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    Clinical Trial Results:
    A Randomized, Phase III, Open-Label Study of Oral Topotecan Plus Whole-Brain Radiation Therapy (WBRT) Compared with WBRT Alone in Patients with Brain Metastases from Non-Small Cell Lung Cancer.

    Summary
    EudraCT number
    2006-002074-22
    Trial protocol
    HU   SK  
    Global end of trial date
    16 Aug 2013

    Results information
    Results version number
    v1(current)
    This version publication date
    02 May 2016
    First version publication date
    26 Apr 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    UM2005/00201/00
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    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
    16 Aug 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Aug 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to evaluate the efficacy of treatment with either oral topotecan plus WBRT or WBRT alone in patients with brain metastases due to NSCLC.
    Protection of trial subjects
    Not applicable
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    06 Dec 2006
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 45
    Country: Number of subjects enrolled
    Poland: 111
    Country: Number of subjects enrolled
    Russian Federation: 90
    Country: Number of subjects enrolled
    United States: 45
    Country: Number of subjects enrolled
    Hungary: 173
    Country: Number of subjects enrolled
    Slovakia: 8
    Worldwide total number of subjects
    472
    EEA total number of subjects
    292
    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)
    358
    From 65 to 84 years
    114
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Participants (par.) were randomly assigned to receive either topotecan capsules 1.1 mg/m2/day plus WBRT 3 Gy/day (experimental/chemoradiation arm) or WBRT alone 3 Gy/day over ten days. The randomization was stratified by the number of brain lesions and RPA Class.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Chemoradiation: Topotecan plus WBRT
    Arm description
    Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
    Arm type
    Experimental

    Investigational medicinal product name
    Topotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1.1 mg/m2/day

    Investigational medicinal product name
    whole-brain radiation therapy (WBRT)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Kit for radiopharmaceutical preparation
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    3 Gy/day

    Arm title
    Radiation: WBRT Alone
    Arm description
    Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
    Arm type
    Active comparator

    Investigational medicinal product name
    whole-brain radiation therapy (WBRT)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Kit for radiopharmaceutical preparation
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    3 Gy/day

    Number of subjects in period 1
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Started
    236
    236
    Completed
    206
    204
    Not completed
    30
    32
         Death
    1
    -
         Protocol deviation
    2
    2
         Physician decision
    -
    1
         Investigator Decision
    4
    6
         Consent withdrawn by subject
    12
    15
         Ongoing
    4
    2
         Lost to follow-up
    7
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Chemoradiation: Topotecan plus WBRT
    Reporting group description
    Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.

    Reporting group title
    Radiation: WBRT Alone
    Reporting group description
    Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.

    Reporting group values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone Total
    Number of subjects
    236 236 472
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    59.4 ± 8.56 57.8 ± 8.65 -
    Gender categorical
    Units: Subjects
        Female
    84 78 162
        Male
    152 158 310
    Race
    Units: Subjects
        African American/African Heritage (Her.)
    3 1 4
        Central/South Asian Heritage
    1 0 1
        Japanese/East Asian Heritage/South East Asian Her.
    0 3 3
        Native Hawaiian or other Pacific Islander
    1 0 1
        White
    230 232 462
        Asian & White
    1 0 1
    Race
    Units: Subjects
        African American/African Heritage (Her.)
    3 1 4
        Central/South Asian Heritage
    1 0 1
        Japanese/East Asian Heritage/South East Asian Her.
    0 3 3
        Native Hawaiian or other Pacific Islander
    1 0 1
        White
    230 232 462
        Asian & White
    1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Chemoradiation: Topotecan plus WBRT
    Reporting group description
    Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.

    Reporting group title
    Radiation: WBRT Alone
    Reporting group description
    Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.

    Primary: Overall Survival

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    End point title
    Overall Survival
    End point description
    Overall survival is defined as the time from randomization until the date of death due to any cause. The date of last contact was used for those participants who had not died or were lost to follow-up. These participants were classified as having been censored. Intent-to-Treat (ITT) Population: all randomized participants. Participants were analyzed by the treatment to which they were randomized, even if this differed from the treatment they actually received.
    End point type
    Primary
    End point timeframe
    From the time of Randomization until the date of death due to any cause (up to 195 weeks)
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    236 [1]
    236 [2]
    Units: months
        median (confidence interval 95%)
    4 (3.4 to 4.8)
    3.6 (3 to 4)
    Notes
    [1] - ITT Population
    [2] - ITT Population
    Statistical analysis title
    Anaysis 1
    Comparison groups
    Chemoradiation: Topotecan plus WBRT v Radiation: WBRT Alone
    Number of subjects included in analysis
    472
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    = 0.1862 [4]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.73
         upper limit
    1.07
    Notes
    [3] - The hazard ratio is estimated using a Pike estimator. The hazard ratio from a stratified log-rank test is adjusted for RPA class and the number of brain lesions at Screening.
    [4] - p-value from a stratified log-rank test is adjusted for Recursive Partitioning Analysis (RPA) class and the number of brain lesions at Screening.

    Secondary: Six-month survival

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    End point title
    Six-month survival
    End point description
    Six-month survival is defined as the percentage of participants alive at 6 months following randomization. The date of last contact was used for those participants who had not died or were lost to follow-up. These participants were classified as having been censored.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    236 [5]
    236 [6]
    Units: percentage of participants
    36
    28
    Notes
    [5] - ITT Population
    [6] - ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with a complete response (CR) or a partial response (PR) (central nervous system [CNS]-radiologic)

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    End point title
    Number of participants with a complete response (CR) or a partial response (PR) (central nervous system [CNS]-radiologic)
    End point description
    The number of participants achieving either a CR or PR, per World Health Organization (WHO) Criteria, in the CNS was assessed. CR is defined as the complete disappearance of all known measurable (Must be accurately measured in >=1 dimension) and nonmeasurable disease, without clinical, laboratory, or radiological evidence of recurrence for at least 4 weeks. CR may have been defined in participants with measurable and/or non-measurable disease at Screening. PR is defined as at least a 50% decrease in the sum of the products of the greatest length and perpendicular width of all measurable disease with no clear increase in nonmeasurable disease in participants without measurable disease. In both cases, there must have been no appearance of new disease, and no clinical, laboratory, or radiological evidence of disease progression for at least 4 weeks. Assessment of response was performed by the investigator and was based on unconfirmed responses.
    End point type
    Secondary
    End point timeframe
    From the time of Randomization until the time of CR or PR (up to 75 weeks)
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    236 [7]
    236 [8]
    Units: participants
        Complete response
    23
    11
        Partial response
    63
    61
    Notes
    [7] - ITT Population
    [8] - ITT Population
    No statistical analyses for this end point

    Secondary: Time to response (TTR) (CNS-radiologic)

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    End point title
    Time to response (TTR) (CNS-radiologic)
    End point description
    TTR is defined as the time from Randomization until the first documented evidence of CR or PR in the CNS. CR is defined as the complete disappearance of all known measurable (Must be accurately measured in >=1 dimension) and nonmeasurable disease, without clinical, laboratory, or radiological evidence of recurrence for at least 4 weeks. CR may have been defined in participants with measurable and/or non-measurable disease at Screening. PR is defined as at least a 50% decrease in the sum of the products of the greatest length and perpendicular width of all measurable disease with no clear increase in nonmeasurable disease in participants without measurable disease. In both cases, there must have been no appearance of new disease, and no clinical, laboratory, or radiological evidence of disease progression for at least 4 weeks. Assessment of response was performed by the investigator and was based on unconfirmed responses.
    End point type
    Secondary
    End point timeframe
    From the time of Randomization until the first documented evidence of CR or PR (up to 75 weeks)
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    173 [9]
    170 [10]
    Units: weeks
        median (confidence interval 95%)
    8 (7.7 to 8.1)
    8.1 (6 to 8.1)
    Notes
    [9] - ITT Population. Only those participants with a CR, PR, or a missing response were assessed.
    [10] - ITT Population. Only those participants with a CR, PR, or a missing response were assessed.
    No statistical analyses for this end point

    Secondary: Time to progression (TTP) (CNS-radiologic)

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    End point title
    Time to progression (TTP) (CNS-radiologic)
    End point description
    TTP is defined as the time from Randomization until the first documented sign of disease progression in the CNS. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. TTP was analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before a TTP event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.
    End point type
    Secondary
    End point timeframe
    From the time of Randomization until the first documented sign of disease progression (up to 75 weeks)
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    236 [11]
    236 [12]
    Units: weeks
        median (confidence interval 95%)
    9.7 (8.1 to 13.9)
    9.7 (8.3 to 10.9)
    Notes
    [11] - ITT Population
    [12] - ITT Population
    No statistical analyses for this end point

    Secondary: Time to progression (TTP) (all sites of disease-radiologic)

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    End point title
    Time to progression (TTP) (all sites of disease-radiologic)
    End point description
    TTP is defined as the time from Randomization until the first documented sign of disease progression in all sites of disease. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. TTP was analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before a TTP event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.
    End point type
    Secondary
    End point timeframe
    From the time of Randomization until the first documented sign of disease progression (up to 75 weeks)
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    236 [13]
    236 [14]
    Units: weeks
        median (confidence interval 95%)
    8 (6.7 to 8.7)
    7.7 (6.1 to 8.1)
    Notes
    [13] - ITT Population
    [14] - ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants who ranked each individual indicated neurological sign and symptom as none, mild, moderate, or severe at Months 1 and 3

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    End point title
    Number of participants who ranked each individual indicated neurological sign and symptom as none, mild, moderate, or severe at Months 1 and 3
    End point description
    Neurological signs and symptoms data were derived from a participant-reported diary. The participants were asked to assess the following signs and symptoms on a scale of none, mild, moderate, or severe at Months 1 and 3: headache, problems with balance/coordination (PB/C), leg weakness, arm weakness, loss of feeling/numbness (LofF/N), speech difficulty (SD), confusion, loss of memory (LofM), drowsiness, nausea, vomiting, dizziness, visual problems (VP), seizures, leg/ankle swelling (L/AS), heart burn, difficulty sleeping (DS), tiredness, and appetite/weight gain (A/WG). Only those participants who were assessed for the indicated sign and symptom at the indicated time point were analyzed.
    End point type
    Secondary
    End point timeframe
    Months 1 and 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    179 [15]
    189 [16]
    Units: participants
        Headache, Month 1, none, n=179, 189
    93
    106
        Headache, Month 1, mild, n=179, 189
    71
    68
        Headache, Month 1, moderate, 179, 189
    11
    13
        Headache, Month 1, severe, 179, 189
    4
    2
        Headache, Month 3, none, n=109, 111
    69
    53
        Headache, Month 3, mild, n=109, 111
    33
    41
        Headache, Month 3, moderate, n=109, 111
    5
    14
        Headache, Month 3, severe, n=109, 111
    2
    3
        PB/C, Month 1, none, n=179, 188
    84
    79
        PB/C, Month 1, mild, n=179, 188
    66
    71
        PB/C, Month 1, moderate, n=179, 188
    22
    30
        PB/C, Month 1, severe, n=179, 188
    7
    8
        PB/C, Month 3, none, n=109, 111
    69
    46
        PB/C, Month 3, mild, n=109, 111
    28
    36
        PB/C, Month 3, moderate, n=109, 111
    10
    18
        PB/C, Month 3, severe, n=109, 111
    2
    11
        Leg weakness, Month 1, none, n=179, 188
    47
    59
        Leg weakness, Month 1, mild, n=179, 188
    73
    72
        Leg weakness, Month 1, moderate, n=179, 188
    41
    41
        Leg weakness, Month 1, severe, n=179, 188
    18
    16
        Leg weakness, Month 3, none, n=109, 111
    28
    34
        Leg weakness, Month 3, mild, n=109, 111
    51
    37
        Leg weakness, Month 3, moderate, n=109, 111
    20
    19
        Leg weakness, Month 3, severe, n=109, 111
    10
    21
        Arm weakness, Month 1, none, n=179, 188
    96
    97
        Arm weakness, Month 1, mild, n=179, 188
    55
    60
        Arm weakness, Month 1, moderate, n=179, 188
    23
    18
        Arm weakness, Month 1, severe, n=179, 188
    5
    13
        Arm weakness, Month 3, none, n=109, 111
    60
    53
        Arm weakness, Month 3, mild, n=109, 111
    39
    34
        Arm weakness, Month 3, molderate, n=109, 111
    8
    16
        Arm weakness, Month 3, severe, n=109, 111
    2
    8
        LofF/N, Month 1, none, n=179, 188
    101
    111
        LofF/N, Month 1, mild, n=179, 188
    53
    43
        LofF/N, Month 1, moderate, n=179, 188
    17
    25
        LofF/N, Month 1, severe, n=179, 188
    8
    9
        LofF/N, Month 3, none, n=109, 111
    73
    66
        LofF/N, Month 3, mild, n=109, 111
    28
    27
        LofF/N, Month 3, moderate, n=109, 111
    3
    11
        LofF/N, Month 3, severe, n=109, 111
    5
    7
        SD, Month 1, none, n=179, 188
    151
    137
        SD, Month 1, mild, n=179, 188
    16
    40
        SD, Month 1, moderate, n=179, 188
    9
    9
        SD, Month 1, severe, n=179, 188
    3
    2
        SD, Month 3, none, n=109, 110
    94
    78
        SD, Month 3, mild, n=109, 110
    11
    22
        SD, Month 3, moderate, n=109, 110
    2
    8
        SD, Month 3, severe, n=109, 110
    2
    2
        Confusion, Month 1, none, n=179, 188
    150
    148
        Confusion, Month 1, mild, n=179, 188
    20
    32
        Confusion, Month 1, moderate, n=179, 188
    6
    7
        Confusion, Month 1, severe, n=179, 188
    3
    1
        Confusion, Month 3, none, n=109, 110
    99
    71
        Confusion, Month 3, mild, n=109, 110
    7
    29
        Confusion, Month 3, moderate, n=109, 110
    2
    9
        Confusion, Month 3, severe, n=109, 110
    1
    1
        LofM, Month 1, none, n=179, 188
    149
    141
        LofM, Month 1, mild, n=179, 188
    20
    41
        LofM, Month 1, moderate, n=179, 188
    8
    5
        LofM, Month 1, severe, n=179, 188
    2
    1
        LofM, Month 3, none, n=109, 110
    93
    78
        LofM, Month 3, mild, n=109, 110
    14
    25
        LofM, Month 3, moderate, n=109, 110
    1
    6
        LofM, Month 3, severe, n=109, 110
    1
    1
        Drowsiness, Month 1, none, n=179, 188
    90
    96
        Drowsiness, Month 1, mild, n=179, 188
    55
    59
        Drowsiness, Month 1, moderate, n=179, 188
    25
    26
        Drowsiness, Month 1, severe, n=179, 188
    9
    7
        Drowsiness, Month 3, none, n=109, 111
    50
    44
        Drowsiness, Month 3, mild, n=109, 111
    42
    40
        Drowsiness, Month 3, moderate, n=109, 111
    15
    15
        Drowsiness, Month 3, severe, n=109, 111
    2
    12
        Nausea, Month 1, none, n=179, 188
    125
    142
        Nausea, Month 1, mild, n=179, 188
    38
    36
        Nausea, Month 1, moderate, n=179, 188
    12
    10
        Nausea, Month 1, severe, n=179, 188
    4
    0
        Nausea, Month 3, none, n=109, 111
    70
    73
        Nausea, Month 3, mild, n=109, 111
    31
    29
        Nausea, Month 3, moderate, n=109, 111
    7
    6
        Nausea, Month 3, severe, n=109, 111
    1
    3
        Vomiting, Month 1, none, n=179, 188
    153
    164
        Vomiting, Month 1, mild, n=179, 188
    20
    19
        Vomiting, Month 1, moderate, n=179, 188
    4
    4
        Vomiting, Month 1, severe, n=179, 188
    2
    1
        Vomiting, Month 3, none, n=109, 111
    89
    91
        Vomiting, Month 3, mild, n=109, 111
    15
    15
        Vomiting, Month 3, moderate, n=109, 111
    4
    3
        Vomiting, Month 3, severe=109, 111
    1
    2
        Dizziness, Month 1, none, n=179, 188
    96
    94
        Dizziness, Month 1, mild, n=179, 188
    58
    70
        Dizziness, Month 1, moderate, n=179, 188
    22
    21
        Dizziness, Month 1, severe, n=179, 188
    3
    3
        Dizziness, Month 3, none, n=109, 111
    64
    54
        Dizziness, Month 3, mild, n=109, 111
    35
    36
        Dizziness, Month 3, moderate, n=109, 111
    7
    14
        Dizziness, Month 3, severe, n=109, 111
    3
    7
        VP, Month 1, none, n=179, 188
    103
    117
        VP, Month 1, mild, n=179, 188
    54
    53
        VP, Month 1, moderate, n=179, 188
    17
    16
        VP, Month 1, severe, n=179, 188
    5
    2
        VP, Month 3, none, n=109, 111
    72
    69
        VP, Month 3, mild, n=109, 111
    29
    28
        VP, Month 3, moderate, n=109, 111
    7
    10
        VP, Month 3, severe, n=109, 111
    1
    4
        Seizures, Month 1, none, n=179, 188
    173
    179
        Seizures, Month 1, mild, n=179, 188
    5
    7
        Seizures, Month 1, moderate, n=179, 188
    1
    2
        Seizures, Month 1, severe, n=179, 188
    0
    0
        Seizures, Month 3, none, n=109, 110
    108
    102
        Seizures, Month 3, mild, n=109, 110
    0
    4
        Seizures, Month 3, moderate, n=109, 110
    1
    3
        Seizures, Month 3, severe, n=109, 110
    0
    1
        L/AS, Month 1, none, n=179, 188
    141
    138
        L/AS, Month 1, mild, n=179, 188
    21
    29
        L/AS, Month 1, moderate, n=179, 188
    12
    15
        L/AS, Month 1, severe, n=179, 188
    5
    6
        L/AS, Month 3, none, n=109, 111
    86
    85
        L/AS, Month 3, mild, n=109, 111
    19
    19
        L/AS, Month 3, moderate, n=109, 111
    3
    6
        L/AS, Month 3, severe, n=109, 111
    1
    1
        Heartburn, Month 1, none, n=179, 188
    142
    151
        Heartburn, Month 1, mild, n=179, 188
    26
    27
        Heartburn, Month 1, moderate, n=179, 188
    9
    9
        Heartburn, Month 1, severe, n=179, 188
    2
    1
        Heartburn, Month 3, none, n=109, 111
    87
    86
        Heartburn, Month 3, mild, n=109, 111
    16
    18
        Heartburn, Month 3, moderate, n=109, 111
    4
    6
        Heartburn, Month 3, severe, n=109, 111
    2
    1
        DS, Month 1, none, n=179, 188
    112
    109
        DS, Month 1, mild, n=179, 188
    41
    48
        DS, Month 1, moderate, n=179, 188
    15
    24
        DS, Month 1, severe, n=179, 188
    11
    7
        DS, Month 3, none, n=109, 110
    78
    71
        DS, Month 3, mild, n=109, 110
    20
    23
        DS, Month 3, moderate, n=109, 110
    8
    12
        DS, Month 3, severe, n=109, 110
    3
    4
        Tiredness, Month 1, none, n=179, 188
    42
    42
        Tiredness, Month 1, mild, n=179, 188
    75
    85
        Tiredness, Month 1, moderate, n=179, 188
    46
    44
        Tiredness, Month 1, severe, n=179, 188
    16
    17
        Tiredness, Month 3, none, n=109, 111
    28
    21
        Tiredness, Month 3, mild, n=109, 111
    52
    42
        Tiredness, Month 3, moderate, n=109, 111
    19
    32
        Tiredness, Month 3, severe, n=109, 111
    10
    16
        A/WG, Month 1, none, n=179, 188
    107
    113
        A/WG, Month 1, mild, n=179, 188
    42
    41
        A/WG, Month 1, moderate, n=179, 188
    19
    29
        A/WG, Month 1, severe, n=179, 188
    11
    5
        A/WG, Month 3, none, n=108, 111
    71
    73
        A/WG, Month 3, mild, n=108, 111
    27
    23
        A/WG, Month 3, moderate, n=108, 111
    4
    11
        A/WG, Month 3, severe, n=108, 111
    6
    4
    Notes
    [15] - ITT Population
    [16] - ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment for the neurological sign and symptom of level of consciousness at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment for the neurological sign and symptom of level of consciousness at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants for the neurological sign and symptom of level of consciousness and assigned each participant to one of the following categories: normal; somnolence or sedation not interfering with function (not intefering); somnolence or sedation interfering with function, but not activities of daily living (ADLs) (interfering); obtundation or stupor, difficult to arouse, inteferring with ADLs (obtundation or stupor); coma. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [17]
    228 [18]
    Units: participants
        Baseline, normal, n=230, 228
    219
    216
        Month 1, normal, n=178, 180
    171
    169
        Month 3, normal, n=109, 107
    102
    92
        Baseline, not interfering, n=230, 228
    7
    9
        Month 1, not interfering, n=178, 180
    5
    7
        Month 3, not interfering, n=109, 107
    3
    8
        Baseline, interfering, n=230, 228
    3
    3
        Month 1, interfering, n=178, 180
    0
    4
        Month 3, interfering, n=109, 107
    3
    5
        Baseline, obtundation and stupor, n=230, 228
    1
    0
        Month 1, obtundation and stupor, n=178, 180
    2
    0
        Month 3, obtundation and stupor, n=109, 107
    1
    2
    Notes
    [17] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [18] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment for the neurological sign and symptom of headache at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment for the neurological sign and symptom of headache at Baseline, Month 1, and Month 3
    End point description
    The investigator (per Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) assessed par. for headache and assigned each par. to one of the following categories:absent, Grade (G) 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE. If no data are presented for a particular grade and time point, then no par. had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [19]
    228 [20]
    Units: participants
        Baseline, absent, n=230, 228
    141
    146
        Month 1, absent, n=178, 180
    126
    127
        Month 3, absent, n=109, 107
    85
    74
        Baseline, Grade 1, n=230, 228
    62
    55
        Month 1, Grade 1, n=178, 180
    43
    38
        Month 3, Grade 1, n=109, 107
    17
    23
        Baseline, Grade 2, n=230, 228
    25
    23
        Month 1, Grade 2, n=178, 180
    9
    14
        Month 3, Grade 2, n=109, 107
    7
    10
        Baseline, Grade 3, n=230, 228
    2
    4
        Month 1, Grade 3, n=178, 180
    0
    1
    Notes
    [19] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [20] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment for the neurological sign and symptom of dizziness/lightheadedness at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment for the neurological sign and symptom of dizziness/lightheadedness at Baseline, Month 1, and Month 3
    End point description
    The investigator (per CTCAE, version 3.0) assessed participants for dizziness/lightheadedness and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [21]
    228 [22]
    Units: participants
        Baseline, absent, n=230, 228
    160
    151
        Month 1, absent, n=178, 180
    124
    128
        Month 3, absent, n=109, 107
    76
    76
        Baseline, Grade 1, n=230, 228
    45
    47
        Month 1, Grade 1, n=178, 180
    44
    36
        Month 3, Grade 1, n=109, 107
    21
    20
        Baseline, Grade 2, n=230, 228
    21
    26
        Month 1, Grade 2, n=178, 180
    7
    14
        Month 3, Grade 2, n=109, 107
    9
    9
        Baseline, Grade 3, n=230, 228
    4
    4
        Month 1, Grade 3, n=178, 180
    3
    2
        Month 3, Grade 3, n=109, 107
    3
    2
    Notes
    [21] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [22] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment for the neurological sign and symptom of vertigo at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment for the neurological sign and symptom of vertigo at Baseline, Month 1, and Month 3
    End point description
    The investigator (per CTCAE, version 3.0) assessed participants for vertigo and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [23]
    228 [24]
    Units: participants
        Baseline, absent, n=230, 228
    180
    173
        Month 1, absent, n=178, 180
    148
    150
        Month 3, absent, n=109, 107
    90
    86
        Baseline, Grade 1, n=230, 228
    26
    30
        Month 1, Grade 1, n=178, 180
    19
    19
        Month 3, Grade 1, n=109, 107
    14
    13
        Baseline, Grade 2, n=230, 228
    19
    22
        Month 1, Grade 2, n=178, 180
    7
    9
        Month 3, Grade 2, n=109, 107
    4
    6
        Baseline, Grade 3, n=230, 228
    5
    3
        Month 1, Grade 3, n=178, 180
    3
    2
        Month 3, Grade 3, n=109, 107
    1
    2
        Month 1, Grade 4, n=178, 180
    1
    0
    Notes
    [23] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [24] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment for the neurological sign and symptom of nausea/vomiting at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment for the neurological sign and symptom of nausea/vomiting at Baseline, Month 1, and Month 3
    End point description
    The investigator (per CTCAE, version 3.0) assessed participants for nausea/vomiting and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [25]
    228 [26]
    Units: participants
        Baseline, absent, n=230, 228
    203
    192
        Month 1, absent, n=178, 180
    151
    162
        Month 3, absent, n=109, 107
    88
    93
        Baseline, Grade 1, n=230, 228
    19
    22
        Month 1, Grade 1, n=178, 180
    20
    15
        Month 3, Grade 1, n=109, 107
    14
    11
        Baseline, Grade 2, n=230, 228
    7
    10
        Month 1, Grade 2, n=178, 180
    6
    3
        Month 3, Grade 2, n=109, 107
    6
    3
        Baseline, Grade 3, n=230, 228
    1
    4
        Month 1, Grade 3, n=178, 180
    1
    0
        Month 3, Grade 5, n=109, 107
    1
    0
    Notes
    [25] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [26] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment for the neurological sign and symptom of visual problem at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment for the neurological sign and symptom of visual problem at Baseline, Month 1, and Month 3
    End point description
    The investigator (per CTCAE, version 3.0) assessed participants for visual problem and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [27]
    228 [28]
    Units: participants
        Baseline, absent, n=230, 228
    181
    189
        Month 1, absent, n=178, 180
    148
    154
        Month 3, absent, n=109, 107
    93
    93
        Baseline, Grade 1, n=230, 228
    22
    25
        Month 1, Grade 1, n=178, 180
    16
    19
        Month 3, Grade 1, n=109, 107
    12
    10
        Baseline, Grade 2, n=230, 228
    20
    13
        Month 1, Grade 2, n=178, 180
    11
    6
        Month 3, Grade 2, n=109, 107
    4
    3
        Baseline, Grade 3, n=230, 228
    5
    1
        Month 1, Grade 3, n=178, 180
    2
    1
        Month 3, Grade 3, n=109, 107
    0
    1
        Baseline, Grade 4, n=230, 228
    2
    0
        Month 1, Grade 4, n=178, 180
    1
    0
    Notes
    [27] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [28] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment for the neurological sign and symptom of seizure at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment for the neurological sign and symptom of seizure at Baseline, Month 1, and Month 3
    End point description
    The investigator (per CTCAE, version 3.0) assessed participants for seizure and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [29]
    228 [30]
    Units: participants
        Baseline, absent, n=230, 228
    218
    216
        Month 1, absent, n=178, 180
    175
    178
        Month 3, absent, n=109, 107
    109
    101
        Baseline, Grade 1, n=230, 228
    4
    6
        Month 1, Grade 1, n=178, 180
    2
    1
        Month 3, Grade 1, n=109, 107
    0
    4
        Baseline, Grade 2, n=230, 228
    6
    6
        Month 1, Grade 2, n=178, 180
    1
    1
        Month 3, Grade 2, n=109, 107
    0
    2
        Baseline, Grade 3, n=230, 228
    1
    0
        Baseline, Grade 4, n=230, 228
    1
    0
    Notes
    [29] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [30] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment for the neurological sign and symptom of other neurological symptoms at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment for the neurological sign and symptom of other neurological symptoms at Baseline, Month 1, and Month 3
    End point description
    The investigator (per CTCAE, version 3.0) assessed participants for other neurological symptoms and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    229 [31]
    228 [32]
    Units: participants
        Baseline, absent, n=229, 228
    219
    214
        Month 1, absent, n=177, 180
    165
    171
        Month 3, absent, n=109, 107
    99
    101
        Baseline, Grade 1, n=229, 228
    2
    5
        Month 1, Grade 1, n=177, 180
    2
    6
        Month 3, Grade 1, n=109, 107
    6
    5
        Baseline, Grade 2, n=229, 228
    7
    8
        Month 1, Grade 2, n=177, 180
    8
    1
        Month 3, Grade 2, n=109, 107
    3
    1
        Baseline, Grade 3, n=229, 228
    1
    1
        Month 1, Grade 3, n=177, 180
    2
    1
        Month 1, Grade 4, n=177, 180
    0
    1
        Month 3, Grade 5, n=109, 107
    1
    0
    Notes
    [31] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [32] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of cranial nerves II-XII at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of cranial nerves II-XII at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of cranial nerves II-XII and assigned each participant to one of the following categories: normal; present, not interfering with ADLs; present, interfering with ADLs; life threatening, disabling. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    229 [33]
    225 [34]
    Units: participants
        Baseline, normal, n=229, 225
    218
    211
        Month 1, normal, n=177, 179
    172
    169
        Month 3, normal, n=109, 107
    106
    102
        Baseline, present, not interfering, n=229, 225
    11
    10
        Month 1, present, not interfering, n=177, 179
    4
    6
        Month 3, present, not interfering, n=109, 107
    3
    2
        Baseline, present, interfering, n=229, 225
    0
    4
        Month 1, present, interfering, n=177, 179
    1
    4
        Month 3, present, interfering, n=109, 107
    0
    3
    Notes
    [33] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [34] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of language (dysphasia or aphasia) at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of language (dysphasia or aphasia) at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of language (dysphasia or aphasia) and assigned each participant to one of the following categories: absent; awareness of receptive or expressive aphasia, not impairing ability to communicate (not impaired); receptive or expressive dysphasia, impairing ability to communicate (impaired); inability to communicate (unable). If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [35]
    228 [36]
    Units: participants
        Baseline, absent, n=230, 228
    211
    215
        Month 1, absent, n=178, 180
    169
    173
        Month 3, absent, n=109, 107
    105
    98
        Baseline, not impaired, n=230, 228
    15
    10
        Month 1, not impaired, n=178, 180
    6
    5
        Month 3, not impaired, n=109, 107
    3
    7
        Baseline, impaired, n=230, 228
    3
    3
        Month 1, impaired, n=178, 180
    3
    2
        Month 3, impaired, n=109, 107
    1
    0
        Baseline, unable, n=230, 228
    1
    0
        Month 3, unable, n=109, 107
    0
    2
    Notes
    [35] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [36] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of strength (right upper extremity) at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of strength (right upper extremity) at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of strength (right upper extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [37]
    228 [38]
    Units: participants
        Baseline, normal, n=230, 228
    203
    195
        Month 1, normal, n=178, 179
    153
    159
        Month 3, normal, n=109, 107
    93
    89
        Baseline, Grade 1, n=230, 228
    15
    16
        Month 1, Grade 1, n=178, 179
    13
    12
        Month 3, Grade 1, n=109, 107
    10
    10
        Baseline, Grade 2, n=230, 228
    6
    12
        Month 1, Grade 2, n=178, 179
    6
    5
        Month 3, Grade 2, n=109, 107
    4
    5
        Baseline, Grade 3, n=230, 228
    5
    5
        Month 1, Grade 3, n=178, 179
    4
    2
        Month 3, Grade 3, n=109, 107
    2
    3
        Baseline, Grade 4, n=230, 228
    1
    0
        Month 1, Grade 4, n=178, 179
    2
    1
    Notes
    [37] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [38] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of strength (left upper extremity) at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of strength (left upper extremity) at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of strength (left upper extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [39]
    228 [40]
    Units: participants
        Baseline, normal, n=230, 228
    197
    202
        Month 1, normal, n=178, 179
    149
    157
        Month 3, normal, n=109, 107
    90
    86
        Baseline, Grade 1, n=230, 228
    16
    13
        Month 1, Grade 1, n=178, 179
    16
    13
        Month 3, Grade 1, n=109, 107
    10
    11
        Baseline, Grade 2, n=230, 228
    11
    8
        Month 1, Grade 2, n=178, 179
    8
    5
        Month 3, Grade 2, n=109, 107
    6
    5
        Baseline, Grade 3, n=230, 228
    6
    4
        Month 1, Grade 3, n=178, 179
    3
    2
        Month 3, Grade 3, n=109, 107
    3
    4
        Baseline, Grade 4, n=230, 228
    0
    1
        Month 1, Grade 4, n=178, 179
    2
    2
        Month 3, Grade 4, n=109, 107
    0
    1
    Notes
    [39] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [40] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of strength (right lower extremity) at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of strength (right lower extremity) at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of strength (right lower extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [41]
    228 [42]
    Units: participants
        Baseline, normal, n=230, 228
    196
    189
        Month 1, normal, n=178, 180
    137
    145
        Month 3, normal, n=109, 107
    81
    80
        Baseline, Grade 1, n=230, 228
    20
    19
        Month 1, Grade 1, n=178, 180
    17
    15
        Month 3, Grade 1, n=109, 107
    12
    11
        Baseline, Grade 2, n=230, 228
    9
    16
        Month 1, Grade 2, n=178, 180
    11
    19
        Month 3, Grade 2, n=109, 107
    11
    11
        Baseline, Grade 3, n=230, 228
    3
    4
        Month 1, Grade 3, n=178, 180
    9
    0
        Month 3, Grade 3, n=109, 107
    4
    3
        Baseline, Grade 4, n=230, 228
    2
    0
        Month 1, Grade 4, n=178, 180
    4
    1
        Month 3, Grade 4, n=109, 107
    1
    2
    Notes
    [41] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [42] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of strength (left lower extremity) at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of strength (left lower extremity) at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of strength (left lower extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [43]
    228 [44]
    Units: participants
        Baseline, normal, n=230, 228
    182
    190
        Month 1, normal, n=178, 179
    128
    143
        Month 3, normal, n=109, 107
    76
    73
        Baseline, Grade 1, n=230, 228
    28
    18
        Month 1, Grade 1, n=178, 179
    26
    13
        Month 3, Grade 1, n=109, 107
    11
    11
        Baseline, Grade 2, n=230, 228
    15
    15
        Month 1, Grade 2, n=178, 179
    11
    17
        Month 3, Grade 2, n=109, 107
    14
    14
        Baseline, Grade 3, n=230, 228
    4
    3
        Month 1, Grade 3, n=178, 179
    10
    4
        Month 3, Grade 3, n=109, 107
    6
    5
        Baseline, Grade 4, n=230, 228
    1
    2
        Month 1, Grade 4, n=178, 179
    3
    2
        Month 3, Grade 4, n=109, 107
    2
    4
    Notes
    [43] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [44] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of sensation at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of sensation at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of sensation and assigned each participant to one of the following categories: normal; loss of deep tendon reflexes or paresthesia, but not interfering with function (not interfering with function); objective sensory loss or paresthesia interfering with function, but not interfering with ADLs (interfering with function); sensory loss or paresthesia interfering with ADLs (intefering with ADLs); permanent sensory loss that interferes with function (permanent sensory loss). If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [45]
    228 [46]
    Units: participants
        Baseline (BL), normal, n=230, 228
    197
    192
        Month (M) 1, normal, n=178, 180
    144
    159
        Month 3, normal, n=109, 107
    100
    94
        BL, not interfering with function, n=230, 228
    26
    26
        M 1, not interfering with function, n=178, 180
    22
    15
        M 3, not interfering with function, n=109, 107
    5
    9
        BL, interfering with function, n=230, 228
    3
    6
        M 1, interfering with function, n=178, 180
    7
    4
        M 3, interfering with function, n=109, 107
    2
    2
        Baseline, interfering with ADLs, n=230, 228
    4
    3
        Month 1, interfering with ADLs, n=178, 180
    5
    2
        Month 3, interfering with ADLs, n=109, 107
    2
    2
        Baseline, permanent sensory loss, n=230, 228
    0
    1
    Notes
    [45] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [46] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of ataxia (right upper extremity: finger to nose testing) at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of ataxia (right upper extremity: finger to nose testing) at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of ataxia (right upper extremity: finger to nose testing) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    229 [47]
    228 [48]
    Units: participants
        Baseline, normal, n=229, 228
    206
    198
        Month 1, normal, n=178, 179
    166
    166
        Month 3, normal, n=109, 107
    103
    95
        Baseline, Grade 1, n=229, 228
    13
    17
        Month 1, Grade 1, n=178, 179
    7
    6
        Month 3, Grade 1, n=109, 107
    6
    5
        Baseline, Grade 2, n=229, 228
    5
    12
        Month 1, Grade 2, n=178, 179
    3
    6
        Month 3, Grade 2, n=109, 107
    0
    5
        Baseline, Grade 3, n=229, 228
    3
    1
        Month 3, Grade 3, n=109, 107
    0
    1
        Baseline, Grade 4, n=229, 228
    2
    0
        Month 1, Grade 4, n=178, 179
    2
    1
        Month 3, Grade 4, n=109, 107
    0
    1
    Notes
    [47] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [48] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of ataxia (left upper extremity: finger to nose testing) at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of ataxia (left upper extremity: finger to nose testing) at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of ataxia (left upper extremity: finger to nose testing) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [49]
    227 [50]
    Units: participants
        Baseline, normal, n=230, 227
    199
    201
        Month 1, normal, n=178, 178
    156
    162
        Month 3, normal, n=109, 107
    97
    94
        Baseline, Grade 1, n=230, 227
    15
    13
        Month 1, Grade 1, n=178, 178
    14
    9
        Month 3, Grade 1, n=109, 107
    10
    6
        Baseline, Grade 2, n=230, 227
    8
    7
        Month 1, Grade 2, n=178, 178
    6
    3
        Month 3, Grade 2, n=109, 107
    2
    3
        Baseline, Grade 3, n=230, 227
    8
    4
        Month 1, Grade 3, n=178, 178
    0
    3
        Month 3, Grade 3, n=109, 107
    0
    1
        Baseline, Grade 4, n=230, 227
    0
    2
        Month 1, Grade 4, n=178, 178
    2
    1
        Month 3, Grade 4, n=109, 107
    0
    3
    Notes
    [49] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [50] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of ataxia (gait) at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of ataxia (gait) at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of ataxia (gait) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [51]
    227 [52]
    Units: participants
        Baseline, normal, n=230, 227
    172
    178
        Month 1, normal, n=178, 179
    138
    147
        Month 3, normal, n=108, 107
    85
    76
        Baseline, Grade 1, n=230, 227
    13
    22
        Month 1, Grade 1, n=178, 179
    16
    13
        Month 3, Grade 1, n=108, 107
    9
    10
        Baseline, Grade 2, n=230, 227
    37
    20
        Month 1, Grade 2, n=178, 179
    14
    14
        Month 3, Grade 2, n=108, 107
    9
    12
        Baseline, Grade 3, n=230, 227
    6
    6
        Month 1, Grade 3, n=178, 179
    7
    3
        Month 3, Grade 3, n=108, 107
    4
    5
        Baseline, Grade 4, n=230, 227
    2
    1
        Month 1, Grade 4, n=178, 179
    3
    2
        Month 3, Grade 4, n=108, 107
    1
    4
    Notes
    [51] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [52] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated investigator assessment of ataxia (balance) at Baseline, Month 1, and Month 3

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    End point title
    Number of participants with the indicated investigator assessment of ataxia (balance) at Baseline, Month 1, and Month 3
    End point description
    The investigator assessed participants' status of ataxia (balance) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    230 [53]
    228 [54]
    Units: participants
        Baseline, normal, n=230, 228
    153
    152
        Month 1, normal, n=178, 178
    131
    128
        Month 3, normal, n=108, 107
    78
    75
        Baseline, Grade 1, n=230, 228
    37
    44
        Month 1, Grade 1, n=178, 178
    23
    28
        Month 3, Grade 1, n=108, 107
    17
    13
        Baseline, Grade 2, n=230, 228
    27
    23
        Month 1, Grade 2, n=178, 178
    13
    16
        Month 3, Grade 2, n=108, 107
    8
    9
        Baseline, Grade 3, n=230, 228
    10
    7
        Month 1, Grade 3, n=178, 178
    8
    5
        Month 3, Grade 3, n=108, 107
    4
    5
        Baseline, Grade 4, n=230, 228
    3
    2
        Month 1, Grade 4, n=178, 178
    3
    1
        Month 3, Grade 4, n=108, 107
    1
    5
    Notes
    [53] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    [54] - ITT Population. Only those participants who were assessed at the indicated time point were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with any adverse event (AE; both serious and non-serious) or serious adverse event (SAE)

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    End point title
    Number of participants with any adverse event (AE; both serious and non-serious) or serious adverse event (SAE)
    End point description
    An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect. For a list of all SAEs and AEs , see the SAE/AE module of this results summary. Participants were analyzed by the actual treatment received, even if this differed from the treatment to which they were randomized.
    End point type
    Secondary
    End point timeframe
    From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    235 [55]
    233 [56]
    Units: participants
        AE
    204
    148
        SAE
    96
    43
    Notes
    [55] - Modified ITT Population: all randomized par. who received at least one dose of randomized therapy.
    [56] - Modified ITT Population: all randomized par. who received at least one dose of randomized therapy.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated worst-case change from Baseline in the indicated chemistry parameters with respect to the normal range

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    End point title
    Number of participants with the indicated worst-case change from Baseline in the indicated chemistry parameters with respect to the normal range
    End point description
    The worst-case change from Baseline in chemistry parameters was measured as decrease to low (DTL), change to normal or no change (CTN/NC), or increase to high (ITH). The worst-case change value could have been measured at any point during the on-therapy period. Participants are counted twice if the participant "Decreased to Low" and "Increased to High" during the on-therapy period. Modified ITT Population. Only those participants with available laboratory values (indicated by the "n" in the category titles) were analyzed. Different participants may have been analyzed for different parameters; therefore, the overall number of participants analyzed reflects everyone in the Modified ITT Population.
    End point type
    Secondary
    End point timeframe
    From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    235 [57]
    233 [58]
    Units: participants
        Chloride, DTL, n=169, 171
    32
    21
        Chloride, CTN/NC, n=169, 171
    116
    144
        Chloride, ITH, n=169, 171
    22
    6
        Creatinine clearance, DTL, n=159, 145
    26
    9
        Creatinine clearance, CTN/NC, n=159, 145
    121
    134
        Creatinine clearance, ITH, n=159, 145
    15
    2
        Lactate dehydrogenase, DTL, n=169, 168
    8
    1
        Lactate dehydrogenase, CTN/NC, n=169, 168
    117
    127
        Lactate dehydrogenase, ITH, n=169, 168
    47
    40
        Total protein, DTL, n=171, 175
    48
    36
        Total protein, CTN/NC, n=171, 175
    119
    137
        Total protein, ITH, n=171, 175
    4
    2
        Urea/blood urea nitrogen, DTL, n=178, 179
    7
    4
        Urea/blood urea nitrogen, CTN/NC, n=178, 179
    139
    152
        Urea/blood urea nitrogen, ITH, n=178, 179
    33
    24
        Uric acid, DTL, n=159, 152
    21
    12
        Uric acid, CTN/NC, n=159, 152
    125
    134
        Uric acid, ITH, n=159, 152
    13
    6
        Basophils, DTL, n=215, 211
    7
    1
        Basophils, CTN/NC, n=215, 211
    186
    200
        Basophils, ITH, n=215, 211
    25
    10
        Eosinophils, DTL, n=214, 211
    28
    12
        Eosinophils, CTN/NC, n=214, 211
    182
    191
        Eosinophils, ITH, n=214, 211
    4
    8
        Hematocrit, DTL, n=215, 212
    98
    38
        Hematocrit, CTN/NC, n=215, 212
    117
    169
        Hematocrit, ITH, n=215, 212
    1
    6
        Monocytes, DTL, n=216, 212
    84
    17
        Monocytes, CTN/NC, n=216, 212
    119
    161
        Monocytes, ITH, n=216, 212
    54
    37
        Red Blood Cell Count, DTL, n=216, 212
    103
    38
        Red Blood Cell Count, CTN/NC, n=216, 212
    113
    171
        Red Blood Cell Count, ITH, n=216, 212
    0
    4
    Notes
    [57] - Modified ITT Population
    [58] - Modified ITT Population
    No statistical analyses for this end point

    Secondary: Lesion assessment and measurement

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    End point title
    Lesion assessment and measurement
    End point description
    Lesions were assessed per WHO criteria. For lesion assessment data, see the outcome measure entitled "Number of participants with a complete response (CR) or a partial response (PR) (central nervous system [CNS]-radiologic)."
    End point type
    Secondary
    End point timeframe
    From the time of Randomization until the time of CR or PR (up to 75 weeks)
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    0 [59]
    0 [60]
    Units: participants
    Notes
    [59] - ITT Population
    [60] - ITT Population
    No statistical analyses for this end point

    Secondary: Brain symptoms

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    End point title
    Brain symptoms
    End point description
    Brain symptoms were assessed as the number of participants with neurological signs and symptoms. For brain symptom data, see the outcome measures entitled "Number of participants with the indicated investigator assessment for the neurological sign and symptom of X at Baseline, Month 1, and Month 3."
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, and Month 3
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    0 [61]
    0 [62]
    Units: participants
    Notes
    [61] - ITT Population
    [62] - ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants who died or progressed

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    End point title
    Number of participants who died or progressed
    End point description
    Disease-related events were measured as the number of participants who died or progressed. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. Data were analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before an event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.
    End point type
    Secondary
    End point timeframe
    From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)
    End point values
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Number of subjects analysed
    235 [63]
    233 [64]
    Units: participants
    179
    161
    Notes
    [63] - mITT Population
    [64] - mITT Population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment AEs
    Adverse event reporting additional description
    Serious adverse events (SAEs) and non-serious AEs were collected in members of the Modified Intent-to-Treat Population, comprised of all randomized participants (par.) who received at least one dose of randomized therapy. Par. were analyzed by the actual treatment received, even if it differed from the treatment to which they were randomized.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Chemoradiation: Topotecan plus WBRT
    Reporting group description
    Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.

    Reporting group title
    Radiation: WBRT Alone
    Reporting group description
    Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.

    Serious adverse events
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    96 / 235 (40.85%)
    43 / 233 (18.45%)
         number of deaths (all causes)
    212
    205
         number of deaths resulting from adverse events
    Vascular disorders
    Arterial thrombosis limb
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior vena cava syndrome
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Deep vein thrombosis
         subjects affected / exposed
    3 / 235 (1.28%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Non-small cell lung cancer
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Performance status decreased
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    5 / 235 (2.13%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 235 (2.13%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    3 / 5
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Face injury
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation pneumonitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure acute
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery insufficiency
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Myocardial ischaemia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pericarditis
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 235 (0.43%)
    4 / 233 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    0 / 235 (0.00%)
    3 / 233 (1.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Aspiration
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchial obstruction
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypoxia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infiltration
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    3 / 235 (1.28%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    3 / 235 (1.28%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    13 / 235 (5.53%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    13 / 13
    0 / 0
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    Pancytopenia
         subjects affected / exposed
    6 / 235 (2.55%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    6 / 6
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Agranulocytosis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphopenia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    8 / 235 (3.40%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    8 / 8
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    16 / 235 (6.81%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    15 / 17
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    22 / 235 (9.36%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    23 / 23
    1 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    22 / 235 (9.36%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    25 / 25
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Syncope
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Grand mal convulsion
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Paraplegia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    6 / 235 (2.55%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    5 / 6
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Nausea
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal haemorrhage
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Intestinal perforation
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Stevens-Johnson syndrome
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypernatraemia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    5 / 235 (2.13%)
    3 / 233 (1.29%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Oropharyngitis fungal
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peridiverticular abscess
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    7 / 235 (2.98%)
    6 / 233 (2.58%)
         occurrences causally related to treatment / all
    2 / 7
    0 / 6
         deaths causally related to treatment / all
    1 / 3
    0 / 3
    Sepsis
         subjects affected / exposed
    4 / 235 (1.70%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Chemoradiation: Topotecan plus WBRT Radiation: WBRT Alone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    192 / 235 (81.70%)
    139 / 233 (59.66%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    6 / 235 (2.55%)
    0 / 233 (0.00%)
         occurrences all number
    7
    0
    Hypertension
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Flushing
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Phlebitis
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Haematoma
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Hot flush
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Orthostatic hypotension
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Thrombophlebitis superficial
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 233 (0.86%)
         occurrences all number
    1
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    3 / 235 (1.28%)
    3 / 233 (1.29%)
         occurrences all number
    3
    3
    Tumour pain
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Metastases to skin
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    39 / 235 (16.60%)
    37 / 233 (15.88%)
         occurrences all number
    40
    38
    Asthenia
         subjects affected / exposed
    29 / 235 (12.34%)
    19 / 233 (8.15%)
         occurrences all number
    29
    21
    Oedema peripheral
         subjects affected / exposed
    15 / 235 (6.38%)
    15 / 233 (6.44%)
         occurrences all number
    16
    16
    Pyrexia
         subjects affected / exposed
    13 / 235 (5.53%)
    5 / 233 (2.15%)
         occurrences all number
    14
    5
    Mucosal inflammation
         subjects affected / exposed
    7 / 235 (2.98%)
    0 / 233 (0.00%)
         occurrences all number
    9
    0
    Gait disturbance
         subjects affected / exposed
    2 / 235 (0.85%)
    4 / 233 (1.72%)
         occurrences all number
    2
    4
    Chest pain
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 233 (0.86%)
         occurrences all number
    1
    3
    Face oedema
         subjects affected / exposed
    1 / 235 (0.43%)
    3 / 233 (1.29%)
         occurrences all number
    1
    3
    Pain
         subjects affected / exposed
    1 / 235 (0.43%)
    3 / 233 (1.29%)
         occurrences all number
    1
    3
    Chills
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Spinal pain
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Chest discomfort
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Early satiety
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Gravitational oedema
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Hyperthermia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Influenza like illness
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Local swelling
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Localised oedema
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Malaise
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Mucosal erosion
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Oedema
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Swelling
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    17 / 235 (7.23%)
    19 / 233 (8.15%)
         occurrences all number
    17
    20
    Confusional state
         subjects affected / exposed
    7 / 235 (2.98%)
    11 / 233 (4.72%)
         occurrences all number
    7
    11
    Anxiety
         subjects affected / exposed
    4 / 235 (1.70%)
    1 / 233 (0.43%)
         occurrences all number
    4
    1
    Depression
         subjects affected / exposed
    2 / 235 (0.85%)
    2 / 233 (0.86%)
         occurrences all number
    2
    2
    Mood altered
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Nervousness
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Sleep disorder
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    2
    Delusion
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Depressed mood
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Disorientation
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Initial insomnia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Mental disorder
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Staring
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Epididymitis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Prostatitis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Thermal burn
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Contusion
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Incision site pain
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Overdose
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Radiation skin injury
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Skin wound
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Weight decreased
         subjects affected / exposed
    18 / 235 (7.66%)
    8 / 233 (3.43%)
         occurrences all number
    21
    8
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    3 / 235 (1.28%)
    2 / 233 (0.86%)
         occurrences all number
    3
    2
    Platelet count decreased
         subjects affected / exposed
    4 / 235 (1.70%)
    1 / 233 (0.43%)
         occurrences all number
    4
    1
    Haemoglobin decreased
         subjects affected / exposed
    3 / 235 (1.28%)
    1 / 233 (0.43%)
         occurrences all number
    3
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Weight increased
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Blood glucose increased
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Neutrophil count decreased
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    White blood cell count decreased
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Bacterial test positive
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Blood magnesium increased
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Blood phosphorus decreased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Blood phosphorus increased
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Blood urea increased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Blood uric acid increased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Body temperature increased
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Breath sounds abnormal
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    International normalised ratio increased
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    3 / 235 (1.28%)
    2 / 233 (0.86%)
         occurrences all number
    3
    2
    Tachycardia
         subjects affected / exposed
    2 / 235 (0.85%)
    3 / 233 (1.29%)
         occurrences all number
    2
    3
    Cardiac failure
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Palpitations
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Angina pectoris
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Sinus tachycardia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    31 / 235 (13.19%)
    20 / 233 (8.58%)
         occurrences all number
    32
    21
    Cough
         subjects affected / exposed
    26 / 235 (11.06%)
    17 / 233 (7.30%)
         occurrences all number
    29
    18
    Epistaxis
         subjects affected / exposed
    8 / 235 (3.40%)
    2 / 233 (0.86%)
         occurrences all number
    9
    2
    Haemoptysis
         subjects affected / exposed
    3 / 235 (1.28%)
    7 / 233 (3.00%)
         occurrences all number
    3
    7
    Oropharyngeal pain
         subjects affected / exposed
    5 / 235 (2.13%)
    3 / 233 (1.29%)
         occurrences all number
    5
    3
    Hiccups
         subjects affected / exposed
    3 / 235 (1.28%)
    2 / 233 (0.86%)
         occurrences all number
    3
    2
    Dyspnoea exertional
         subjects affected / exposed
    1 / 235 (0.43%)
    3 / 233 (1.29%)
         occurrences all number
    1
    3
    Hypoxia
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    3
    1
    Productive cough
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 233 (0.86%)
         occurrences all number
    1
    2
    Dysphonia
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Lung infiltration
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Pleural effusion
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Pulmonary embolism
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Wheezing
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Bronchitis chronic
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Hydrothorax
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Increased upper airway secretion
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Laryngeal inflammation
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Pneumothorax
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Rales
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Respiratory failure
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract congestion
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 235 (2.98%)
    1 / 233 (0.43%)
         occurrences all number
    7
    1
    Thrombocytopenia
         subjects affected / exposed
    5 / 235 (2.13%)
    1 / 233 (0.43%)
         occurrences all number
    5
    1
    Neutropenia
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 233 (0.00%)
         occurrences all number
    4
    0
    Leukopenia
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Coagulopathy
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Febrile neutropenia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Pancytopenia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    27 / 235 (11.49%)
    28 / 233 (12.02%)
         occurrences all number
    33
    32
    Dizziness
         subjects affected / exposed
    27 / 235 (11.49%)
    19 / 233 (8.15%)
         occurrences all number
    29
    22
    Somnolence
         subjects affected / exposed
    14 / 235 (5.96%)
    14 / 233 (6.01%)
         occurrences all number
    14
    15
    Hypoaesthesia
         subjects affected / exposed
    6 / 235 (2.55%)
    11 / 233 (4.72%)
         occurrences all number
    6
    12
    Ataxia
         subjects affected / exposed
    8 / 235 (3.40%)
    6 / 233 (2.58%)
         occurrences all number
    8
    6
    Coordination abnormal
         subjects affected / exposed
    7 / 235 (2.98%)
    4 / 233 (1.72%)
         occurrences all number
    7
    4
    Tremor
         subjects affected / exposed
    6 / 235 (2.55%)
    4 / 233 (1.72%)
         occurrences all number
    6
    4
    Paraesthesia
         subjects affected / exposed
    5 / 235 (2.13%)
    4 / 233 (1.72%)
         occurrences all number
    5
    4
    Amnesia
         subjects affected / exposed
    2 / 235 (0.85%)
    6 / 233 (2.58%)
         occurrences all number
    2
    6
    Dysgeusia
         subjects affected / exposed
    6 / 235 (2.55%)
    2 / 233 (0.86%)
         occurrences all number
    6
    2
    Aphasia
         subjects affected / exposed
    1 / 235 (0.43%)
    6 / 233 (2.58%)
         occurrences all number
    1
    6
    Balance disorder
         subjects affected / exposed
    0 / 235 (0.00%)
    7 / 233 (3.00%)
         occurrences all number
    0
    7
    Convulsion
         subjects affected / exposed
    4 / 235 (1.70%)
    1 / 233 (0.43%)
         occurrences all number
    5
    2
    Epilepsy
         subjects affected / exposed
    1 / 235 (0.43%)
    3 / 233 (1.29%)
         occurrences all number
    1
    6
    Neuropathy peripheral
         subjects affected / exposed
    2 / 235 (0.85%)
    2 / 233 (0.86%)
         occurrences all number
    2
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    2 / 235 (0.85%)
    2 / 233 (0.86%)
         occurrences all number
    2
    2
    Speech disorder
         subjects affected / exposed
    1 / 235 (0.43%)
    3 / 233 (1.29%)
         occurrences all number
    1
    3
    Syncope
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Brain oedema
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Convulsions local
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Hemiparesis
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Hemiplegia
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Hypersomnia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    2
    Loss of consciousness
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Memory impairment
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Psychomotor hyperactivity
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Ageusia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Alcoholic seizure
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Burning sensation
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Cognitive disorder
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Dysarthria
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Facial paresis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Hypotonia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Mental impairment
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Monoplegia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Neuritis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Paresis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Partial seizures
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Peripheral motor neuropathy
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Visual field defect
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Eye disorders
    Vision blurred
         subjects affected / exposed
    4 / 235 (1.70%)
    8 / 233 (3.43%)
         occurrences all number
    4
    8
    Visual acuity reduced
         subjects affected / exposed
    3 / 235 (1.28%)
    2 / 233 (0.86%)
         occurrences all number
    3
    2
    Visual impairment
         subjects affected / exposed
    2 / 235 (0.85%)
    2 / 233 (0.86%)
         occurrences all number
    2
    3
    Asthenopia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Blindness
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Eye inflammation
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Eye pain
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Myopia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Retinal vascular disorder
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    4 / 235 (1.70%)
    3 / 233 (1.29%)
         occurrences all number
    4
    3
    Tinnitus
         subjects affected / exposed
    4 / 235 (1.70%)
    0 / 233 (0.00%)
         occurrences all number
    4
    0
    Ear pain
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Ear pruritus
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Auricular swelling
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Deafness
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Hearing impaired
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Hypoacusis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    64 / 235 (27.23%)
    30 / 233 (12.88%)
         occurrences all number
    84
    32
    Vomiting
         subjects affected / exposed
    37 / 235 (15.74%)
    24 / 233 (10.30%)
         occurrences all number
    46
    29
    Dyspepsia
         subjects affected / exposed
    17 / 235 (7.23%)
    10 / 233 (4.29%)
         occurrences all number
    17
    11
    Diarrhoea
         subjects affected / exposed
    19 / 235 (8.09%)
    8 / 233 (3.43%)
         occurrences all number
    19
    8
    Constipation
         subjects affected / exposed
    8 / 235 (3.40%)
    10 / 233 (4.29%)
         occurrences all number
    8
    10
    Abdominal pain
         subjects affected / exposed
    4 / 235 (1.70%)
    6 / 233 (2.58%)
         occurrences all number
    5
    6
    Stomatitis
         subjects affected / exposed
    7 / 235 (2.98%)
    1 / 233 (0.43%)
         occurrences all number
    7
    1
    Abdominal pain upper
         subjects affected / exposed
    2 / 235 (0.85%)
    3 / 233 (1.29%)
         occurrences all number
    2
    3
    Dysphagia
         subjects affected / exposed
    2 / 235 (0.85%)
    3 / 233 (1.29%)
         occurrences all number
    2
    3
    Dry mouth
         subjects affected / exposed
    2 / 235 (0.85%)
    2 / 233 (0.86%)
         occurrences all number
    2
    2
    Abdominal distension
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Flatulence
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    3
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 233 (0.00%)
         occurrences all number
    3
    0
    Glossodynia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Mouth ulceration
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Abdominal discomfort
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Aphthous stomatitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Ascites
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Breath odour
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Faecal incontinence
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Faeces discoloured
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Gastritis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Gingival pain
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Haematochezia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Hyperchlorhydria
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Oesophageal pain
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Oral pain
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Retching
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Dysuria
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Pollakiuria
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Chromaturia
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Incontinence
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Proteinuria
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Urinary bladder haemorrhage
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Urinary incontinence
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Urinary retention
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    4 / 235 (1.70%)
    1 / 233 (0.43%)
         occurrences all number
    4
    1
    Pruritus
         subjects affected / exposed
    5 / 235 (2.13%)
    0 / 233 (0.00%)
         occurrences all number
    5
    0
    Rash
         subjects affected / exposed
    2 / 235 (0.85%)
    3 / 233 (1.29%)
         occurrences all number
    2
    3
    Dry skin
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 233 (0.86%)
         occurrences all number
    1
    2
    Ecchymosis
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    2
    Swelling face
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 233 (0.86%)
         occurrences all number
    1
    2
    Acne
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Night sweats
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Skin disorder
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Skin ulcer
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Dermatitis allergic
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Haemorrhage subcutaneous
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Increased tendency to bruise
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Petechiae
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Rash papular
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Skin exfoliation
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Alopecia
         subjects affected / exposed
    21 / 235 (8.94%)
    17 / 233 (7.30%)
         occurrences all number
    21
    17
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    29 / 235 (12.34%)
    22 / 233 (9.44%)
         occurrences all number
    41
    29
    Pain in extremity
         subjects affected / exposed
    8 / 235 (3.40%)
    6 / 233 (2.58%)
         occurrences all number
    9
    6
    Arthralgia
         subjects affected / exposed
    6 / 235 (2.55%)
    6 / 233 (2.58%)
         occurrences all number
    6
    6
    Back pain
         subjects affected / exposed
    4 / 235 (1.70%)
    4 / 233 (1.72%)
         occurrences all number
    4
    4
    Muscle spasms
         subjects affected / exposed
    4 / 235 (1.70%)
    2 / 233 (0.86%)
         occurrences all number
    5
    2
    Musculoskeletal pain
         subjects affected / exposed
    4 / 235 (1.70%)
    1 / 233 (0.43%)
         occurrences all number
    4
    1
    Myalgia
         subjects affected / exposed
    2 / 235 (0.85%)
    2 / 233 (0.86%)
         occurrences all number
    2
    2
    Joint swelling
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Neck pain
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Bone pain
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Extremity contracture
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Groin pain
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Muscle atrophy
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Osteoarthritis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    9 / 235 (3.83%)
    3 / 233 (1.29%)
         occurrences all number
    9
    4
    Increased appetite
         subjects affected / exposed
    7 / 235 (2.98%)
    6 / 233 (2.58%)
         occurrences all number
    7
    6
    Hyperglycaemia
         subjects affected / exposed
    4 / 235 (1.70%)
    3 / 233 (1.29%)
         occurrences all number
    5
    3
    Dehydration
         subjects affected / exposed
    2 / 235 (0.85%)
    4 / 233 (1.72%)
         occurrences all number
    2
    4
    Hyponatraemia
         subjects affected / exposed
    3 / 235 (1.28%)
    1 / 233 (0.43%)
         occurrences all number
    3
    1
    Cachexia
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Hypoalbuminaemia
         subjects affected / exposed
    3 / 235 (1.28%)
    0 / 233 (0.00%)
         occurrences all number
    3
    0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 233 (0.86%)
         occurrences all number
    1
    2
    Hypocalcaemia
         subjects affected / exposed
    1 / 235 (0.43%)
    1 / 233 (0.43%)
         occurrences all number
    1
    1
    Hyperkalaemia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Malnutrition
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Polydipsia
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Decreased appetite
         subjects affected / exposed
    28 / 235 (11.91%)
    17 / 233 (7.30%)
         occurrences all number
    28
    17
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    3 / 235 (1.28%)
    4 / 233 (1.72%)
         occurrences all number
    4
    4
    Oral candidiasis
         subjects affected / exposed
    5 / 235 (2.13%)
    2 / 233 (0.86%)
         occurrences all number
    5
    2
    Candidiasis
         subjects affected / exposed
    3 / 235 (1.28%)
    2 / 233 (0.86%)
         occurrences all number
    3
    2
    Oral fungal infection
         subjects affected / exposed
    2 / 235 (0.85%)
    3 / 233 (1.29%)
         occurrences all number
    2
    3
    Oropharyngitis fungal
         subjects affected / exposed
    1 / 235 (0.43%)
    3 / 233 (1.29%)
         occurrences all number
    1
    3
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 235 (1.28%)
    1 / 233 (0.43%)
         occurrences all number
    3
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 235 (0.43%)
    2 / 233 (0.86%)
         occurrences all number
    1
    2
    Rhinitis
         subjects affected / exposed
    2 / 235 (0.85%)
    1 / 233 (0.43%)
         occurrences all number
    2
    1
    Bronchitis
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Cystitis
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Herpes zoster
         subjects affected / exposed
    0 / 235 (0.00%)
    2 / 233 (0.86%)
         occurrences all number
    0
    2
    Influenza
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Oesophageal candidiasis
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Oral herpes
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Oropharyngeal candidiasis
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Pharyngitis
         subjects affected / exposed
    2 / 235 (0.85%)
    0 / 233 (0.00%)
         occurrences all number
    2
    0
    Anal fungal infection
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Fungal infection
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Fungal oesophagitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Furuncle
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Herpes simplex
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Infection
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Mastoiditis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Orchitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Otitis media
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Rash pustular
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Soft tissue infection
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Tonsillitis
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Tracheobronchitis
         subjects affected / exposed
    0 / 235 (0.00%)
    1 / 233 (0.43%)
         occurrences all number
    0
    1
    Vaginal infection
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 235 (0.43%)
    0 / 233 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    4 / 235 (1.70%)
    4 / 233 (1.72%)
         occurrences all number
    4
    4

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    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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