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    Clinical Trial Results:
    A Randomized, Double-Blind, Phase 2, Dose-Ranging Study to Evaluate the Safety and Efficacy of Veliparib and Whole Brain Radiation Therapy Versus Placebo and Whole Brain Radiation Therapy in Subjects with Brain Metastases from Non-Small Cell Lung Cancer

    Summary
    EudraCT number
    		 2011-003618-18
    Trial protocol
    		 NO   BE   CZ   FI   ES   HU  
    Global end of trial date
    22 Jan 2015

    Results information
    Results version number
    		 v2(current)
    This version publication date
    09 Feb 2018
    First version publication date
    18 May 2016
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    2 corrections need to be made in the statistical analysis of 2 endpoints.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    M10-897
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01657799
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co. KG
    Sponsor organisation address
    Abbott House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6 4XE
    Public contact
    Global Medical Information, AbbVie, 001 800-633-9110,
    Scientific contact
    Vincent Giranda, MD, AbbVie, Vincent.Giranda@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
    22 Jan 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Jan 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess whether the addition of veliparib when given during whole brain radiation therapy (WBRT) improves overall survival (OS) for subjects with brain metastases from non-small cell lung cancer (NSCLC).
    Protection of trial subjects
    Subject, subject’s caregiver and/or or subject’s representative (if applicable) read and understood the information provided about the study and gave written permission.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Oct 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 48 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    Australia: 31
    Country: Number of subjects enrolled
    Canada: 28
    Country: Number of subjects enrolled
    Chile: 10
    Country: Number of subjects enrolled
    Egypt: 5
    Country: Number of subjects enrolled
    Korea, Republic of: 33
    Country: Number of subjects enrolled
    Russian Federation: 36
    Country: Number of subjects enrolled
    Taiwan: 30
    Country: Number of subjects enrolled
    Ukraine: 15
    Country: Number of subjects enrolled
    United States: 36
    Country: Number of subjects enrolled
    Norway: 8
    Country: Number of subjects enrolled
    Spain: 27
    Country: Number of subjects enrolled
    Belgium: 17
    Country: Number of subjects enrolled
    Czech Republic: 14
    Country: Number of subjects enrolled
    Finland: 5
    Country: Number of subjects enrolled
    France: 5
    Country: Number of subjects enrolled
    Hungary: 4
    Worldwide total number of subjects
    307
    EEA total number of subjects
    80
    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)
    205
    From 65 to 84 years
    100
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Subjects were randomized in a 1:1:1 ratio to 1 of 3 treatment groups. Randomization was stratified by graded prognostic assessment (GPA) score (≤ 2.5 versus > 2.5) and neurological symptoms (symptomatic versus asymptomatic). A total of 307 subjects were randomized; 1 subject did not receive study drug and was excluded from the safety analysis.

    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, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo BID plus WBRT
    Arm description
    		 Participants received placebo to veliparib twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.
    Arm type
    		 Placebo

    Investigational medicinal product name
    placebo for veliparib capsule
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    All subjects self-administered placebo for veliparib BID continuously throughout the entire course of WBRT, starting on Day 1 and including weekends or holidays when WBRT was not given, plus an additional day of dosing with placebo for veliparib BID the day following the last day of treatment with WBRT.

    Arm title
    		 Veliparib 50 mg BID plus WBRT
    Arm description
    		 Participants received veliparib 50 mg twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.
    Arm type
    		 Experimental

    Investigational medicinal product name
    veliparib 50 mg capsule
    Investigational medicinal product code
    Other name
    ABT-888
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    All subjects self-administered veliparib 50 mg BID continuously throughout the entire course of WBRT, starting on Day 1 and including weekends or holidays when WBRT was not given, plus an additional day of dosing with veliparib 50 mg BID the day following the last day of treatment with WBRT.

    Arm title
    		 Veliparib 200 mg BID plus WBRT
    Arm description
    		 Participants received veliparib 200 mg twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.
    Arm type
    		 Experimental

    Investigational medicinal product name
    veliparib 100 mg capsule
    Investigational medicinal product code
    Other name
    ABT-888
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    All subjects self-administered veliparib 200 mg BID continuously throughout the entire course of WBRT, starting on Day 1 and including weekends or holidays when WBRT was not given, plus an additional day of dosing with veliparib 200 mg BID the day following the last day of treatment with WBRT.

    Number of subjects in period 1
    		Placebo BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT
    Started
    102
    103
    102
    Received treatment
    101
    103
    102
    Completed
    0
    0
    0
    Not completed
    102
    103
    102
         Disease progression
    2
    4
    4
         Radiographic and clinical brain metastases
    16
    11
    15
         Adverse event related to progression
    6
    8
    12
         Not specified
    52
    62
    49
         Progressive disease clinical
    7
    4
    7
         Lost to follow-up
    1
    -
    1
         Withdrew consent
    13
    10
    10
         Adverse event not related to progression
    5
    4
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo BID plus WBRT
    Reporting group description
    		 Participants received placebo to veliparib twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.

    Reporting group title
    Veliparib 50 mg BID plus WBRT
    Reporting group description
    		 Participants received veliparib 50 mg twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.

    Reporting group title
    Veliparib 200 mg BID plus WBRT
    Reporting group description
    		 Participants received veliparib 200 mg twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.

    Reporting group values
    		 Placebo BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT Total
    Number of subjects
    		 102 103 102 307
    Age categorical
    Units: Subjects
        < 65 years
    		 68 73 64 205
        ≥ 65 years
    		 34 30 38 102
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60.0 ( 9.71 ) 59.8 ( 8.74 ) 61.8 ( 9.08 ) -
    Gender categorical
    Units: Subjects
        Female
    		 46 42 36 124
        Male
    		 56 61 66 183
    Race
    Units: Subjects
        White
    		 79 85 66 230
        Black
    		 0 2 6 8
        Asian
    		 22 16 28 66
        Natiave Hawaiian or Pacific Islander
    		 1 0 0 1
        Multirace
    		 0 0 2 2
    Graded Prognostic Assessment (GPA)
    A participant's GPA score was the sum total of each of the following prognostic factors, scored as 0, 0.5, or 1: • Age, years > 60 years, 50 - 59 years, or < 50 years) • Karnofsky Performance Status (< 70, 70 - 80, or 90 - 100) • No. of brain metastases (> 3, 2 - 3, or 1) • Extracranial metastases (present or absent) The total GPA score could range from 0 to 4 where lower scores indicate a worse prognosis.
    Units: Subjects
        ≤ 2.5
    		 91 91 92 274
        > 2.5
    		 11 12 10 33

    End points

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    End points reporting groups
    Reporting group title
    Placebo BID plus WBRT
    Reporting group description
    		 Participants received placebo to veliparib twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.

    Reporting group title
    Veliparib 50 mg BID plus WBRT
    Reporting group description
    		 Participants received veliparib 50 mg twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.

    Reporting group title
    Veliparib 200 mg BID plus WBRT
    Reporting group description
    		 Participants received veliparib 200 mg twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.

    Primary: Overall Survival: Percentage of Participants with an Event

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    End point title
    		 Overall Survival: Percentage of Participants with an Event [1]
    End point description
    Overall survival was defined as the number of days from the date of randomization to the date of the subject's death. All events of death were included, regardless of whether the event occurred while the subject was still taking study treatment or after the subject discontinued study treatment. If a subject had not died, the data were censored at the date the subject was last known to be alive.
    End point type
    Primary
    End point timeframe
    From randomization up to 36 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this end point per protocol.
    End point values
    		 Placebo BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT
    Number of subjects analysed
    102
    102
    102
    Units: percentage of subjects
        number (not applicable)
    73.5
    74.8
    71.6
    No statistical analyses for this end point

    Primary: Overall Survival: Time to Event

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    End point title
    		 Overall Survival: Time to Event
    End point description
    Overall survival was defined as the number of days from the date of randomization to the date of the subject's death. All events of death were included, regardless of whether the event occurred while the subject was still taking study treatment or after the subject discontinued study treatment. If a subject had not died, the data were censored at the date the subject was last known to be alive. Overall survival was estimated for each treatment group using Kaplan-Meier methodology.
    End point type
    Primary
    End point timeframe
    From randomization up to 36 months
    End point values
    		 Placebo BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT
    Number of subjects analysed
    102
    103
    102
    Units: days
        median (confidence interval 95%)
    185 (137 to 251)
    209 (169 to 264)
    209 (138 to 255)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The primary analysis used a Hochberg testing procedure to preserve the familywise error rate for multiple comparisons, where the larger P-value for the comparisons of veliparib 50 mg BID + WBRT with placebo BID + WBRT and veliparib 200 mg BID + WBRT with placebo BID + WBRT were compared to an α = 0.05. If statistically significant (P ≤ 0.05), both comparisons were considered significant. If the larger P-value was not statistically significant, the smaller P-value was compared to an α = 0.025.
    Comparison groups
    Placebo BID plus WBRT v Veliparib 50 mg BID plus WBRT
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.933 [2]
    Method
    		 Logrank
    Confidence interval
    Notes
    [2] - Log-rank test stratified by Graded Prognostic Assessment (GPA) score (≤2.5 or >2.5) at screening. Nominal P values were reported.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    The primary analysis used a Hochberg testing procedure to preserve the familywise error rate for multiple comparisons, where the larger P-value for the comparisons of veliparib 50 mg BID + WBRT with placebo BID + WBRT and veliparib 200 mg BID + WBRT with placebo BID + WBRT were compared to an α = 0.05. If statistically significant (P ≤ 0.05), both comparisons were considered significant. If the larger P-value was not statistically significant, the smaller P-value was compared to an α = 0.025.
    Comparison groups
    Placebo BID plus WBRT v Veliparib 50 mg BID plus WBRT
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.927 [3]
    Method
    		 Cox proportional hazard model
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.985
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.716
         upper limit
    		 1.355
    Notes
    [3] - Cox proportional hazard model stratified by GPA score (≤2.5 or >2.5) at screening. Nominal P values were reported.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    The primary analysis used a Hochberg testing procedure to preserve the familywise error rate for multiple comparisons, where the larger P-value for the comparisons of veliparib 50 mg BID + WBRT with placebo BID + WBRT and veliparib 200 mg BID + WBRT with placebo BID + WBRT were compared to an α = 0.05. If statistically significant (P ≤ 0.05), both comparisons were considered significant. If the larger P-value was not statistically significant, the smaller P-value was compared to an α = 0.025.
    Comparison groups
    Placebo BID plus WBRT v Veliparib 200 mg BID plus WBRT
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.909 [4]
    Method
    		 Logrank
    Confidence interval
    Notes
    [4] - Log-rank test stratified by GPA score (≤2.5 or >2.5) at screening. Nominal P values were reported.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    The primary analysis used a Hochberg testing procedure to preserve the familywise error rate for multiple comparisons, where the larger P-value for the comparisons of veliparib 50 mg BID + WBRT with placebo BID + WBRT and veliparib 200 mg BID + WBRT with placebo BID + WBRT were compared to an α = 0.05. If statistically significant (P ≤ 0.05), both comparisons were considered significant. If the larger P-value was not statistically significant, the smaller P-value was compared to an α = 0.025.
    Comparison groups
    Placebo BID plus WBRT v Veliparib 200 mg BID plus WBRT
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.906 [5]
    Method
    		 Cox proportional hazard model
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.981
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.354
    Notes
    [5] - Cox proportional hazard model stratified by GPA score (≤2.5 or >2.5) at screening. Nominal P values were reported.

    Secondary: Best Tumor Response Rate

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    End point title
    		 Best Tumor Response Rate
    End point description
    The best tumor response rate was calculated as the percentage of subjects with a complete response or partial response, as determined by brain scan imaging (magnetic resonance image [MRI]/ computed tomography [CT] scan) by a central imaging vendor.
    End point type
    Secondary
    End point timeframe
    From randomization up to 24 months
    End point values
    		 Placebo BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT
    Number of subjects analysed
    102
    103
    102
    Units: percentage of subjects
        number (confidence interval 95%)
    41.2 (31.5 to 51.4)
    36.9 (27.6 to 47)
    42.2 (32.4 to 52.3)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The P-value was calculated based on Cochran-Mantel-Haenszel (CMH) test stratified by GPA score (≤2.5 or >2.5) at screening.
    Comparison groups
    Placebo BID plus WBRT v Veliparib 50 mg BID plus WBRT
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.535
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    The P-value was calculated based on CMH test stratified by GPA score (≤2.5 or >2.5) at screening.
    Comparison groups
    Placebo BID plus WBRT v Veliparib 200 mg BID plus WBRT
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.898
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Intracranial Progression (Radiographic): Percentage of Participants with an Event

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    End point title
    		 Intracranial Progression (Radiographic): Percentage of Participants with an Event
    End point description
    Time to intracranial progression (radiographic) was defined as the number of days from the date of randomization to the date of the subject's first experience of intracranial progression, as determined by brain scan imaging (magnetic resonance image [MRI]/ computed tomography [CT] scan) by a central imaging vendor. All confirmed events of intracranial progression were included, regardless of whether the event occurred while the subject was still taking study treatment or had previously discontinued study treatment. If the subject did not have a confirmed event of intracranial progression, the subject's data were censored at the date of the subject's last available intracranial progression assessment.
    End point type
    Secondary
    End point timeframe
    From randomization up to 24 months
    End point values
    		 Placebo BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT
    Number of subjects analysed
    102
    103
    102
    Units: percentage of subjects
        number (not applicable)
    25.5
    34
    31.4
    No statistical analyses for this end point

    Secondary: Intracranial Progression (Radiographic): Time to Event

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    End point title
    		 Intracranial Progression (Radiographic): Time to Event
    End point description
    Time to intracranial progression (radiographic) was defined as the number of days from the date of randomization to the date of the subject's first experience of intracranial progression, as determined by brain scan imaging (magnetic resonance image [MRI]/ computed tomography [CT] scan) by a central imaging vendor. All confirmed events of intracranial progression were included, regardless of whether the event occurred while the subject was still taking study treatment or had previously discontinued study treatment. If the subject did not have a confirmed event of intracranial progression, the subject's data were censored at the date of the subject's last available intracranial progression assessment. Time to intracranial progression (radiographic) was estimated for each treatment group using Kaplan-Meier methodology. 9999 represents data not calculable.
    End point type
    Secondary
    End point timeframe
    From randomization up to 24 months
    End point values
    		 Placebo BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT
    Number of subjects analysed
    102
    103
    102
    Units: days
        median (confidence interval 95%)
    259 (184 to 9999)
    226 (147 to 360)
    224 (137 to 358)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo BID plus WBRT v Veliparib 50 mg BID plus WBRT
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.314 [6]
    Method
    		 Logrank
    Confidence interval
    Notes
    [6] - Log-rank test stratified by GPA score (≤ 2.5 or > 2.5) at screening.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo BID plus WBRT v Veliparib 50 mg BID plus WBRT
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.313 [7]
    Method
    		 Cox proportional hazard model
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.301
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 2.168
    Notes
    [7] - Cox proportional hazard model stratified by GPA score (≤ 2.5 or > 2.5) at screening.
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo BID plus WBRT v Veliparib 200 mg BID plus WBRT
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.536 [8]
    Method
    		 Logrank
    Confidence interval
    Notes
    [8] - Log-rank test stratified by GPA score (≤ 2.5 or > 2.5) at screening.
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    Placebo BID plus WBRT v Veliparib 200 mg BID plus WBRT
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.534 [9]
    Method
    		 Cox proportional hazard model
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.181
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.698
         upper limit
    		 1.999
    Notes
    [9] - Cox proportional hazard model stratified by GPA score (≤ 2.5 or > 2.5) at screening.

    Secondary: Clinical Brain Metastasis Progression: Percentage of Participants with an Event

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    End point title
    		 Clinical Brain Metastasis Progression: Percentage of Participants with an Event
    End point description
    Time to clinical brain metastases progression was defined as the number of days from randomization to the date of the subject's first experience of clinical brain metastases progression, as assessed by a team of neuro-oncology experts (Event Review Board). All events of clinical brain metastasis progression were included, regardless of whether the event occurred while the subject was still receiving study treatment or had previously discontinued study treatment. If a subject did not have an event of clinical brain metastases progression, the subject's data were censored at the date of the subject's last available clinical disease progression assessment.
    End point type
    Secondary
    End point timeframe
    From randomization up to 24 months
    End point values
    		 Placebo BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT
    Number of subjects analysed
    102
    103
    102
    Units: percentage of subjects
        number (not applicable)
    28.4
    74.8
    71.6
    No statistical analyses for this end point

    Secondary: Clinical Brain Metastasis Progression: Time to Event

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    End point title
    		 Clinical Brain Metastasis Progression: Time to Event
    End point description
    Time to clinical brain metastases progression was defined as the number of days from randomization to the date of the subject's first experience of clinical brain metastases progression, as assessed by a team of neuro-oncology experts (Event Review Board). All events of clinical brain metastasis progression were included, regardless of whether the event occurred while the subject was still receiving study treatment or had previously discontinued study treatment. If a subject did not have an event of clinical brain metastases progression, the subject's data were censored at the date of the subject's last available clinical disease progression assessment. Time to clinical brain metastasis progression was estimated for each treatment group using Kaplan-Meier methodology. 9999 represents data not calculable.
    End point type
    Secondary
    End point timeframe
    From randomization up to 24 months
    End point values
    		 Placebo BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT
    Number of subjects analysed
    102
    103
    102
    Units: days
        median (confidence interval 95%)
    348 (216 to 9999)
    286 (192 to 9999)
    255 (204 to 342)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The P-value was calculated based on Log-rank test stratified by GPA score (≤2.5 or >2.5) at screening.
    Comparison groups
    Placebo BID plus WBRT v Veliparib 50 mg BID plus WBRT
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.864
    Method
    		 Logrank
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    The P-value was calculated based on Cox proportional hazard model stratified by GPA score (≤2.5 or >2.5) at screening.
    Comparison groups
    Placebo BID plus WBRT v Veliparib 50 mg BID plus WBRT
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.86
    Method
    		 Cox proportional hazard model
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.047
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.626
         upper limit
    		 1.754
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    The P-value was calculated based on Log-rank test stratified by GPA score (≤2.5 or >2.5) at screening.
    Comparison groups
    Placebo BID plus WBRT v Veliparib 200 mg BID plus WBRT
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.301
    Method
    		 Logrank
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    The P-value was calculated based on Cox proportional hazard model stratified by GPA score (≤2.5 or >2.5) at screening.
    Comparison groups
    Veliparib 200 mg BID plus WBRT v Placebo BID plus WBRT
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.289
    Method
    		 Cox proportional hazard model
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.295
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.803
         upper limit
    		 2.086

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent adverse events (TEAEs) were collected from first dose of study drug until 30 days following last dose of study drug (up to 7 weeks).
    Adverse event reporting additional description
    Serious adverse events (SAEs) were collected after informed consent was obtained and before the first dose of study drug only if they were considered by the investigator to be causally related to study-required procedures (up to 11 weeks).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Placebo BID plus WBRT
    Reporting group description
    		 Placebo for veliparib twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.

    Reporting group title
    Veliparib 50 mg BID plus WBRT
    Reporting group description
    		 Veliparib 50 mg twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.

    Reporting group title
    Veliparib 200 mg BID plus WBRT
    Reporting group description
    		 Veliparib 200 mg twice daily (BID) during whole brain radiation therapy (WBRT). Treatment with WBRT began on Day 1. All subjects received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays. WBRT could be interrupted for up to a total of 7 days; however, no more than 4 consecutive days of interruption was permitted.

    Serious adverse events
    		 Placebo BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT
    Total subjects affected by serious adverse events
         subjects affected / exposed
    39 / 101 (38.61%)
    31 / 103 (30.10%)
    36 / 102 (35.29%)
         number of deaths (all causes)
    76
    83
    76
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Intracranial tumour haemorrhage
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Malignant neoplasm progression
         subjects affected / exposed
    8 / 101 (7.92%)
    10 / 103 (9.71%)
    16 / 102 (15.69%)
         occurrences causally related to treatment / all
    0 / 9
    2 / 11
    0 / 16
         deaths causally related to treatment / all
    0 / 7
    2 / 9
    0 / 13
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Thrombosis
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 101 (1.98%)
    0 / 103 (0.00%)
    0 / 102 (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
    General physical health deterioration
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Mucosal inflammation
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Pain
         subjects affected / exposed
    3 / 101 (2.97%)
    0 / 103 (0.00%)
    0 / 102 (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
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Interstitial lung disease
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 103 (0.97%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Pulmonary artery thrombosis
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    1 / 101 (0.99%)
    3 / 103 (2.91%)
    2 / 102 (1.96%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Respiratory failure
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Lower limb fracture
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Bradycardia
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Pericardial effusion
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Nervous system disorders
    Altered state of consciousness
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    4 / 101 (3.96%)
    0 / 103 (0.00%)
    0 / 102 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Convulsion
         subjects affected / exposed
    3 / 101 (2.97%)
    0 / 103 (0.00%)
    2 / 102 (1.96%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Haemorrhagic stroke
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Hemiplegia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Ischaemic stroke
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Nerve compression
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Status epilepticus
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Vasogenic cerebral oedema
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Thrombocytopenia
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    2 / 102 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Constipation
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Dyspepsia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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 perforation
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Nausea
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Proctalgia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Vomiting
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    2 / 102 (1.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Infections and infestations
    Bacterial infection
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Lung infection
         subjects affected / exposed
    2 / 101 (1.98%)
    1 / 103 (0.97%)
    0 / 102 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Nosocomial infection
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Oral candidiasis
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    Oral fungal infection
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    8 / 101 (7.92%)
    3 / 103 (2.91%)
    3 / 102 (2.94%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    Pneumonia streptococcal
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 103 (0.97%)
    0 / 102 (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
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Sinusitis
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    0 / 102 (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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 103 (0.00%)
    1 / 102 (0.98%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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 BID plus WBRT Veliparib 50 mg BID plus WBRT Veliparib 200 mg BID plus WBRT
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    78 / 101 (77.23%)
    76 / 103 (73.79%)
    77 / 102 (75.49%)
    Injury, poisoning and procedural complications
    Radiation skin injury
         subjects affected / exposed
    5 / 101 (4.95%)
    5 / 103 (4.85%)
    6 / 102 (5.88%)
         occurrences all number
    5
    5
    6
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    11 / 101 (10.89%)
    8 / 103 (7.77%)
    10 / 102 (9.80%)
         occurrences all number
    11
    8
    11
    Dysgeusia
         subjects affected / exposed
    7 / 101 (6.93%)
    4 / 103 (3.88%)
    2 / 102 (1.96%)
         occurrences all number
    7
    4
    2
    Headache
         subjects affected / exposed
    15 / 101 (14.85%)
    18 / 103 (17.48%)
    21 / 102 (20.59%)
         occurrences all number
    20
    21
    22
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    2 / 101 (1.98%)
    4 / 103 (3.88%)
    6 / 102 (5.88%)
         occurrences all number
    2
    4
    8
    Constipation
         subjects affected / exposed
    11 / 101 (10.89%)
    10 / 103 (9.71%)
    11 / 102 (10.78%)
         occurrences all number
    11
    10
    11
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    11 / 101 (10.89%)
    9 / 103 (8.74%)
    13 / 102 (12.75%)
         occurrences all number
    13
    9
    16
    Fatigue
         subjects affected / exposed
    20 / 101 (19.80%)
    27 / 103 (26.21%)
    21 / 102 (20.59%)
         occurrences all number
    23
    30
    25
    Pyrexia
         subjects affected / exposed
    7 / 101 (6.93%)
    7 / 103 (6.80%)
    4 / 102 (3.92%)
         occurrences all number
    9
    8
    4
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    8 / 101 (7.92%)
    8 / 103 (7.77%)
    7 / 102 (6.86%)
         occurrences all number
    9
    9
    7
    Nausea
         subjects affected / exposed
    29 / 101 (28.71%)
    23 / 103 (22.33%)
    32 / 102 (31.37%)
         occurrences all number
    30
    25
    35
    Vomiting
         subjects affected / exposed
    14 / 101 (13.86%)
    5 / 103 (4.85%)
    9 / 102 (8.82%)
         occurrences all number
    17
    5
    11
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 101 (5.94%)
    6 / 103 (5.83%)
    2 / 102 (1.96%)
         occurrences all number
    6
    6
    2
    Dyspnoea
         subjects affected / exposed
    14 / 101 (13.86%)
    7 / 103 (6.80%)
    10 / 102 (9.80%)
         occurrences all number
    19
    7
    10
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    19 / 101 (18.81%)
    15 / 103 (14.56%)
    15 / 102 (14.71%)
         occurrences all number
    19
    15
    15
    Rash
         subjects affected / exposed
    2 / 101 (1.98%)
    6 / 103 (5.83%)
    7 / 102 (6.86%)
         occurrences all number
    2
    6
    7
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    8 / 101 (7.92%)
    6 / 103 (5.83%)
    2 / 102 (1.96%)
         occurrences all number
    8
    6
    2
    Insomnia
         subjects affected / exposed
    11 / 101 (10.89%)
    10 / 103 (9.71%)
    6 / 102 (5.88%)
         occurrences all number
    11
    10
    6
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    6 / 101 (5.94%)
    7 / 103 (6.80%)
    4 / 102 (3.92%)
         occurrences all number
    6
    7
    4
    Infections and infestations
    Oral candidiasis
         subjects affected / exposed
    7 / 101 (6.93%)
    3 / 103 (2.91%)
    5 / 102 (4.90%)
         occurrences all number
    7
    3
    5
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    14 / 101 (13.86%)
    11 / 103 (10.68%)
    15 / 102 (14.71%)
         occurrences all number
    16
    12
    16

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Mar 2013
    The primary purpose of this amendment was to allow for broader eligibility while maintaining subject characteristics consistent with the trial intent (e.g., subjects with diagnosed brain metastases from NSCLC who were eligible for WBRT). The changes included inclusion (CT scan of brain with or without contrast could be obtained is subject was medically ineligible for MRI) and exclusion criteria (subjects could begin treatment within 28 days instead of 21 days; removed requirement for GPA score ≤1 since the subject population was > 60 years, had multiple brain metastases, and had presence of NSCLC outside the brain); clarified procedures and timing; and increased the number of sites from 100 to 120.
    08 Oct 2014
    The study was terminated by AbbVie prior to any sites executing the study under Amendment No. 2. The primary purpose of this amendment was to include additional neurological assessments beyond the Month 24 Visit (up to Month 48) at the request of the European Medicines Agency in order to analyze if veliparib may have any long-term effect on a subject's neurological function.

    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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