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    Clinical Trial Results:
    A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients

    Summary
    EudraCT number
    		 2016-004952-30
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    12 Aug 2011

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Feb 2018
    First version publication date
    21 Feb 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    E2080-J081-304
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01146951
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Eisai Co., Ltd.
    Sponsor organisation address
    4-6-10 Koishikawa, Bunkyo-ku, Tokyo, Japan, 112-8088
    Public contact
    Customer Joy Department. EJ, Eisai Co., Ltd., Eisai Co., Ltd., 81(03) 3817-3700,
    Scientific contact
    Customer Joy Department. EJ, Eisai Co., Ltd., Eisai Co., Ltd., 81(03) 3817-3700,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Aug 2011
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Aug 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate that the efficacy of E2080 in percent change in tonic-atonic seizure frequency in participants with Lennox-Gastaut Syndrome (LGS) relative to placebo.
    Protection of trial subjects
    This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following: - Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008) - International Council on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312 - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states. - Article 14, Paragraph 3, and Article 80-2 of the Pharmaceutical Affairs Law (Law No. 145, 1960) for studies conducted in Japan, in addition to Japan’s GCP Subject Information and Informed Consent.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Jun 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Japan: 58
    Worldwide total number of subjects
    58
    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)
    23
    Adolescents (12-17 years)
    13
    Adults (18-64 years)
    22
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Of n= 66 who started Observation Period, 7 discontinued from study. Primary reasons were deviation of the inclusion/ exclusion criteria (n=5), untoward event before study treatment (n=1) & other (n=1). Of 59 participants, 58 were included in Full Analysis Set. 1 participant (E2080 group) was excluded due to inappropriate diagnosis of disease.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Rufinamide (E2080)
    Arm description
    		 Rufinamide : Rufinamide tablets administered orally twice daily after breakfast and dinner. Treatment was divided into a Dose Titration Period (2 weeks) and a Dose Maintenance Period (10 weeks). As a general rule, the dose was increased by 1 step every 2 days until it reached the target maintenance dose determined by body weight at the start of the Observation Period. Target maintenance dose: 15.0 - 30.0 kilograms (kg): 1000 milligrams/day (mg/day) (5 tablets each in the morning and evening) 30.1 - 50.0 kg: 1800 mg/day (4 tablets in the morning and 5 in the evening) 50.1 - 70.0 kg: 2400 mg/day (6 tablets each in the morning and evening) >= 70.1 kg: 3200 mg/day (8 tablets each in the morning and evening)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rufinamide
    Investigational medicinal product code
    E2080
    Other name
    Banzel
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Rufinamide tablets administered orally twice daily after breakfast and dinner. Treatment was divided into a Dose Titration Period (2 weeks) and a Dose Maintenance Period (10 weeks). As a general rule, the dose was increased by 1 step every 2 days until it reached the target maintenance dose determined by body weight at the start of the Observation Period. Target maintenance dose: 15.0 - 30.0 kg: 1000 mg/day (5 tablets each in the morning and evening) 30.1 - 50.0 kg: 1800 mg/day (4 tablets in the morning and 5 in the evening) 50.1 - 70.0 kg: 2400 mg/day (6 tablets each in the morning and evening) >= 70.1 kg: 3200 mg/day (8 tablets each in the morning and evening)

    Arm title
    		 Placebo
    Arm description
    		 Placebo : Rufinamide Matching Placebo tablets administered orally twice daily after breakfast and dinner for a total of 12 weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Rufinamide Matching Placebo tablets administered orally twice daily after breakfast and dinner for a total of 12 weeks.

    Number of subjects in period 1
    		Rufinamide (E2080) Placebo
    Started
    28
    30
    Completed
    24
    29
    Not completed
    4
    1
         Adverse event, non-fatal
    4
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Rufinamide (E2080)
    Reporting group description
    		 Rufinamide : Rufinamide tablets administered orally twice daily after breakfast and dinner. Treatment was divided into a Dose Titration Period (2 weeks) and a Dose Maintenance Period (10 weeks). As a general rule, the dose was increased by 1 step every 2 days until it reached the target maintenance dose determined by body weight at the start of the Observation Period. Target maintenance dose: 15.0 - 30.0 kilograms (kg): 1000 milligrams/day (mg/day) (5 tablets each in the morning and evening) 30.1 - 50.0 kg: 1800 mg/day (4 tablets in the morning and 5 in the evening) 50.1 - 70.0 kg: 2400 mg/day (6 tablets each in the morning and evening) >= 70.1 kg: 3200 mg/day (8 tablets each in the morning and evening)

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo : Rufinamide Matching Placebo tablets administered orally twice daily after breakfast and dinner for a total of 12 weeks

    Reporting group values
    		 Rufinamide (E2080) Placebo Total
    Number of subjects
    		 28 30 58
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 10 13 23
        Adolescents (12-17 years)
    		 6 7 13
        Adults (18-64 years)
    		 12 10 22
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    One participant from the Rufinamide (E2080) group was excluded from the Full Analysis Set because of the inappropriate diagnosis of the disease, dropping the total number from 29 to 28 participants.
    Units: years
        arithmetic mean (standard deviation)
    		 16 ( 7.1 ) 13.9 ( 6.1 ) -
    Gender categorical
    One subject from the Rufinamide (E2080) group was excluded from the FAS because of the inappropriate diagnosis of the disease, dropping the total number from 29 to 28 participants.
    Units: Subjects
        Female
    		 11 11 22
        Male
    		 17 19 36

    End points

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    End points reporting groups
    Reporting group title
    Rufinamide (E2080)
    Reporting group description
    		 Rufinamide : Rufinamide tablets administered orally twice daily after breakfast and dinner. Treatment was divided into a Dose Titration Period (2 weeks) and a Dose Maintenance Period (10 weeks). As a general rule, the dose was increased by 1 step every 2 days until it reached the target maintenance dose determined by body weight at the start of the Observation Period. Target maintenance dose: 15.0 - 30.0 kilograms (kg): 1000 milligrams/day (mg/day) (5 tablets each in the morning and evening) 30.1 - 50.0 kg: 1800 mg/day (4 tablets in the morning and 5 in the evening) 50.1 - 70.0 kg: 2400 mg/day (6 tablets each in the morning and evening) >= 70.1 kg: 3200 mg/day (8 tablets each in the morning and evening)

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo : Rufinamide Matching Placebo tablets administered orally twice daily after breakfast and dinner for a total of 12 weeks

    Primary: Percent Change in Tonic-Atonic Seizure Frequency from Baseline (Per 28 days)

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    End point title
    		 Percent Change in Tonic-Atonic Seizure Frequency from Baseline (Per 28 days)
    End point description
    The sum of the frequencies of tonic seizures and atonic seizures was defined as the “tonic-atonic seizure frequency”. The percent change in tonic-atonic seizure frequency per 28 days was assessed. The percent change in tonic-atonic seizure frequency was calculated using the tonic-atonic seizure frequency per 28 days of the Observation Period as the baseline and the tonic-atonic seizure frequency per 28 days of the Treatment Period as the post-treatment value. Percentage change in tonic-atonic seizure frequency was calculated as follows: [100 x (post-treatment value-baseline)/baseline]. The frequency of epileptic seizures was recorded in the seizure diary by the recorder. Seizure frequency was counted based on the classification established by the International League Against Epilepsy (ILAE). The diary recorder monitored the participant and recorded the seizure diary in a consistent manner, and continued these practices throughout the study period. Full Analysis Set (FAS) was analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (28 day observational period) and End of Treatment (28 day treatment period)
    End point values
    		 Rufinamide (E2080) Placebo
    Number of subjects analysed
    28
    30
    Units: Percent Change
        median (full range (min-max))
    -24.2 (-93.5 to 27.2)
    -3.25 (-81.6 to 151.9)
    Statistical analysis title
    		 Analysis of seizure frequecy
    Comparison groups
    Placebo v Rufinamide (E2080)
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Hodges–Lehmann
    Point estimate
    -26.65
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -40.3
         upper limit
    		 -11.8

    Secondary: Number of Participants achieving a 50% reduction in tonic-atonic

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    End point title
    		 Number of Participants achieving a 50% reduction in tonic-atonic
    End point description
    50% Responder Rate in Tonic-Atonic Seizure Frequency was presented as the number of participants who achieved a 50% reduction in tonic-atonic seizure frequency. FAS was defined as participants who were registered for the Treatment Period and excludes those listed below; Participants who did not meet the inclusion criterion related the target disease, participants who did not take the study drug, participants without any evaluable efficacy data after the start of study treatment.
    End point type
    Secondary
    End point timeframe
    12 weeks
    End point values
    		 Rufinamide (E2080) Placebo
    Number of subjects analysed
    28
    30
    Units: Participants
    number (not applicable)
        Yes (50% Reduction Achieved)
    7
    2
        No
    21
    28
    Statistical analysis title
    		 Analysis of 50% reduction in seizures
    Comparison groups
    Placebo v Rufinamide (E2080)
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.074
    Method
    		 Fisher exact
    Confidence interval

    Secondary: Percent Change in Total Seizure Frequency (Per 28 days)

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    End point title
    		 Percent Change in Total Seizure Frequency (Per 28 days)
    End point description
    Percent change in the total seizure frequency (per 28 days) was calculated using the total seizure frequency per 28 days of the Observation Period as the baseline and the total seizure frequency per 28 days of the Treatment Period as the post-treatment value. Percentage change in total seizure frequency was calculated as follows: [100 x (post-treatment value - baseline)/ baseline]. Full analysis set (FAS) is defined as participants who were registered for the Treatment Period and excludes those listed below. Participants who did not meet the inclusion criterion related the target disease, participants who did not take the study drug, participants without any evaluable efficacy data after the start of study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (28 day observational period) and End of Treatment (28 day treatment period)
    End point values
    		 Rufinamide (E2080) Placebo
    Number of subjects analysed
    28
    30
    Units: Percent Change
        median (full range (min-max))
    -32.9 (-87.3 to 15.4)
    -3.05 (-52.2 to 133)
    Statistical analysis title
    		 Analysis of total seizure frequency
    Comparison groups
    Rufinamide (E2080) v Placebo
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Hodges-Lehmann method
    Point estimate
    -33.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -47.1
         upper limit
    		 -17

    Secondary: Percentage change in the frequency of seizures other than tonic-atonic seizures (per 28 days)

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    End point title
    		 Percentage change in the frequency of seizures other than tonic-atonic seizures (per 28 days)
    End point description
    Percent change in the frequency of seizures other than tonic-atonic seizures (per 28 days) was calculated using the total seizure frequency per 28 days of the Observation Period as the baseline and the total seizure frequency per 28 days of the Treatment Period as the post-treatment value. Percentage change in total seizure frequency was calculated as follows: [100 x (post-treatment value - baseline)/ baseline]. Seizures analyzed other than tonic-atonic seizures included: Partial seizure freq. (frequency), Absence seizure, Atyp. (atypical) absence seizure, Myoclonic seizure, Clonic seizure, Tonic seizure, Tonic-clonic seizure, Atonic seizure, & Uncla. (unclassified) epileptic seizure. The frequency of epileptic seizures was recorded in the diary by the recorder. Seizure frequency was counted based on the classification established by the International League Against Epilepsy (ILAE). The diary recorder monitored the participant and recorded the seizure diary in a consistent manner.
    End point type
    Secondary
    End point timeframe
    Baseline (28 day observational period) and End of Treatment (28 day treatment period)
    End point values
    		 Rufinamide (E2080) Placebo
    Number of subjects analysed
    28
    30
    Units: Percent change
    median (full range (min-max))
        Partial Seizure Freq. % Change (n=4,6)
    -52.2 (-96.2 to -26.3)
    4.5 (-28.2 to 35.9)
        Absence Seizure Freq. % Change (n=1,0)
    3.4 (3.4 to 3.4)
    0 (0 to 0)
        Atyp. Absence Seizure Freq. % Change (n=12,19)
    -59 (-100 to 107.1)
    -21.1 (-83.2 to 253.5)
        Myoclonic Seizure Freq. % Change (n=10,10)
    -52.35 (-100 to 53.3)
    6.6 (-46.1 to 270)
        Clonic Seizure Freq. % Change (n=1,0)
    -81.2 (-81.2 to -81.2)
    0 (0 to 0)
        Tonic Seizure Freq. % Change (n=28,28)
    -24.2 (-92.6 to 42.8)
    -3.6 (-83.8 to 274.8)
        Tonic-clonic Seizure Freq. % Change (n=2,10)
    -57.35 (-100 to -14.7)
    2.35 (-75.8 to 450)
        Atonic Seizure Freq. % Change (n=10,12)
    -63.1 (-100 to 68.8)
    -6.1 (-100 to 2195.7)
        Uncla. Epileptic Seizure Freq. % Change (n=1,0)
    -88.7 (-88.7 to -88.7)
    0 (0 to 0)
    Statistical analysis title
    		 Analysis for Partial Seizure Frequency
    Comparison groups
    Rufinamide (E2080) v Placebo
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.025
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Hodges-Lehmann method
    Point estimate
    -57.15
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -104.5
         upper limit
    		 -17.3
    Statistical analysis title
    		 Analysis of atypical absence seizure frequency
    Comparison groups
    Placebo v Rufinamide (E2080)
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.128
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Hodges-Lehmann method
    Point estimate
    -28.65
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -72
         upper limit
    		 0.9
    Statistical analysis title
    		 Analysis for myoclonic seizure frequency
    Comparison groups
    Placebo v Rufinamide (E2080)
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.021
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Hodges-Lehmann method
    Point estimate
    -54.35
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -126.6
         upper limit
    		 -15.4
    Statistical analysis title
    		 Analysis of tonic seizure frequency
    Comparison groups
    Rufinamide (E2080) v Placebo
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.031
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Hodges-Lehmann method
    Point estimate
    -23.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -40.7
         upper limit
    		 -5.6
    Statistical analysis title
    		 Analysis for Tonic-clonic seizure frequency
    Comparison groups
    Placebo v Rufinamide (E2080)
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.107
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Hodges-Lehmann method
    Point estimate
    -71.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -464.7
         upper limit
    		 30.5
    Statistical analysis title
    		 Analysis of Atonic seizure frequency
    Comparison groups
    Placebo v Rufinamide (E2080)
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.221
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Hodges-Lehmann method
    Point estimate
    -52.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -89.1
         upper limit
    		 10.8

    Secondary: Clinical Global Impression of Change (CGIC)

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    End point title
    		 Clinical Global Impression of Change (CGIC)
    End point description
    CGIC in participants with Lennox-Gastaut Syndrome relative to placebo was presented as number of participants in each category at the final assessment (last observation carried forward [LOCF]) & at Week 12 of the Treatment Period. The investigator assessed the CGIC by comparing the participants' condition during the 4 weeks immediately before the completion (or discontinuation [d/c]) of the Treatment Period to his/her condition during the 4-week Observation Period (for participants who d/c'd the study during the Treatment Period, the CGIC was assessed by comparing the participant's condition from the start to discontinuation of the study treatment to his/her condition during the 4-week Observation Period). The CGIC was assessed according to the following 7-grade scale based on the frequency & severity of seizures, adverse events, and overall conditions of daily life. Markedly improved, Improved, Slightly improved, Unchanged, Slightly worsened, Worsened, Markedly worsened.
    End point type
    Secondary
    End point timeframe
    Up to Week 12 of the treatment period
    End point values
    		 Rufinamide (E2080) Placebo
    Number of subjects analysed
    28
    30
    Units: participants
    number (not applicable)
        Week 12: Markedly improved (n=25, 29)
    0
    0
        Week 12: Improved (n=25, 29)
    9
    0
        Week 12: Slightly Improved (n=25, 29)
    4
    9
        Week 12: Unchanged (n=25, 29)
    10
    18
        Week 12: Slightly Worsened (n=25, 29)
    1
    1
        Week 12: Worsened (n=25, 29)
    1
    1
        Week 12: Markedly Worsened (n=25, 29)
    0
    0
        LOCF: Markedly Improved (n=28, 30)
    3
    0
        LOCF: Improved (n=28, 30)
    9
    0
        LOCF: Slightly Improved (n=28, 30)
    4
    9
        LOCF: Unchanged (n=28, 30)
    10
    19
        LOCF: Slightly Worsened (n=28, 30)
    1
    1
        LOCF: Worsened (n=28, 30)
    1
    1
        LOCF: Markedly Worsened (n=28, 30)
    0
    0
    Statistical analysis title
    		 Analysis of Week 12 of the Treatment Period
    Comparison groups
    Rufinamide (E2080) v Placebo
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.041
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Analysis of final assessment (LOCF)
    Comparison groups
    Rufinamide (E2080) v Placebo
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.007
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From date of first dose until date of last dose of study treatment, up to approximately 1 year 2 months
    Adverse event reporting additional description
    Treatment-emergent adverse events and treatment-emergent serious adverse events were reported for the safety analysis set, which consisted of participants who registered for the Treatment Period and excludes participants who did not take study drug and those without any evaluable safety data after the start of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.0
    Reporting groups
    Reporting group title
    Rufinamide (E2080)
    Reporting group description
    		 Rufinamide tablets administered orally twice daily after breakfast and dinner. Treatment was divided into a Dose Titration Period (2 weeks) and a Dose Maintenance Period (10 weeks). As a general rule, the dose was increased by 1 step every 2 days until it reached the target maintenance dose determined by body weight at the start of the Observation Period. Target maintenance dose: 15.0 - 30.0 kg: 1000 mg/day (5 tablets each in the morning and evening) 30.1 - 50.0 kg: 1800 mg/day (4 tablets in the morning and 5 in the evening) 50.1 - 70.0 kg: 2400 mg/day (6 tablets each in the morning and evening) >= 70.1 kg: 3200 mg/day (8 tablets each in the morning and evening)

    Reporting group title
    Placebo
    Reporting group description
    		 Rufinamide Matching Placebo tablets administered orally twice daily after breakfast and dinner for a total of 12 weeks.

    Serious adverse events
    		 Rufinamide (E2080) Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 30 (3.33%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Skin and subcutaneous tissue disorders
    Drug eruption
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Rufinamide (E2080) Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 29 (93.10%)
    21 / 30 (70.00%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Rhinorrhoea
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Stereotypy
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Blood Lactate Dehydrogenase Increased
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Blood Pressure Decreased
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Blood Pressure Increased
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 30 (3.33%)
         occurrences all number
    1
    2
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Lymphocyte Count Decreased
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Platelet Count Decreased
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Excoriation
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Eye injury
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Subcutaneous Haematoma
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Tooth injury
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Nervous system disorders
    Autism
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Dizziness
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Complex partial seizures
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Psychomotor Hyperactivity
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Somnolence
         subjects affected / exposed
    6 / 29 (20.69%)
    2 / 30 (6.67%)
         occurrences all number
    6
    2
    Status Epilepticus
         subjects affected / exposed
    8 / 29 (27.59%)
    5 / 30 (16.67%)
         occurrences all number
    9
    9
    Tonic Convulsion
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Anal Fissure
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Aphthous Stomatitis
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Dental Caries
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Gingival Bleeding
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Vomiting
         subjects affected / exposed
    5 / 29 (17.24%)
    1 / 30 (3.33%)
         occurrences all number
    7
    1
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Eczema
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Purpura
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Skin chapped
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Heat rash
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Hyperkeratosis
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Drug eruption
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Joint Swelling
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Cellulitis
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    9 / 29 (31.03%)
    9 / 30 (30.00%)
         occurrences all number
    10
    9
    Otitis Media
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Rhinitis
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Upper Respiratory Tract Infection
         subjects affected / exposed
    2 / 29 (6.90%)
    4 / 30 (13.33%)
         occurrences all number
    2
    4
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    6 / 29 (20.69%)
    2 / 30 (6.67%)
         occurrences all number
    6
    2
    Dehydration
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 May 2010
    • Description of the method for examining concomitant drugs was modified. • Date and time of taking E2080 and concomitant AEDs immediately before blood sampling for plasma drug concentration measurements were deleted from the monitoring procedure. • Explanation to the investigator and sub investigator was added.
    05 Jul 2010
    • Check for blinding of the study drug before packaging the study drug by the allocation manager was deleted. • The study implementation structure of the sponsor and the responsible person were changed. • Matters to be described in the CRF (postponement of dose increase or reduction, and increase in the interval of tapering) were deleted from the identification of the source data.
    13 Oct 2010
    • Phenobarbital (suppository) was added to rescue drugs for status epilepticus. • The study implementation structure of the sponsor was changed. • Monitors were changed. • Responsible persons at the case registration center, emergency key code control center, and clinical research organization were changed.
    11 Apr 2011
    • The study implementation structure of the sponsor was changed.

    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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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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