Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Double-blind, Randomized, Placebo-controlled, Multicenter, Parallel-group Study with an Open-label Extension Phase to Evaluate the Efficacy and Safety of Adjunctive Perampanel in Primary Generalized Tonic-Clonic Seizures

    Summary
    EudraCT number
    		 2011-000265-12
    Trial protocol
    		 HU   DE   LV   GR   AT   CZ   NL   PL   LT  
    Global end of trial date
    13 Nov 2015

    Results information
    Results version number
    		 v1
    This version publication date
    22 Jun 2016
    First version publication date
    22 Jun 2016
    Other versions
    		 v2

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    E2007-G000-332
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01393743
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Eisai
    Sponsor organisation address
    100 Tice Boulevard, Woodcliff Lake, United States, 07677
    Public contact
    Medical Information, Eisai Limited, 44 2086001400, LMedInfo@eisai.net
    Scientific contact
    Medical Information, Eisai Limited, 44 2086001400, LMedInfo@eisai.net
    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
    13 Nov 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 May 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Nov 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the efficacy of adjunctive perampanel therapy, compared to placebo, on primary generalized tonic-clonic (PGTC) seizures
    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 Conference 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 Conference on Harmonisation 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
    13 Jul 2011
    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
    Poland: 6
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    Czech Republic: 5
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Greece: 2
    Country: Number of subjects enrolled
    Latvia: 8
    Country: Number of subjects enrolled
    Lithuania: 4
    Country: Number of subjects enrolled
    Australia: 17
    Country: Number of subjects enrolled
    China: 36
    Country: Number of subjects enrolled
    India: 13
    Country: Number of subjects enrolled
    Israel: 3
    Country: Number of subjects enrolled
    Japan: 11
    Country: Number of subjects enrolled
    Korea, Republic of: 7
    Country: Number of subjects enrolled
    Serbia: 2
    Country: Number of subjects enrolled
    United States: 39
    Worldwide total number of subjects
    163
    EEA total number of subjects
    35
    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)
    22
    Adults (18-64 years)
    140
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Out of 138 participants who entered the extension phase, 78 participants completed and 60 participants discontinued the extension phase. Reasons for participant discontinuation was as follows: adverse event (12); lost to follow-up (2); participant choice (16); lack of efficacy (7); withdrawal of consent (8); pregnancy (1); and not specified (14).

    Pre-assignment
    Screening details
    		 Of the 307 participants who were screened, 143 participants were screen failures and 164 participants were eligible to continue in the study but 1 participant withdrew from the perampanel group prior to receiving treatment.

    Period 1
    Period 1 title
    Core Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    Everyone in the Core Study took a total of 6 tablets of study drug, (combination of placebo alone or active drug plus placebo) in order to maintain the blind during the open-label Extension Blinded Conversion Period, which allowed participants to titrate a total daily dose of 12 mg (2 mg x 6 tablets). Participants whose dose was reduced due to intolerable adverse events was allocated a different kit that contained more placebo tablets in order to maintain the same total number of tablets (n=6).

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo (Core Study)
    Arm description
    		 Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.
    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
    Participants received 6 tablets of perampanel-matched placebo, once a day, before bedtime and with food.

    Arm title
    		 Perampanel (Core Study)
    Arm description
    		 Participants received 6 tablets (initially,1 tablet of 2 mg perampanel plus 5 tablets of perampanel matched placebo) and up-titrated weekly in 2 mg increments to a target dose range of 8 mg per day maintaining the blind with administration of 6 tablets per day of either perampanel/perampanel matched placebo.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Perampanel
    Investigational medicinal product code
    E2007
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received 6 tablets (initially ,1 tablet of 2 mg perampanel plus 5 tablets of perampanel matched placebo) and up-titrated weekly in 2 mg increments to a target dose range of 8 mg per day maintaining the blind with administration of 6 tablets per day of either perampanel/perampanel matched placebo.

    Number of subjects in period 1
    		Placebo (Core Study) Perampanel (Core Study)
    Started
    82
    81
    Completed
    72
    68
    Not completed
    10
    13
         Adverse event, non-fatal
    5
    9
         Participant's choice
    2
    3
         Lost to follow-up
    1
    1
         Inadequate therapeutic effect
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo (Core Study)
    Reporting group description
    		 Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.

    Reporting group title
    Perampanel (Core Study)
    Reporting group description
    		 Participants received 6 tablets (initially,1 tablet of 2 mg perampanel plus 5 tablets of perampanel matched placebo) and up-titrated weekly in 2 mg increments to a target dose range of 8 mg per day maintaining the blind with administration of 6 tablets per day of either perampanel/perampanel matched placebo.

    Reporting group values
    		 Placebo (Core Study) Perampanel (Core Study) Total
    Number of subjects
    		 82 81 163
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    The full analysis set included all randomized participants who received at least 1 dose of study drug and had any postbaseline seizure frequency data.
    Units: years
        median (full range (min-max))
    		 26 (14 to 70) 26 (12 to 58) -
    Gender categorical
    Units: Subjects
        Female
    		 46 46 92
        Male
    		 36 35 71
    Subject analysis sets

    Subject analysis set title
    Perampanel Extension Phase
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Eligible participants from the Core Study had the option of entering into the Extension Phase. A total of 138 participants entered into the Extension Phase, 70 participants from the placebo arm of the Core Study and 68 participants from the perampanel arm of the Core Study. The Extension Phase Full Analysis Set (FAS) included all participants who were eligible to participate in the Extension Phase, received at least 1 dose of study drug in this phase, and had baseline seizure frequency data and at least 1 observation of valid seizure diary data during study drug treatment duration.

    Subject analysis set title
    Perampanel Extension Phase PGTC Seizures
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The median percent change from the Pre-perampanel baseline in PGTC seizure frequency per 28 days by 13-week intervals through greater than or equal to Week 144.

    Subject analysis set title
    Perampanel Extension Phase All Seizures
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The median percent change from the Pre-perampanel baseline in the seizure frequency per 28 days of all seizures by 13-week intervals through greater than or equal to Week 144.

    Subject analysis sets values
    		 Perampanel Extension Phase Perampanel Extension Phase PGTC Seizures Perampanel Extension Phase All Seizures
    Number of subjects
    138
    138
    138
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    The full analysis set included all randomized participants who received at least 1 dose of study drug and had any postbaseline seizure frequency data.
    Units: years
        median (full range (min-max))
    25 (12 to 70)
    Gender categorical
    Units: Subjects
        Female
        Male

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo (Core Study)
    Reporting group description
    		 Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.

    Reporting group title
    Perampanel (Core Study)
    Reporting group description
    		 Participants received 6 tablets (initially,1 tablet of 2 mg perampanel plus 5 tablets of perampanel matched placebo) and up-titrated weekly in 2 mg increments to a target dose range of 8 mg per day maintaining the blind with administration of 6 tablets per day of either perampanel/perampanel matched placebo.

    Subject analysis set title
    Perampanel Extension Phase
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Eligible participants from the Core Study had the option of entering into the Extension Phase. A total of 138 participants entered into the Extension Phase, 70 participants from the placebo arm of the Core Study and 68 participants from the perampanel arm of the Core Study. The Extension Phase Full Analysis Set (FAS) included all participants who were eligible to participate in the Extension Phase, received at least 1 dose of study drug in this phase, and had baseline seizure frequency data and at least 1 observation of valid seizure diary data during study drug treatment duration.

    Subject analysis set title
    Perampanel Extension Phase PGTC Seizures
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The median percent change from the Pre-perampanel baseline in PGTC seizure frequency per 28 days by 13-week intervals through greater than or equal to Week 144.

    Subject analysis set title
    Perampanel Extension Phase All Seizures
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The median percent change from the Pre-perampanel baseline in the seizure frequency per 28 days of all seizures by 13-week intervals through greater than or equal to Week 144.

    Primary: Median Percent Change in Primary Generalized Tonic Clonic Seizure Frequency (PGTC) Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study)

    		 Close Top of page
    End point title
    		 Median Percent Change in Primary Generalized Tonic Clonic Seizure Frequency (PGTC) Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study)
    End point description
    Seizure frequency per 28 days was derived from the information recorded in the participant diaries. PGTC seizure frequency per 28 days (as determined from participant diaries) was calculated as the number of PGTC seizures divided by the number of days in the interval and multiplied by 28. The percent change from baseline in PGTC seizure was analyzed over the Titration and Maintenance Periods combined, while baseline was defined as seizure frequency per 28 days based on all valid diary data during the Prerandomization Phase.
    End point type
    Primary
    End point timeframe
    Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)
    End point values
    		 Placebo (Core Study) Perampanel (Core Study)
    Number of subjects analysed
    81
    81
    Units: Percent change
        median (full range (min-max))
    -38.38 (-100 to 1546.3)
    -76.47 (-100 to 184.5)
    Statistical analysis title
    		 Median Difference to Placebo
    Statistical analysis description
    The median difference to placebo and the 95% confidence interval are based on the Hodges-Lehmann method.
    Comparison groups
    Placebo (Core Study) v Perampanel (Core Study)
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [1]
    Method
    		 ANCOVA
    Parameter type
    		 Median difference (final values)
    Point estimate
    -30.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -45.49
         upper limit
    		 -15.244
    Notes
    [1] - The P-value is based on a rank analysis of covariance with treatment and pooled country as factors, and prerandomization seizure frequency as a covariate.

    Primary: 50% Responder Rate for Primary Generalized Tonic Clonic Seizure During Maintenance-LOCF - (for Core Study)

    		 Close Top of page
    End point title
    		 50% Responder Rate for Primary Generalized Tonic Clonic Seizure During Maintenance-LOCF - (for Core Study)
    End point description
    A responder was a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance-last observation carried forward (LOCF) from prerandomization. The data was presented as the percentage of participants.
    End point type
    Primary
    End point timeframe
    Baseline (4 or 8 weeks) and Maintenance (13 weeks)
    End point values
    		 Placebo (Core Study) Perampanel (Core Study)
    Number of subjects analysed
    81
    81
    Units: Percentage of participants
        number (not applicable)
    39.5
    64.2
    Statistical analysis title
    		 P Value Compared to Placebo
    Statistical analysis description
    The P value is based on non-missing values and is from a Cochran-Mantel-Haenszel test stratified by pooled country.
    Comparison groups
    Perampanel (Core Study) v Placebo (Core Study)
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0019
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Primary: 50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency per 28 days Relative to the Core Study Prerandomization Phase – (for Extension Phase)

    		 Close Top of page
    End point title
    		 50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency per 28 days Relative to the Core Study Prerandomization Phase – (for Extension Phase) [2]
    End point description
    Responder rate was defined as the percentage of participants who experienced a 50% or greater reduction in PGTC and total seizure frequency during treatment per 28 days relative to baseline (responder). Week 1 began on the date of first dose of the perampanel treatment regardless of whether it occurred in the Core Study or Extension Phase and continued to and included the date of the last dose of perampanel in the Extension Phase. For any given analysis window and seizure type(s), a 50% response from Core Study Prerandomization is a participant whose seizure frequency per 28 days for that seizure type(s) during that analysis window is 50% to 100% lower than his or her Core Study Prerandomization baseline seizure frequency per 28 days for that same seizure type(s). In Part B of the Extension Phase (after Visit 15), the seizure diary is only completed for days on which a seizure occurred and missing days were imputed as non-seizure days.
    End point type
    Primary
    End point timeframe
    Week 1 of perampanel treatment to date of last dose of perampanel in the Extension Phase
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistics were not calculated for this endpoint.
    End point values
    		 Perampanel Extension Phase
    Number of subjects analysed
    138
    Units: Percentage of participants
    number (not applicable)
        Core Study Maintenance Period
    55.1
        Extension Conversion Period
    74.6
        Extension Phase Maintenance Period Weeks 1 to 13
    75.9
        Extension Phase Maintenance Period Weeks 14 to 26
    78.4
        Extension Phase Maintenance Period Weeks 27 to 39
    78.1
        Extension Phase Maintenance Period Weeks 40 to 52
    79.8
        Extension Phase Maintenance Period Weeks 53 to 65
    81.8
        Extension Phase Maintenance Period Weeks 66 to 78
    76.5
        Extension Phase Maintenance Period Weeks 79 to 91
    80.3
        Extension Phase Maintenance Period Weeks 92 to 104
    91.4
    No statistical analyses for this end point

    Secondary: 50% Responder Rate for All Seizures During Maintenance-LOCF - (for Core Study)

    		 Close Top of page
    End point title
    		 50% Responder Rate for All Seizures During Maintenance-LOCF - (for Core Study)
    End point description
    All seizures included PGTC, myoclonic, absence and all other seizures that occur during the study. A responder was a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance- LOCF from prerandomization. The data was presented as percentage of participants.
    End point type
    Secondary
    End point timeframe
    Baseline (4 or 8 weeks) and Maintenance (13 weeks)
    End point values
    		 Placebo (Core Study) Perampanel (Core Study)
    Number of subjects analysed
    81
    81
    Units: Percentage of participants
        number (not applicable)
    34.6
    45.7
    Statistical analysis title
    		 P value compared to placebo
    Statistical analysis description
    The P value is based on non-missing values and is from a Cochran-Mantel-Haenszel test stratified by pooled country.
    Comparison groups
    Placebo (Core Study) v Perampanel (Core Study)
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1826
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Median Percent Change in all Seizure Frequency per 28 days during the Titration and Maintenance Periods (combined) Relative to Baseline (Prerandomization) - (for Core Study)

    		 Close Top of page
    End point title
    		 Median Percent Change in all Seizure Frequency per 28 days during the Titration and Maintenance Periods (combined) Relative to Baseline (Prerandomization) - (for Core Study)
    End point description
    Seizure frequency per 28 days was derived from the information recorded in the participant diaries. PGTC seizure frequency per 28 days was calculated as the number of PGTC seizures divided by the number of days in the interval and multiplied by 28. The percent change in seizure frequency relative to baseline (prerandomization) for all seizures (PGTC, myoclonic, absence and all other seizures that occur during the study) per 28 days during the Titration and Maintenance Periods combined was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)
    End point values
    		 Placebo (Core Study) Perampanel (Core Study)
    Number of subjects analysed
    81
    81
    Units: Percent Change
        median (full range (min-max))
    -22.87 (-100 to 125.7)
    -43.4 (-100 to 1366.7)
    Statistical analysis title
    		 Median Difference to Placebo
    Statistical analysis description
    The median difference to placebo and the 95% confidence interval are based on the Hodges-Lehmann method.
    Comparison groups
    Perampanel (Core Study) v Placebo (Core Study)
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0018 [3]
    Method
    		 ANCOVA
    Parameter type
    		 Median difference (final values)
    Point estimate
    -23.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -40.668
         upper limit
    		 -8.518
    Notes
    [3] - The P value is based on a rank analysis of covariance with treatment and pooled country as factors, and prerandomization seizure frequency as a covariate.

    Secondary: Median Percent Change in Primary Generalized Seizure Subtype Frequency per 28 days during the Titration and Maintenance Periods (combined) Relative to Baseline (Prerandomization) - (for Core Study)

    		 Close Top of page
    End point title
    		 Median Percent Change in Primary Generalized Seizure Subtype Frequency per 28 days during the Titration and Maintenance Periods (combined) Relative to Baseline (Prerandomization) - (for Core Study)
    End point description
    Seizure frequency per 28 days was derived from the information recorded in the participant diaries. PGTC seizure frequency per 28 days was calculated as the number of PGTC seizures divided by the number of days in the interval and multiplied by 28. The percent change in seizure frequency relative to baseline (prerandomization) for primary generalized seizure subtype (myoclonic and absence) per 28 days during the Titration and Maintenance Periods combined was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)
    End point values
    		 Placebo (Core Study) Perampanel (Core Study)
    Number of subjects analysed
    81
    81
    Units: Percent Change
    median (full range (min-max))
        Absence
    -7.58 (-100 to 592.4)
    -41.18 (-100 to 8088.2)
        Myoclonic
    -52.54 (-100 to 321.2)
    -24.47 (-100 to 482.4)
    Statistical analysis title
    		 Median Difference to Placebo for Absence Seizures
    Statistical analysis description
    The median difference to placebo and the 95% confidence interval are based on the Hodges-Lehmann method.
    Comparison groups
    Placebo (Core Study) v Perampanel (Core Study)
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3478 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Median difference (final values)
    Point estimate
    -12.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -53.054
         upper limit
    		 26.989
    Notes
    [4] - The P value is based on a rank analysis of covariance with treatment and pooled country as factors, and prerandomization seizure frequency as a covariate.
    Statistical analysis title
    		 Median Difference to Placebo for Myoclonic Seizure
    Statistical analysis description
    The median difference to placebo and the 95% confidence interval are based on the Hodges-Lehmann method.
    Comparison groups
    Placebo (Core Study) v Perampanel (Core Study)
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.61
    Method
    		 ANCOVA
    Parameter type
    		 Median difference (final values)
    Point estimate
    24.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.338
         upper limit
    		 59.938

    Secondary: 50% Responder Rate for Primary Generalized Seizure Subtype During Maintenance - LOCF - (for Core Study)

    		 Close Top of page
    End point title
    		 50% Responder Rate for Primary Generalized Seizure Subtype During Maintenance - LOCF - (for Core Study)
    End point description
    Primary generalized seizure subtype included absence and myoclonic seizures. A responder was a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance - (last observation carried forward LOCF) from prerandomization. The data was presented as the percentage of participants.
    End point type
    Secondary
    End point timeframe
    Baseline (4 or 8 weeks) and Maintenance (13 weeks)
    End point values
    		 Placebo (Core Study) Perampanel (Core Study)
    Number of subjects analysed
    81
    81
    Units: Percentage of participants
    number (not applicable)
        Absence
    39.4
    48.1
        Myoclonic
    60.9
    41.7
    Statistical analysis title
    		 P Value Compared to Placebo for Absence Seizures
    Statistical analysis description
    The P value is based on non-missing values and is from a Cochran-Mantel-Haenszel test stratified by pooled country.
    Comparison groups
    Placebo (Core Study) v Perampanel (Core Study)
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4653
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 P Value Compared to Placebo for Myoclonic Seizures
    Statistical analysis description
    The P value is based on non-missing values and is from a Cochran-Mantel-Haenszel test stratified by pooled country.
    Comparison groups
    Placebo (Core Study) v Perampanel (Core Study)
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3694
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percent Change from Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency per 28 Days - (for Extension Phase)

    		 Close Top of page
    End point title
    		 Percent Change from Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency per 28 Days - (for Extension Phase)
    End point description
    Week 1 began on the date of first dose of the perampanel treatment regardless of whether it occurred in the Core Study or Extension Phase and continued to and included the date of the last dose of perampanel in the Extension Phase. For any given analysis window and seizure type(s), a 50% responder from Core Study Randomization is a participant whose seizure frequency per 28 days for that seizure type(s) during that analysis window is 50% to 100% lower than his or her Core Study Prerandomization baseline seizure frequency per 28 days for that same seizure type(s). In Part B of the Extension Phase (after Visit 15), the seizure diary is only completed for days on which a seizure occurred and missing days were imputed as non-seizure days.
    End point type
    Secondary
    End point timeframe
    Date of first dose of study drug to date of last dose of study drug in the Extension Phase
    End point values
    		 Perampanel Extension Phase
    Number of subjects analysed
    138
    Units: Percent change in PGTC seizure frequency
    median (full range (min-max))
        Core Study Titration Period
    -57.72 (-100 to 500)
        Core Study Maintenance Period
    -57.4 (-100 to 2011.6)
        Extension Phase Conversion Period
    -100 (-100 to 166.7)
        Extension Phase Maintenance Period, Weeks 1 to 13
    -84.62 (-100 to 594.5)
        Extension Phase Maintenance Period, Weeks 14 to 26
    -86.81 (-100 to 186.2)
        Extension Phase Maintenance Period, Weeks 27 to 39
    -86.62 (-100 to 250.8)
        Extension Phase Maintenance Period, Weeks 40 to 52
    -100 (-100 to 146.2)
        Extension Phase Maintenance Period, Weeks 53 to 65
    -100 (-100 to 150.5)
        Extension Phase Maintenance Period, Weeks 66 to 78
    -100 (-100 to 108.8)
        Extension Phase Maintenance, Weeks 79 to 91
    -100 (-100 to 140.1)
        Extension Phase Maintenance, Weeks 92 to 104
    -100 (-100 to 171.4)
    No statistical analyses for this end point

    Secondary: Summary of Percent Change from Pre-Perampanel Baseline in Seizure Frequency per 28 Days - (for Extension Phase)

    		 Close Top of page
    End point title
    		 Summary of Percent Change from Pre-Perampanel Baseline in Seizure Frequency per 28 Days - (for Extension Phase)
    End point description
    Efficacy assessments included seizure counts from participant diaries. The percent change in seizure frequency was assessed during the perampanel treatment duration, with the pre-perampanel baseline being used for evaluating the change. The pre-perampanel baseline was defined as follows: 1) for all participants who had been assigned to placebo treatment in the Core Study, the pre-perampanel baseline was computed from all valid seizure diary data during the Core Study, and 2) for participants who had been assigned to perampanel in the Core Study, the pre-perampanel baseline was computed from all valid seizure diary data during the Prerandomization Phase plus the 4 weeks prior to the Prerandomization Phase of the Core Study. The perampanel treatment duration consisted of: 1) the Randomization Phase of the Core Study plus the Extension Phase for participants assigned to perampanel in the Core Study, and 2) the Extension Phase for participants assigned to placebo in the Core Study.
    End point type
    Secondary
    End point timeframe
    Weeks: 1 to 13, 14 to 26, 27 to 39, 40 to 52, 53 to 65, 66 to 78, 79 to 91, 92 to 104, 105 to 117, 118 to 130, 131 to 143, greater than or equal to 144
    End point values
    		 Perampanel Extension Phase PGTC Seizures Perampanel Extension Phase All Seizures
    Number of subjects analysed
    138
    138
    Units: Median Percent Change
    number (not applicable)
        Weeks 1 - 13 (n = 138)
    -77.45
    -56.54
        Weeks 14 - 26 (n = 133)
    -74.21
    -63.53
        Weeks 27 - 39 (n = 125)
    -84.62
    -79.49
        Weeks 40 - 52 (n = 118)
    -89.65
    -83.38
        Weeks 53 - 65 (n = 109)
    -92.45
    -83.33
        Weeks 66 - 78 (n = 90)
    -100
    -88.71
        Weeks 79 - 91 (n = 80)
    -100
    -90.28
        Weeks 92 - 104 (n = 52)
    -100
    -98.96
        Weeks 105 - 117 (n = 41)
    -100
    -96.42
        Weeks 118 - 130 (n = 27)
    -100
    -96.58
        Weeks 131 - 143 (n = 19)
    -100
    -91.7
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment Emergent Adverse events and serious adverse events as a measure of safety and tolerability of perampanel in subjects with inadequately controlled PGTC seizures - (for Core Study)

    		 Close Top of page
    End point title
    		 Number of Participants with Treatment Emergent Adverse events and serious adverse events as a measure of safety and tolerability of perampanel in subjects with inadequately controlled PGTC seizures - (for Core Study)
    End point description
    An Adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered an investigational product. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening (i.e., the subject was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect (in the child of a subject who was exposed to the study drug). In this study, treatment emergent adverse events (TEAEs) (defined as an AE that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) were assessed.
    End point type
    Secondary
    End point timeframe
    For each participant, from the first treatment dose till 30 days after the last dose or up to 21 weeks for core study and 142 weeks for extension phase.
    End point values
    		 Placebo (Core Study) Perampanel (Core Study)
    Number of subjects analysed
    82
    81
    Units: Participants
    number (not applicable)
        Treatment emergent adverse events
    59
    67
        Treatment emergent serious adverse events
    7
    6
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the date of first dose of perampanel up to 30 days after the last dose, or up to approximately 163 weeks total.
    Adverse event reporting additional description
    Treatment-emergent Adverse Events (TEAEs) included AEs that occurred from the first dose of perampanel (in Core Study or Extension Phase) to 30 days after the last dose of perampanel, or that were present before the first day of perampanel administration but worsened in severity during the study. TEAEs are reported in the Safety Section.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Placebo (Core Study)
    Reporting group description
    		 Participants received 6 tablets of perampanel matched placebo, once a day.

    Reporting group title
    Perampanel (Core Study)
    Reporting group description
    		 Participants received 6 tablets (initially ,1 tablet of 2 mg perampanel plus 5 tablets of perampanel matched placebo) and up-titrated weekly in 2 mg increments to a target dose range of 8 mg per day maintaining the blind with administration of 6 tablets per day of either perampanel/perampanel matched placebo.

    Reporting group title
    Perampanel (Extension Phase)
    Reporting group description
    		 The Extension Phase had two parts: Part A (6-week blinded Conversion Period plus a 32-week Maintenance Period) and Part B (maximum of 104-week Maintenance Period). Part A: Participants who received placebo in the Core Study were started on blinded oral perampanel (2 mg/day) and were up-titrated weekly in 2-mg increments to the optimal dose per investigator's discretion. Participants who were assigned to the perampanel arm in the Core Study continued to receive blinded perampanel once daily at the dose received during the Maintenance Period of the Core Study. Conversion Period: dose adjustments could be made at the investigator’s discretion. Part B: Participants were unblinded to study treatment and remained on the optimal perampanel dose established during the blinded Conversion Period (Part A). Dose adjustment in 2-mg increments (upwards or downwards) was allowed at the investigator's discretion. The maximum dose of perampanel allowed during the Extension Phase was 12 mg/day.

    Serious adverse events
    		 Placebo (Core Study) Perampanel (Core Study) Perampanel (Extension Phase)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 82 (8.54%)
    6 / 81 (7.41%)
    18 / 138 (13.04%)
         number of deaths (all causes)
    1
    1
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Endometrial adenocarcinoma
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous incomplete
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Drowning
         subjects affected / exposed
    0 / 82 (0.00%)
    1 / 81 (1.23%)
    0 / 138 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Reproductive system and breast disorders
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicidal ideation
         subjects affected / exposed
    0 / 82 (0.00%)
    1 / 81 (1.23%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 82 (0.00%)
    1 / 81 (1.23%)
    2 / 138 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aggression
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric symptom
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychogenic seizure
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 82 (1.22%)
    0 / 81 (0.00%)
    0 / 138 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    1 / 82 (1.22%)
    0 / 81 (0.00%)
    0 / 138 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    2 / 82 (2.44%)
    1 / 81 (1.23%)
    3 / 138 (2.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Grand Mal Convulsion
         subjects affected / exposed
    1 / 82 (1.22%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Status eiplepticus
         subjects affected / exposed
    1 / 82 (1.22%)
    1 / 81 (1.23%)
    0 / 138 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sedation
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 82 (0.00%)
    1 / 81 (1.23%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 82 (1.22%)
    0 / 81 (0.00%)
    0 / 138 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Hepatobiliary disorders
    Cholecystitis chronic
         subjects affected / exposed
    0 / 82 (0.00%)
    1 / 81 (1.23%)
    0 / 138 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Invertebral disc protrusion
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 81 (0.00%)
    1 / 138 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo (Core Study) Perampanel (Core Study) Perampanel (Extension Phase)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    36 / 82 (43.90%)
    56 / 81 (69.14%)
    106 / 138 (76.81%)
    Investigations
    Weight increased
         subjects affected / exposed
    3 / 82 (3.66%)
    6 / 81 (7.41%)
    13 / 138 (9.42%)
         occurrences all number
    3
    7
    14
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    3 / 82 (3.66%)
    5 / 81 (6.17%)
    12 / 138 (8.70%)
         occurrences all number
    3
    5
    15
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 82 (6.10%)
    26 / 81 (32.10%)
    53 / 138 (38.41%)
         occurrences all number
    5
    26
    64
    Headache
         subjects affected / exposed
    8 / 82 (9.76%)
    10 / 81 (12.35%)
    17 / 138 (12.32%)
         occurrences all number
    10
    19
    61
    Somnolence
         subjects affected / exposed
    3 / 82 (3.66%)
    9 / 81 (11.11%)
    18 / 138 (13.04%)
         occurrences all number
    3
    11
    22
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    5 / 82 (6.10%)
    12 / 81 (14.81%)
    14 / 138 (10.14%)
         occurrences all number
    5
    12
    16
    Irritability
         subjects affected / exposed
    2 / 82 (2.44%)
    9 / 81 (11.11%)
    19 / 138 (13.77%)
         occurrences all number
    2
    9
    24
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 82 (2.44%)
    7 / 81 (8.64%)
    15 / 138 (10.87%)
         occurrences all number
    5
    7
    19
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    3 / 82 (3.66%)
    5 / 81 (6.17%)
    11 / 138 (7.97%)
         occurrences all number
    3
    5
    12
    Vomiting
         subjects affected / exposed
    2 / 82 (2.44%)
    7 / 81 (8.64%)
    9 / 138 (6.52%)
         occurrences all number
    2
    10
    16
    Abdominal pain
         subjects affected / exposed
    1 / 82 (1.22%)
    4 / 81 (4.94%)
    8 / 138 (5.80%)
         occurrences all number
    1
    4
    8
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    3 / 82 (3.66%)
    4 / 81 (4.94%)
    7 / 138 (5.07%)
         occurrences all number
    3
    4
    8
    Insomnia
         subjects affected / exposed
    4 / 82 (4.88%)
    3 / 81 (3.70%)
    12 / 138 (8.70%)
         occurrences all number
    4
    3
    17
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    7 / 82 (8.54%)
    7 / 81 (8.64%)
    20 / 138 (14.49%)
         occurrences all number
    8
    7
    31
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 82 (6.10%)
    4 / 81 (4.94%)
    18 / 138 (13.04%)
         occurrences all number
    7
    5
    25

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Oct 2011
    • Clarified age level per health authority request to postpone recruitment of adolescent subjects until safety data are available from the ongoing pediatric study. • Evidence of active hepatic disease was added as an exclusion criterion per health authority request. • The Conversion Period was extended to eliminate potential unblinding. • Increased the number of PGTC seizures (from ≥2 to ≥3) required during the 8-week Baseline Period. • Added prohibited medications to exclusion criteria to meet health authority requirements.
    12 Apr 2012
    • Study duration was extended by 52 weeks to provide subjects the option to continue accessing perampanel treatment if they are benefiting from the study drug; Extension Phase was split into Part A and Part B. • To guarantee uninterrupted treatment to those subjects who benefit from perampanel, stipulated treatment until perampanel became commercially available. • Increased the maximum number of AEDs allowed to 3 to align with patient population targeted by this protocol, based on feedback from Key Opinion Leaders. • Exclusion of subjects aged ≥65 years for India per the request of the Drug Controller General of India. • Increased the number of sites changed to 95 to ensure target recruitment was met in a timely fashion. • Addition of QOLIE-31-P and HCRU to demonstrate that improving the seizure frequency impacts quality of life of these subjects, including visits to hospitals.
    15 Nov 2013
    • Extension Phase Part B extended by 52 weeks to provide continued treatment until efficacy and safety results in this indication become available. • Specified an end of treatment visit for subjects who had at least 52 weeks of treatment in the Extension Phase. • Stipulated explicitly, the termination of the Extension Phase upon commercial availability of perampanel or if a positive risk-benefit assessment in this indication was not demonstrated. • Added decision points for subjects’ continued participation after completion of Extension Part A. As an added safety measure a total of 52 weeks exposure to perampanel was to be achieved before extended treatment is initiated.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    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.

    European Medicines Agency © 1995-Sun Apr 28 21:15:32 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA