 / 383 (56.40%)
         occurrences all number
    271
    256
    271
    RASH MACULO-PAPULAR
         subjects affected / exposed
    30 / 375 (8.00%)
    22 / 382 (5.76%)
    11 / 383 (2.87%)
         occurrences all number
    35
    31
    15
    RASH
         subjects affected / exposed
    56 / 375 (14.93%)
    48 / 382 (12.57%)
    54 / 383 (14.10%)
         occurrences all number
    68
    53
    64
    PRURITUS
         subjects affected / exposed
    40 / 375 (10.67%)
    28 / 382 (7.33%)
    35 / 383 (9.14%)
         occurrences all number
    49
    33
    41
    Renal and urinary disorders
    DYSURIA
         subjects affected / exposed
    22 / 375 (5.87%)
    16 / 382 (4.19%)
    17 / 383 (4.44%)
         occurrences all number
    24
    17
    18
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    136 / 375 (36.27%)
    114 / 382 (29.84%)
    112 / 383 (29.24%)
         occurrences all number
    217
    166
    152
    BACK PAIN
         subjects affected / exposed
    66 / 375 (17.60%)
    67 / 382 (17.54%)
    66 / 383 (17.23%)
         occurrences all number
    87
    88
    75
    BONE PAIN
         subjects affected / exposed
    27 / 375 (7.20%)
    33 / 382 (8.64%)
    25 / 383 (6.53%)
         occurrences all number
    46
    37
    36
    MUSCULAR WEAKNESS
         subjects affected / exposed
    23 / 375 (6.13%)
    23 / 382 (6.02%)
    24 / 383 (6.27%)
         occurrences all number
    28
    33
    34
    MYALGIA
         subjects affected / exposed
    75 / 375 (20.00%)
    71 / 382 (18.59%)
    59 / 383 (15.40%)
         occurrences all number
    106
    96
    80
    PAIN IN EXTREMITY
         subjects affected / exposed
    55 / 375 (14.67%)
    51 / 382 (13.35%)
    46 / 383 (12.01%)
         occurrences all number
    70
    64
    56
    Infections and infestations
    NASOPHARYNGITIS
         subjects affected / exposed
    21 / 375 (5.60%)
    26 / 382 (6.81%)
    19 / 383 (4.96%)
         occurrences all number
    26
    32
    22
    SINUSITIS
         subjects affected / exposed
    18 / 375 (4.80%)
    21 / 382 (5.50%)
    18 / 383 (4.70%)
         occurrences all number
    27
    22
    20
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    43 / 375 (11.47%)
    34 / 382 (8.90%)
    28 / 383 (7.31%)
         occurrences all number
    52
    44
    36
    URINARY TRACT INFECTION
         subjects affected / exposed
    67 / 375 (17.87%)
    70 / 382 (18.32%)
    64 / 383 (16.71%)
         occurrences all number
    104
    91
    91
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    85 / 375 (22.67%)
    110 / 382 (28.80%)
    82 / 383 (21.41%)
         occurrences all number
    101
    143
    106
    DEHYDRATION
         subjects affected / exposed
    20 / 375 (5.33%)
    30 / 382 (7.85%)
    32 / 383 (8.36%)
         occurrences all number
    21
    37
    48
    HYPERGLYCAEMIA
         subjects affected / exposed
    18 / 375 (4.80%)
    27 / 382 (7.07%)
    18 / 383 (4.70%)
         occurrences all number
    35
    50
    26
    HYPOALBUMINAEMIA
         subjects affected / exposed
    19 / 375 (5.07%)
    16 / 382 (4.19%)
    12 / 383 (3.13%)
         occurrences all number
    31
    31
    17
    HYPOKALAEMIA
         subjects affected / exposed
    69 / 375 (18.40%)
    59 / 382 (15.45%)
    68 / 383 (17.75%)
         occurrences all number
    107
    94
    113
    HYPOMAGNESAEMIA
         subjects affected / exposed
    98 / 375 (26.13%)
    85 / 382 (22.25%)
    96 / 383 (25.07%)
         occurrences all number
    199
    143
    142
    HYPONATRAEMIA
         subjects affected / exposed
    25 / 375 (6.67%)
    25 / 382 (6.54%)
    21 / 383 (5.48%)
         occurrences all number
    33
    35
    24
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    21 / 375 (5.60%)
    11 / 382 (2.88%)
    14 / 383 (3.66%)
         occurrences all number
    31
    14
    18

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 May 2016
    Amendment 1 Modified the starting dose of maintenance therapy of veliparib/placebo to 300 mg BID and established process for site-level unblinding after disease progression.
    21 Sep 2016
    Amendment 2 Adjusted stratification factors to include gBRCA mutation status (positive vs. negative or Unknown) as per IDMC recommendation.
    14 Nov 2016
    Amendment 3 Clarified the use of growth factors and modified the neutrophil and PLT count threshold for starting cycles in maintenance phase.
    24 Mar 2017
    Amendment 4 Clarified dose modification guidance and provided guidance for starting and stopping veliparib/placebo for surgical procedures and management of subjects with IV contrast allergies.
    10 Dec 2018
    Amendment 5 Expanded planned analyses to investigate whether the addition of veliparib in combination with chemotherapy and in maintenance would improve outcomes in the HRD population.
    24 Apr 2019
    Amendment 6 Provided estimated number of events needed in treatment Arm 1 and Arm 3 to trigger the primary analyses of PFS in the BRCA-deficient, HRD, and whole populations.
    01 May 2020
    Amendment 7 Added benefits and risks evaluation information and updated study procedures in the context of the ongoing COVID-19 pandemic.
    08 Mar 2021
    Amendment 8 A final OS analyses occurred when required OS events accrued in all populations. Benefits and risks evaluation information added in the context of the ongoing COVID-19 pandemic.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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