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    Clinical Trial Results:
    A Double-blind Trial Comparing the Efficacy, Tolerability and Safety of Monotherapy Topiramate Versus Phenytoin in Subjects With Seizures Indicative of New Onset Epilepsy

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    		 2015-001222-42
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    06 Aug 2007

    Results information
    Results version number
    		 v2(current)
    This version publication date
    15 Jul 2016
    First version publication date
    31 Jul 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Review of data

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CAPSS-272
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00210782
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Johnson & Johnson Pharmaceutical Research and Development
    Sponsor organisation address
    Archimedesweg 29, Leiden, Netherlands, 2333CM
    Public contact
    Clinical Registry Group-JB BV, Johnson & Johnson Pharmaceutical Research and Development, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group-JB BV, Johnson & Johnson Pharmaceutical Research and Development, ClinicalTrialsEU@its.jnj.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
    06 Aug 2007
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Aug 2007
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study was to compare the effectiveness and safety of two treatment regimens, topiramate as compared to phenytoin, in preventing seizures in subjects with new-onset epilepsy who require rapid initiation of antiepileptic drug therapy. The purpose of the Open-Label Extension Phase of the study was to evaluate the efficacy, tolerability, and safety of monotherapy topiramate during the 12-week Open-Label Extension Phase in subjects who completed the Double-Blind Phase of the study or who exited the Double-Blind Phase of the study due to seizure.
    Protection of trial subjects
    Safety evaluations for this study included monitoring of adverse events, clinical laboratory tests (hematology, serum chemistry and urinalysis), vital sign measurements, physical and neurological examination.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Jun 2004
    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
    United States: 261
    Worldwide total number of subjects
    261
    EEA total number of subjects
    0
    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)
    29
    Adults (18-64 years)
    221
    From 65 to 84 years
    11
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Of the 261 subjects who were randomized into the study 133 subjects received topiramate and 128 received phenytoin. Overall, 217 subjects (83.1%) completed the Double-Blind Phase of the study.

    Period 1
    Period 1 title
    Baseline Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Topiramate
    Arm description
    		 The initiation dose on Day 1 for topiramate-randomized subjects was 100 milligram (mg), administered orally as an initial dose of 50 mg of topiramate, followed by two successive doses of 25 mg each administered at 2-hour intervals.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TOPAMAX
    Investigational medicinal product code
    Other name
    TOPIRAMATE
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The initiation dose on Day 1 for topiramate-randomized subjects was 100 milligram (mg), administered orally as an initial dose of 50 mg of topiramate, followed by two successive doses of 25 mg each administered at 2-hour intervals.

    Arm title
    		 Phenytoin
    Arm description
    		 The initiation dose on Day 1 for phenytoin-randomized subjects was 1,000 mg, administered orally as an initial dose of 400 mg of phenytoin, followed by two successive doses of 300 mg each administered at 2-hour intervals.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    PHENYTEK
    Investigational medicinal product code
    Other name
    PHENYTOIN SODIUM
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The initiation dose on Day 1 for phenytoin-randomized subjects was 1,000 mg, administered orally as an initial dose of 400 mg of phenytoin, followed by two successive doses of 300 mg each administered at 2-hour intervals.

    Number of subjects in period 1
    		Topiramate Phenytoin
    Started
    128
    126
    Completed
    128
    126
    Period 2
    Period 2 title
    Double Blind
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Topiramate
    Arm description
    		 The initiation dose on Day 1 for topiramate-randomized subjects was 100 milligram (mg), administered orally as an initial dose of 50 mg of topiramate, followed by two successive doses of 25 mg each administered at 2-hour intervals.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TOPAMAX
    Investigational medicinal product code
    Other name
    TOPIRAMATE
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The initiation dose on Day 1 for topiramate-randomized subjects was 100 milligram (mg), administered orally as an initial dose of 50 mg of topiramate, followed by two successive doses of 25 mg each administered at 2-hour intervals.

    Arm title
    		 Phenytoin
    Arm description
    		 The initiation dose on Day 1 for phenytoin-randomized subjects was 1,000 mg, administered orally as an initial dose of 400 mg of phenytoin, followed by two successive doses of 300 mg each administered at 2-hour intervals.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    PHENYTEK
    Investigational medicinal product code
    Other name
    PHENYTOIN SODIUM
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The initiation dose on Day 1 for phenytoin-randomized subjects was 1,000 mg, administered orally as an initial dose of 400 mg of phenytoin, followed by two successive doses of 300 mg each administered at 2-hour intervals.

    Number of subjects in period 2
    		Topiramate Phenytoin
    Started
    133
    128
    Completed
    116
    101
    Not completed
    17
    27
         Consent withdrawn by subject
    4
    2
         Adverse event, non-fatal
    7
    14
         Other
    3
    7
         Adverse event, serious
    1
    2
         Lost to follow-up
    2
    2

    Baseline characteristics

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    Baseline characteristics reporting groups [1]
    Reporting group title
    Topiramate
    Reporting group description
    		 The initiation dose on Day 1 for topiramate-randomized subjects was 100 milligram (mg), administered orally as an initial dose of 50 mg of topiramate, followed by two successive doses of 25 mg each administered at 2-hour intervals.

    Reporting group title
    Phenytoin
    Reporting group description
    		 The initiation dose on Day 1 for phenytoin-randomized subjects was 1,000 mg, administered orally as an initial dose of 400 mg of phenytoin, followed by two successive doses of 300 mg each administered at 2-hour intervals.

    Notes
    [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Not all the enrolled subjects were treated with study drugs. As baseline only included treated subjects, the worldwide number enrolled in the trial differs with the number of subjects reported in the baseline period
    Reporting group values
    		 Topiramate Phenytoin Total
    Number of subjects
    		 128 126 254
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 15 14 29
        Adults (18-64 years)
    		 109 105 214
        From 65 to 84 years
    		 4 7 11
        85 years and over
    		 0 0 0
    Title for AgeContinuous
    Units: Years
        arithmetic mean (standard deviation)
    		 33.3 ± 14.2 35.1 ± 15.37 -
    Title for Gender
    Units: subjects
        Female
    		 78 55 133
        Male
    		 50 71 121
    Subject analysis sets

    Subject analysis set title
    Double Blind ITT (Intent-to-treat) Analysis Set - Topiramate
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    ITT Population is defined as all randomized subjects who received at least one dose of study drug and had at least one post-randomization efficacy measurement.

    Subject analysis set title
    Double Blind ITT (Intent-to-treat) Analysis Set - Phenytoin
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    ITT Population is defined as all randomized subjects who received at least one dose of study drug and had at least one post-randomization efficacy measurement.

    Subject analysis sets values
    		 Double Blind ITT (Intent-to-treat) Analysis Set - Topiramate Double Blind ITT (Intent-to-treat) Analysis Set - Phenytoin
    Number of subjects
    128
    126
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    15
    14
        Adults (18-64 years)
    109
    105
        From 65 to 84 years
    4
    7
        85 years and over
    0
    0
    Title for AgeContinuous
    Units: Years
        arithmetic mean (standard deviation)
    33.3 ± 14.2
    35.1 ± 15.37
    Title for Gender
    Units: subjects
        Female
    78
    55
        Male
    50
    71

    End points

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    End points reporting groups
    Reporting group title
    Topiramate
    Reporting group description
    		 The initiation dose on Day 1 for topiramate-randomized subjects was 100 milligram (mg), administered orally as an initial dose of 50 mg of topiramate, followed by two successive doses of 25 mg each administered at 2-hour intervals.

    Reporting group title
    Phenytoin
    Reporting group description
    		 The initiation dose on Day 1 for phenytoin-randomized subjects was 1,000 mg, administered orally as an initial dose of 400 mg of phenytoin, followed by two successive doses of 300 mg each administered at 2-hour intervals.
    Reporting group title
    Topiramate
    Reporting group description
    		 The initiation dose on Day 1 for topiramate-randomized subjects was 100 milligram (mg), administered orally as an initial dose of 50 mg of topiramate, followed by two successive doses of 25 mg each administered at 2-hour intervals.

    Reporting group title
    Phenytoin
    Reporting group description
    		 The initiation dose on Day 1 for phenytoin-randomized subjects was 1,000 mg, administered orally as an initial dose of 400 mg of phenytoin, followed by two successive doses of 300 mg each administered at 2-hour intervals.

    Subject analysis set title
    Double Blind ITT (Intent-to-treat) Analysis Set - Topiramate
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    ITT Population is defined as all randomized subjects who received at least one dose of study drug and had at least one post-randomization efficacy measurement.

    Subject analysis set title
    Double Blind ITT (Intent-to-treat) Analysis Set - Phenytoin
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    ITT Population is defined as all randomized subjects who received at least one dose of study drug and had at least one post-randomization efficacy measurement.

    Primary: Time to First Seizure During The Double Blind Phase

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    End point title
    		 Time to First Seizure During The Double Blind Phase
    End point description
    Efficacy analysis set included all ITT subjects who received at least 1 dose of study drug and had at least 1 post-randomization efficacy measurement.
    End point type
    Primary
    End point timeframe
    Day 1 up to Day 28
    End point values
    		 Topiramate Phenytoin
    Number of subjects analysed
    128
    126
    Units: days
        arithmetic mean (standard error)
    25.4 ± 0.61
    24.8 ± 0.44
    Statistical analysis title
    		 Wald Chi square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with time to first seizure.
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.3661
    Method
    		 Wald Chi-squared
    Confidence interval

    Secondary: Effect of sex, age, Baseline Weight, Baseline Seizure Type, and Duration Since First Diagnosis of Epilepsy on the Time to Seizure

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    End point title
    		 Effect of sex, age, Baseline Weight, Baseline Seizure Type, and Duration Since First Diagnosis of Epilepsy on the Time to Seizure
    End point description
    Efficacy analysis set included all ITT subjects who received at least 1 dose of study drug and had at least 1 post-randomization efficacy measurement. No descriptive data was planned to be analyzed for this endpoint. Thus NA (Not applicable)= +/-9999
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 28
    End point values
    		 Topiramate Phenytoin
    Number of subjects analysed
    128
    126
    Units: ratio
    arithmetic mean (standard error)
        Effect of Sex
    -99999 ± 99999
    -99999 ± 99999
        Effect of Age
    -99999 ± 99999
    -99999 ± 99999
        Effect of Baseline Weight
    -99999 ± 99999
    -99999 ± 99999
        Effect of Generalized Tonic-Clonic Seizures
    -99999 ± 99999
    -99999 ± 99999
        Effect of Complex Partial Seizure
    -99999 ± 99999
    -99999 ± 99999
        Effect of Simple Partial Seizure
    -99999 ± 99999
    -99999 ± 99999
        Effect of Absence Seizures
    -99999 ± 99999
    -99999 ± 99999
        Effect of Myoclonic Seizures
    -99999 ± 99999
    -99999 ± 99999
        Effect of Other Seizures
    -99999 ± 99999
    -99999 ± 99999
        Duration Since First Diagnosis of Epilepsy
    -99999 ± 99999
    -99999 ± 99999
    Statistical analysis title
    		 Statistical Analysis 1: Wald Chi square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with sex.
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.8021
    Method
    		 Wald Chi-squared
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 2: Wald Chi square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with age.
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.7616
    Method
    		 Wald Chi-squared
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 3: Wald Chi square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with baseline weight
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.5147
    Method
    		 Wald Chi-squared
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 4: Wald Chi square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with generalized tonic-clonic seizure.
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.9353
    Method
    		 Wald Chi-squared
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 5: Wald Chi Square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with complex partial seizure.
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.063
    Method
    		 Wald Chi-squared
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 6: Wald Chi Square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with simple partial seizure.
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.7094
    Method
    		 Wald Chi-square
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 7: Wald Chi Square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with absence seizure.
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.9899
    Method
    		 Wald Chi-squared
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 8: Wald Chi Square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with myoclonic seizure.
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.5001
    Method
    		 Wald Chi-squared
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 9: Wald Chi Square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with other seizure type.
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.9947
    Method
    		 Wald Chi-squared
    Confidence interval
    Statistical analysis title
    		 Statistical Analysis 10: Wald Chi Square
    Statistical analysis description
    Inferential Tests for treatment difference in time to first seizure by exiting seizure type during the double-blind phase was analyzed using Wald test from Cox proportional hazard model with duration since first diagnosis of epilepsy on the time to seizure.
    Comparison groups
    Topiramate v Phenytoin
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.7131
    Method
    		 Wald Chi-squared
    Confidence interval

    Secondary: Proportion of Subjects who Were Seizure-Free at Day 28

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    End point title
    		 Proportion of Subjects who Were Seizure-Free at Day 28
    End point description
    Efficacy analysis set included all ITT subjects who received at least 1 dose of study drug and had at least 1 post-randomization efficacy measurement.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    		 Topiramate Phenytoin
    Number of subjects analysed
    128
    126
    Units: subjects
    92
    87
    No statistical analyses for this end point

    Secondary: Time to First Seizure by Seizure Type

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    End point title
    		 Time to First Seizure by Seizure Type
    End point description
    Time to first seizure by seizure type was calculated Kaplan-Meier estimates for the ITT Population for each treatment group. Efficacy analysis set included all ITT subjects who received at least 1 dose of study drug and had at least 1 post-randomization efficacy measurement.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 28
    End point values
    		 Topiramate Phenytoin
    Number of subjects analysed
    128
    126
    Units: days
    arithmetic mean (standard error)
        Time to First Generalized Tonic-Clonic Seizure
    24.3 ± 0.34
    25.9 ± 0.1
        Time to First Complex Partial Seizure
    26.3 ± 0.52
    23.9 ± 0.42
    No statistical analyses for this end point

    Secondary: Incidence of Seizures Observed During the Double Blind Phase

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    End point title
    		 Incidence of Seizures Observed During the Double Blind Phase
    End point description
    The proportion of subjects who experienced GTC or complex partial seizures, GTC seizures, complex partial seizures and seizures of all types were observed during the double blind phase of the study. Efficacy analysis set included all ITT subjects who received at least 1 dose of study drug and had at least 1 post-randomization efficacy measurement.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 28
    End point values
    		 Topiramate Phenytoin
    Number of subjects analysed
    128
    126
    Units: Number
    arithmetic mean (standard deviation)
        GTC or Complex Partial Seizures
    0.4 ± 1.3
    0.2 ± 0.8
        Generalized tonic-clonic seizures
    0.1 ± 0.56
    0.1 ± 0.29
        Complex Partial Seizures
    0.3 ± 1.21
    0.2 ± 0.75
        Seizures of all Types
    0.5 ± 1.33
    0.3 ± 0.87
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 up to Day 49
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 WHOART
    Dictionary version
    1992
    Reporting groups
    Reporting group title
    Topiramate
    Reporting group description
    		 Topiramate

    Reporting group title
    Phenytoin
    Reporting group description
    		 Phenytoin

    Serious adverse events
    		 Topiramate Phenytoin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 132 (1.52%)
    5 / 127 (3.94%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Cerebrovascular Disorder
         subjects affected / exposed
    0 / 132 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac Failure
         subjects affected / exposed
    0 / 132 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsions Grand Mal
         subjects affected / exposed
    1 / 132 (0.76%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 132 (0.00%)
    1 / 127 (0.79%)
         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
    Syncope
         subjects affected / exposed
    1 / 132 (0.76%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 132 (0.00%)
    2 / 127 (1.57%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide Attempt
         subjects affected / exposed
    0 / 132 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Topiramate Phenytoin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    77 / 132 (58.33%)
    72 / 127 (56.69%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    26 / 132 (19.70%)
    35 / 127 (27.56%)
         occurrences all number
    34
    36
    Paraesthesia
         subjects affected / exposed
    29 / 132 (21.97%)
    5 / 127 (3.94%)
         occurrences all number
    37
    5
    Headache
         subjects affected / exposed
    11 / 132 (8.33%)
    15 / 127 (11.81%)
         occurrences all number
    14
    17
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    12 / 132 (9.09%)
    11 / 127 (8.66%)
         occurrences all number
    12
    12
    Eye disorders
    Vision Abnormal
         subjects affected / exposed
    6 / 132 (4.55%)
    9 / 127 (7.09%)
         occurrences all number
    6
    10
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    9 / 132 (6.82%)
    12 / 127 (9.45%)
         occurrences all number
    9
    14
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 132 (0.76%)
    9 / 127 (7.09%)
         occurrences all number
    1
    9
    Psychiatric disorders
    Confusion
         subjects affected / exposed
    8 / 132 (6.06%)
    2 / 127 (1.57%)
         occurrences all number
    8
    3
    Somnolence
         subjects affected / exposed
    16 / 132 (12.12%)
    18 / 127 (14.17%)
         occurrences all number
    19
    19
    Difficulty with Concentration/Attention
         subjects affected / exposed
    8 / 132 (6.06%)
    3 / 127 (2.36%)
         occurrences all number
    8
    3
    Nervousness
         subjects affected / exposed
    7 / 132 (5.30%)
    2 / 127 (1.57%)
         occurrences all number
    8
    2
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    9 / 132 (6.82%)
    7 / 127 (5.51%)
         occurrences all number
    9
    7

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Jun 2005
    Amendment 1 provided specific criteria for acceptable benzodiazepine use, added text specifying visit windows, and provided details about follow-up for subjects who exited due to a complex partial or GTC seizure, about taper for subjects not entering the Open-Label Extension Phase, and about returned study drug.
    31 May 2006
    Amendment 2 included the following changes: Change in the primary analysis model, allowing a decrease in the sample size from 310 subjects (155 per treatment group) to 262 subjects (131 per treatment group); change in primary efficacy analysis for the Double-Blind Phase from Kaplan-Meier estimates of the cumulative rate of time to the first seizure to a non-inferiority log-rank test for the equivalence of 2 seizure-free survival curves; allow subjects with a positive tetrahydrocannabinol (THC) at screening to enter the study, establishment of independent data monitoring committee (IDMC), procedure to allow subjects to receive a prescription for topiramate at the end of the Open-Label Extension Phase, since topiramate had been approved for monotherapy.

    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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