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    Clinical Trial Results:
    A therapeutic confirmatory, open-label, multi-center, randomized 2 parallel groups, community-based trial studying the efficacy and safety of levetiracetam (1000 to 3000 mg/day oral tablets 250-500 mg b.i.d.) compared to sodium valproate (1000 to 2000 mg/day oral ER tablets 300-500 mg b.i.d.) and carbamazepine (600 to 1600 mg/day oral CR tablets 200-400 mg b.i.d.) as monotherapy in subjects with newly diagnosed epilepsy.

    Summary
    EudraCT number
    2004-001339-41
    Trial protocol
    AT   FI   SE   SK   IE   CZ   GB   DE   BE   ES   IT   HU   PT   DK  
    Global end of trial date
    13 Oct 2007

    Results information
    Results version number
    v1(current)
    This version publication date
    08 Jul 2016
    First version publication date
    30 Jul 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    N01175
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00175903
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UCB Pharma SA
    Sponsor organisation address
    Chemin du Foriest, Braine, Belgium, 1420 Braine-L’Alleud
    Public contact
    Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, clinicaltrials@ucb.com
    Scientific contact
    Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, 0049 2173 48 15 15, clinicaltrials@ucb.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Dec 2007
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Oct 2007
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the effectiveness of levetiracetam (LEV) in monotherapy compared to the older antiepileptic drugs (sodium valproate (VPA-ER) or carbamazepine (CBZ-CR).
    Protection of trial subjects
    All pertinent aspects of the trial were explained and all questions answered to the satisfaction of the subject or subject’s legally acceptable representative before collecting written informed consent. The consent of both the subject and/or the legally acceptable representative were obtained for subjects under 18 years of age (i.e. in this trial, subjects of 16 years or older where legally permitted). For mentally retarded subjects, the consent of the legally acceptable representative only was obtained. The subject was free to withdraw from the trial at any time without penalty or loss of benefits to which he/she was otherwise entitled.
    Background therapy
    Not applicable.
    Evidence for comparator
    Not applicable.
    Actual start date of recruitment
    09 Feb 2005
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    2 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 98
    Country: Number of subjects enrolled
    Austria: 64
    Country: Number of subjects enrolled
    Belgium: 70
    Country: Number of subjects enrolled
    Czech Republic: 39
    Country: Number of subjects enrolled
    Denmark: 18
    Country: Number of subjects enrolled
    Finland: 31
    Country: Number of subjects enrolled
    France: 72
    Country: Number of subjects enrolled
    Germany: 262
    Country: Number of subjects enrolled
    Greece: 47
    Country: Number of subjects enrolled
    Hungary: 17
    Country: Number of subjects enrolled
    Ireland: 4
    Country: Number of subjects enrolled
    Italy: 165
    Country: Number of subjects enrolled
    Netherlands: 41
    Country: Number of subjects enrolled
    Norway: 56
    Country: Number of subjects enrolled
    Poland: 148
    Country: Number of subjects enrolled
    Romania: 23
    Country: Number of subjects enrolled
    Russian Federation: 55
    Country: Number of subjects enrolled
    Slovakia: 37
    Country: Number of subjects enrolled
    Spain: 69
    Country: Number of subjects enrolled
    Sweden: 36
    Country: Number of subjects enrolled
    Switzerland: 68
    Country: Number of subjects enrolled
    Turkey: 40
    Country: Number of subjects enrolled
    United Kingdom: 101
    Country: Number of subjects enrolled
    Bulgaria: 127
    Worldwide total number of subjects
    1688
    EEA total number of subjects
    1427
    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)
    19
    Adults (18-64 years)
    1441
    From 65 to 84 years
    223
    85 years and over
    5

    Subject disposition

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    Recruitment
    Recruitment details
    The N01175 study began enrollment in February 2005 and concluded in October 2007. Recruitment took place in 24 countries.

    Pre-assignment
    Screening details
    Participant flow and baseline characteristics consist of the Intent-to-Treat (ITT) population, which consists of all randomized subjects regardless of actual intake.

    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
    Levetiracetam
    Arm description
    Daily dose of 1000 to 3000 mg film-coated oral tablets, 250-500 mg twice daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Levetiracetam
    Investigational medicinal product code
    LEV
    Other name
    Keppra
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daily dose of 1000 to 3000 mg film-coated oral tablets, 250-500 mg twice daily.

    Arm title
    Older Antiepileptic Drugs
    Arm description
    Older AEDs consist of CBZ-CR 200 mg and 400 mg and VPA-ER 300 mg and 500 mg.
    Arm type
    Active comparator

    Investigational medicinal product name
    Valproate Extended Release
    Investigational medicinal product code
    VER
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daily dose of 1000-2000 mg ER oral tablets, 300 mg and 500 mg twice daily.

    Investigational medicinal product name
    Carbamazepine Controlled Release
    Investigational medicinal product code
    CBZ-CR
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daily dose of 600-1600 mg CR oral tablets, 200 mg and 400 mg twice daily.

    Number of subjects in period 1
    Levetiracetam Older Antiepileptic Drugs
    Started
    841
    847
    Completed
    639
    627
    Not completed
    202
    220
         SAE, non-fatal + AE, non-serious non-fatal
    2
    2
         Other Reason
    22
    15
         Lack of efficacy
    35
    25
         SAE, non-fatal
    13
    14
         AE, serious fatal
    4
    3
         AE, non-serious non-fatal
    50
    90
         Consent withdrawn by subject
    38
    36
         Unknown AE
    2
    1
         Lost to follow-up
    36
    34

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Levetiracetam
    Reporting group description
    Daily dose of 1000 to 3000 mg film-coated oral tablets, 250-500 mg twice daily.

    Reporting group title
    Older Antiepileptic Drugs
    Reporting group description
    Older AEDs consist of CBZ-CR 200 mg and 400 mg and VPA-ER 300 mg and 500 mg.

    Reporting group values
    Levetiracetam Older Antiepileptic Drugs Total
    Number of subjects
    841 847 1688
    Age Categorical
    Units: Subjects
        Adolescents (12 - <18 years)
    8 11 19
        Adults (18 - <65 years)
    718 723 1441
        Elderly (65 - <85 years)
    112 111 223
        >=85 years
    3 2 5
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    40.61 ± 17.76 40.87 ± 17.8 -
    Gender Categorical
    Units: Subjects
        Female
    375 371 746
        Male
    466 476 942
    Race
    Units: Subjects
        Caucasian
    818 826 1644
        African-american
    8 5 13
        Asian/pacific islander
    8 6 14
        Hispanic
    2 5 7
        Indian/pakistani
    3 2 5
        Other/mixed race
    2 3 5
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    73.08 ± 15.52 74.31 ± 16.16 -
    BMI
    Units: kg/m^2
        arithmetic mean (standard deviation)
    25.04 ± 4.68 25.31 ± 4.6 -
    Height
    Units: cm
        arithmetic mean (standard deviation)
    170.7 ± 10 171.1 ± 9.7 -

    End points

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    End points reporting groups
    Reporting group title
    Levetiracetam
    Reporting group description
    Daily dose of 1000 to 3000 mg film-coated oral tablets, 250-500 mg twice daily.

    Reporting group title
    Older Antiepileptic Drugs
    Reporting group description
    Older AEDs consist of CBZ-CR 200 mg and 400 mg and VPA-ER 300 mg and 500 mg.

    Primary: Time to withdrawal from study medication (starting at V1) as a measure of combined efficacy and safety

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    End point title
    Time to withdrawal from study medication (starting at V1) as a measure of combined efficacy and safety
    End point description
    End point type
    Primary
    End point timeframe
    Visit 1 to End of Study (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    841 [1]
    847 [2]
    Units: Time to Withdrawal
    median (inter-quartile range (Q1-Q3))
        median (inter-quartile range)
    999 (999 to 999)
    999 (999 to 999)
    Notes
    [1] - For this analysis, the value of 999 indicates Not Estimable.
    [2] - For this analysis, the value of 999 indicates Not Estimable.
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Older Antiepileptic Drugs v Levetiracetam
    Number of subjects included in analysis
    1688
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.258
    Method
    Chi-squared
    Parameter type
    Cox proportional hazard
    Point estimate
    0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.74
         upper limit
    1.08

    Secondary: The time to withdrawal comparing Levetiracetam versus the older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release

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    End point title
    The time to withdrawal comparing Levetiracetam versus the older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to End of Study (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    492 [3]
    500 [4]
    Units: Time to Withdrawal
    median (inter-quartile range (Q1-Q3))
        median (inter-quartile range)
    999 (999 to 999)
    999 (999 to 999)
    Notes
    [3] - For this analysis, the value of 999 indicates Not Estimable.
    [4] - For this analysis, the value of 999 indicates Not Estimable.
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    992
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.161
    Method
    Chi-squared
    Parameter type
    Cox proportional hazard
    Point estimate
    0.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.66
         upper limit
    1.07

    Secondary: The time to withdrawal comparing Levetiracetam versus the older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release

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    End point title
    The time to withdrawal comparing Levetiracetam versus the older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to End of Study (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    349 [5]
    347 [6]
    Units: Time to Withdrawal
    median (inter-quartile range (Q1-Q3))
        median (inter-quartile range)
    999 (999 to 999)
    999 (999 to 999)
    Notes
    [5] - For this analysis, the value of 999 indicates Not Estimable.
    [6] - For this analysis, the value of 999 indicates Not Estimable.
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.882
    Method
    Chi-squared
    Parameter type
    Cox proportional hazard
    Point estimate
    1.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.74
         upper limit
    1.41

    Secondary: The retention rate after 6 months comparing Levetiracetam versus the older Antiepileptic Drugs

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    End point title
    The retention rate after 6 months comparing Levetiracetam versus the older Antiepileptic Drugs
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 4 (approximately 26 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    841
    847
    Units: participants
        Number
    691
    677
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    1688
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.2422
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.157
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.906
         upper limit
    1.477

    Secondary: The retention rate after 12 months comparing Levetiracetam versus the older Antiepileptic Drugs

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    End point title
    The retention rate after 12 months comparing Levetiracetam versus the older Antiepileptic Drugs
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 5 (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    841
    847
    Units: participants
        number
    408
    380
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    1688
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.1402
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.155
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.954
         upper limit
    1.4

    Secondary: The retention rate after 6 months comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release

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    End point title
    The retention rate after 6 months comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 4 (approximately 26 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    492
    500
    Units: participants
        number
    402
    388
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    992
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.1229
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.277
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.936
         upper limit
    1.743

    Secondary: The retention rate after 6 months comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release

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    End point title
    The retention rate after 6 months comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 4 (approximately 26 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    349
    347
    Units: participants
        number
    289
    289
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.8269
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.957
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.643
         upper limit
    1.423

    Secondary: The retention rate after 12 months comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release

    Close Top of page
    End point title
    The retention rate after 12 months comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 5 (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    492
    500
    Units: participant
        number
    229
    203
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    992
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0725
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.979
         upper limit
    1.621

    Secondary: The retention rate after 12 months comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release

    Close Top of page
    End point title
    The retention rate after 12 months comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 5 (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    349
    347
    Units: participants
        number
    179
    177
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.9436
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.011
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.751
         upper limit
    1.361

    Secondary: Seizure freedom at 6 months comparing Levetiracetam versus older Antiepileptic Drugs

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    End point title
    Seizure freedom at 6 months comparing Levetiracetam versus older Antiepileptic Drugs
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 4 (approximately 26 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    841
    847
    Units: participants
        number
    431
    449
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    1688
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.4409
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.927
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.765
         upper limit
    1.124

    Secondary: Seizure freedom at 12 months comparing Levetiracetam versus older Antiepileptic Drugs

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    End point title
    Seizure freedom at 12 months comparing Levetiracetam versus older Antiepileptic Drugs
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 5 (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    841
    847
    Units: participants
        number
    238
    225
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    1688
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.4469
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.087
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.876
         upper limit
    1.349

    Secondary: Seizure freedom at 6 months comparing Levetiracetam versus older Antiepileptic Drugs based on based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release

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    End point title
    Seizure freedom at 6 months comparing Levetiracetam versus older Antiepileptic Drugs based on based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 4 (approximately 26 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    492
    500
    Units: participants
        number
    240
    244
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    992
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.9051
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.985
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.767
         upper limit
    1.265

    Secondary: Seizure freedom at 6 months comparing Levetiracetam versus older Antiepileptic Drugs based on based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release

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    End point title
    Seizure freedom at 6 months comparing Levetiracetam versus older Antiepileptic Drugs based on based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 4 (approximately 26 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    349
    347
    Units: participants
        number
    191
    205
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.2518
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.839
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.621
         upper limit
    1.133

    Secondary: Seizure freedom at 12 months comparing Levetiracetam versus older Antiepileptic Drugs based on based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release

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    End point title
    Seizure freedom at 12 months comparing Levetiracetam versus older Antiepileptic Drugs based on based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 5 (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    492
    500
    Units: participants
        number
    125
    108
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    992
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.1853
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.221
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.909
         upper limit
    1.64

    Secondary: Seizure freedom at 12 months comparing Levetiracetam versus older Antiepileptic Drugs based on based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release

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    End point title
    Seizure freedom at 12 months comparing Levetiracetam versus older Antiepileptic Drugs based on based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to Visit 5 (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    349
    347
    Units: participants
        number
    113
    117
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.7257
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.945
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.689
         upper limit
    1.296

    Secondary: Time to first seizure comparing Levetiracetam versus older Antiepileptic Drugs

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    End point title
    Time to first seizure comparing Levetiracetam versus older Antiepileptic Drugs
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to End of Study (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    841 [7]
    847 [8]
    Units: days
    median (inter-quartile range (Q1-Q3))
        median (inter-quartile range)
    999 (999 to 999)
    999 (999 to 999)
    Notes
    [7] - For this analysis, the value of 999 indicates Not Estimable.
    [8] - For this analysis, the value of 999 indicates Not Estimable.
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    1688
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.022
    Method
    Chi-squared
    Parameter type
    Cox proportional hazard
    Point estimate
    1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.03
         upper limit
    1.39

    Secondary: Time to first seizure comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release

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    End point title
    Time to first seizure comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to End of Study (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    492 [9]
    500 [10]
    Units: days
    median (inter-quartile range (Q1-Q3))
        median (inter-quartile range)
    999 (999 to 999)
    999 (999 to 999)
    Notes
    [9] - For this analysis, the value of 999 indicates Not Estimable.
    [10] - For this analysis, the value of 999 indicates Not Estimable.
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    992
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.061
    Method
    Chi-squared
    Parameter type
    Cox proportional hazard
    Point estimate
    1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.99
         upper limit
    1.46

    Secondary: Time to first seizure comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release

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    End point title
    Time to first seizure comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Sodium Valproate Extended Release
    End point description
    End point type
    Secondary
    End point timeframe
    Visit 1 to End of Study (approximately 52 weeks)
    End point values
    Levetiracetam Older Antiepileptic Drugs
    Number of subjects analysed
    349 [11]
    347 [12]
    Units: days
    median (inter-quartile range (Q1-Q3))
        median (inter-quartile range)
    999 (999 to 999)
    999 (999 to 999)
    Notes
    [11] - For this analysis, the value of 999 indicates Not Estimable.
    [12] - For this analysis, the value of 999 indicates Not Estimable.
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Levetiracetam v Older Antiepileptic Drugs
    Number of subjects included in analysis
    696
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.167
    Method
    Chi-squared
    Parameter type
    Cox proportional hazard
    Point estimate
    1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.93
         upper limit
    1.54

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent Adverse Events (TEAEs) were recorded during the study, which began in February 2005 and concluded in October 2007.
    Adverse event reporting additional description
    TEAES consists of the Intent-to-Treat (ITT) population group, which consists of all randomized subjects regardless of actual intake.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    9.0
    Reporting groups
    Reporting group title
    Older Antiepileptic Drugs
    Reporting group description
    Older AEDs consist of CBZ-CR 200 mg and 400 mg and VPA-ER 300 mg and 500 mg.

    Reporting group title
    Levetiracetam
    Reporting group description
    Daily dose of 1000 to 3000 mg film-coated oral tablets, 250-500 mg twice daily.

    Serious adverse events
    Older Antiepileptic Drugs Levetiracetam
    Total subjects affected by serious adverse events
         subjects affected / exposed
    61 / 841 (7.25%)
    106 / 835 (12.69%)
         number of deaths (all causes)
    3
    5
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 841 (0.12%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Cardiac operation
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess drainage
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder operation
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder neoplasm surgery
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hospitalisation
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Brain neoplasm
         subjects affected / exposed
    0 / 841 (0.00%)
    3 / 835 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebral haemangioma
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast neoplasm
         subjects affected / exposed
    1 / 841 (0.12%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Insulinoma
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mixed oligo-astrocytoma
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer stage III
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioma
         subjects affected / exposed
    2 / 841 (0.24%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 841 (0.12%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 841 (0.24%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sudden unexplained death in epilepsy
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Psychiatric disorders
    Abnormal behaviour
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 841 (0.12%)
    2 / 835 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychosomatic disease
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcoholism
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Restlessness
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somatoform disorder
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conversion disorder
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Menorrhagia
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    1 / 841 (0.12%)
    2 / 835 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Road traffic accident
         subjects affected / exposed
    0 / 841 (0.00%)
    2 / 835 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 841 (0.12%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body trauma
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus lesion
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation injury
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Skull fracture
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Concussion
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic brain injury
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug toxicity
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Body temperature increased
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Monocyte morphology abnormal
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    0 / 841 (0.00%)
    2 / 835 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 841 (0.12%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery disease
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Exomphalos
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous malformation
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Grand mal convulsion
         subjects affected / exposed
    2 / 841 (0.24%)
    6 / 835 (0.72%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    7 / 841 (0.83%)
    16 / 835 (1.92%)
         occurrences causally related to treatment / all
    3 / 8
    4 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    6 / 841 (0.71%)
    4 / 835 (0.48%)
         occurrences causally related to treatment / all
    1 / 6
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    1 / 841 (0.12%)
    4 / 835 (0.48%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures with secondary generalisation
         subjects affected / exposed
    1 / 841 (0.12%)
    3 / 835 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complex partial seizures
         subjects affected / exposed
    0 / 841 (0.00%)
    2 / 835 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    0 / 841 (0.00%)
    2 / 835 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Encephalitis
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 841 (0.12%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Simple partial seizures
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thalamic infarction
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope vasovagal
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIIIth nerve lesion
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    2 / 841 (0.24%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonic convulsion
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Eye disorders
    Retinal vein thrombosis
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heterophoria
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 841 (0.24%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 841 (0.24%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal impairment
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 841 (0.00%)
    2 / 835 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Generalised erythema
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 841 (0.12%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin haemorrhage
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 841 (0.00%)
    2 / 835 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle tightness
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (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
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Borrelia infection
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 841 (0.12%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    1 / 841 (0.12%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethritis
         subjects affected / exposed
    0 / 841 (0.00%)
    1 / 835 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 841 (0.24%)
    0 / 835 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Older Antiepileptic Drugs Levetiracetam
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    441 / 841 (52.44%)
    402 / 835 (48.14%)
    Investigations
    Weight increased
         subjects affected / exposed
    98 / 841 (11.65%)
    47 / 835 (5.63%)
         occurrences all number
    102
    47
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    70 / 841 (8.32%)
    68 / 835 (8.14%)
         occurrences all number
    89
    98
    Headache
         subjects affected / exposed
    170 / 841 (20.21%)
    161 / 835 (19.28%)
         occurrences all number
    335
    378
    Tremor
         subjects affected / exposed
    43 / 841 (5.11%)
    14 / 835 (1.68%)
         occurrences all number
    43
    14
    Somnolence
         subjects affected / exposed
    48 / 841 (5.71%)
    68 / 835 (8.14%)
         occurrences all number
    53
    83
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    134 / 841 (15.93%)
    120 / 835 (14.37%)
         occurrences all number
    156
    135
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    36 / 841 (4.28%)
    39 / 835 (4.67%)
         occurrences all number
    47
    53
    Psychiatric disorders
    Depression
         subjects affected / exposed
    20 / 841 (2.38%)
    42 / 835 (5.03%)
         occurrences all number
    24
    46
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    57 / 841 (6.78%)
    44 / 835 (5.27%)
         occurrences all number
    78
    56
    Diarrhoea
         subjects affected / exposed
    39 / 841 (4.64%)
    38 / 835 (4.55%)
         occurrences all number
    42
    48
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    23 / 841 (2.73%)
    11 / 835 (1.32%)
         occurrences all number
    23
    11
    Rash
         subjects affected / exposed
    28 / 841 (3.33%)
    8 / 835 (0.96%)
         occurrences all number
    29
    11
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    46 / 841 (5.47%)
    40 / 835 (4.79%)
         occurrences all number
    56
    65

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Dec 2005
    The purpose of the amendment was as follows: 1. To correct erroneous information such as the fax number of the Clinical Trial Manager. 2. To correct new staff functions. 3. To extend enrollment.
    29 Sep 2006
    This amendment introduced the collection of a new blood sample in order to retrieve pharmacogenomic data on SV2A. This data was to be collected in order to investigate the potential influence of specific polymorphisms in the protein on therapeutic response to LEV, CBZ-CR or VPA-ER. The analysis plan as well as the results of pharmacogenomic data are presented in this amended CSR.

    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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