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    Clinical Trial Results:
    A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial With an Open-Label Extension Phase of Perampanel as Adjunctive Treatment in Subjects at Least 2 Years of Age With Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome

    Summary
    EudraCT number
    		 2014-002321-35
    Trial protocol
    		 HU   BE   LV   PL   CZ   FR   IT  
    Global end of trial date
    19 Jul 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Jan 2022
    First version publication date
    29 Jan 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    E2007-G000-338
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02834793
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Eisai Ltd.
    Sponsor organisation address
    European Knowledge Centre, Mosquito Way, Hatfield, Hertfordshire, United Kingdom, AL10 9SN
    Public contact
    Eisai Medical Information, Eisai Ltd., 44 845 676 1400, EUMedInfo@eisai.net
    Scientific contact
    Eisai Medical Information, Eisai Ltd., 44 845 676 1400, EUMedInfo@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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Jul 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Jul 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to demonstrate that perampanel given as adjunctive antiepileptic treatment was superior compared to placebo in reducing the incidence of drop seizures during 18 weeks of treatment in subjects with inadequately controlled seizures associated with Lennox-Gastaut Syndrome (LGS).
    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 - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country, and Title 21 of the United States Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and IRB regulations and applicable sections of US 21 CFR Part 312. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Dec 2016
    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
    Australia: 4
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    Czechia: 1
    Country: Number of subjects enrolled
    Japan: 19
    Country: Number of subjects enrolled
    Korea, Republic of: 4
    Country: Number of subjects enrolled
    United States: 35
    Worldwide total number of subjects
    70
    EEA total number of subjects
    8
    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)
    35
    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
    		 Subjects took part in the study at 40 investigative sites in Australia, Belgium, the Czech Republic, Japan, India, South Korea, and the United States from 13 December 2016 to 19 July 2021. A total of 101 subjects were enrolled (signed informed consent) and 70 subjects were randomized to receive study treatment in Core Study.

    Pre-assignment
    Screening details
    		 This study included a Core Study Phase and an Extension Phase, which in turn consisted of Extension A and Extension B. Study was terminated early by the sponsor due to recruitment challenges that was further impacted by the COVID-19 pandemic.

    Period 1
    Period 1 title
    Core Study (Up to 18 Weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Core Study: Placebo
    Arm description
    		 Subjects received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension (formulation was selected based on the subject’s condition and at the discretion of the investigator), once daily at bedtime during the titration period. During the maintenance period, subjects continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study was 18 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo matched to perampanel oral suspension
    Investigational medicinal product code
    Other name
    E2007
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to perampanel oral suspension, once daily at bedtime during Titration Period for up to 6 weeks. During the Maintenance Period, subjects continued to receive the placebo matched to perampanel oral suspension dose level that was administered at the end of the Titration Period for up to 12 weeks.

    Investigational medicinal product name
    Placebo matched to perampanel tablet
    Investigational medicinal product code
    Other name
    E2007
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to perampanel 2 mg, oral tablet, once daily at bedtime during Titration Period for up to 6 weeks. During the Maintenance Period, subjects continued to receive the placebo matched to perampanel tablet at dose level that was administered at the end of the Titration Period for up to 12 weeks.

    Arm title
    		 Core Study: Perampanel
    Arm description
    		 Subjects received starting dose of perampanel, one 2 milligram (mg) oral tablet or 4 milliliter (mL) oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 milligram per day (mg/day) during titration period. During the maintenance period, subjects continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study was 18 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Perampanel oral suspension
    Investigational medicinal product code
    Other name
    E2007
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received starting dose of perampanel 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime then up-titrated in 2-mg increments to a target dose of 8 mg/day during Titration Period for up to 6 weeks. During the Maintenance Period, subjects continued to receive the perampanel dose level that was administered at the end of the Titration Period for up to 12 weeks.

    Investigational medicinal product name
    Perampanel oral tablet
    Investigational medicinal product code
    Other name
    E2007
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received starting dose of perampanel, 2 mg, oral tablet, once daily at bedtime then up-titrated in 2-mg increments to a target dose of 8 milligram per day (mg/day) during Titration Period for up to 6 weeks. During the Maintenance Period, subjects continued to receive the perampanel dose level that was administered at the end of the Titration Period for up to 12 weeks.

    Number of subjects in period 1
    		Core Study: Placebo Core Study: Perampanel
    Started
    36
    34
    Completed
    32
    29
    Not completed
    4
    5
         Consent withdrawn by subject
    1
    1
         Adverse event, non-fatal
    -
    3
         Subject Choice
    1
    -
         Study terminated by sponsor
    -
    1
         Lost to follow-up
    1
    -
         Lack of efficacy
    1
    -
    Period 2
    Period 2 title
    Extension Phase A (up to 52 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Extension Phase A: Perampanel
    Arm description
    		 Subjects who completed the Core Study and who were eligible entered into Extension Phase A. Subjects previously assigned to perampanel arm (Core Study) continued taking study medication at the dose received during the Core maintenance period, and subjects previously assigned to a placebo arm (Core Study) started perampanel dose as one 2 mg tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to a maximum dose of 8 mg/day for 6 weeks conversion period of Extension Phase A. After the conversion period, subjects could be titrated up to 12 mg/day in 2-week intervals during the maintenance period (46 weeks) of Extension Phase A as per the investigator’s discretion. The total duration of the conversion period and maintenance period in Extension Phase A was 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Perampanel oral suspension
    Investigational medicinal product code
    Other name
    E2007
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    During Extension Phase A conversion period, subjects previously assigned to a placebo arm (in Core Study) received perampanel 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated in 2 mg increments to a target dose of 8 mg/day, and subjects previously assigned to perampanel arm (Core Study) continued taking study medication at the dose received during the Core Maintenance Period. After the 6 weeks conversion period, subjects could be titrated up to 12 mg/day in 2-week intervals during the Maintenance Period (up to 46 weeks) of Extension Phase A.

    Investigational medicinal product name
    Perampanel oral tablet
    Investigational medicinal product code
    Other name
    E2007
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    During Extension Phase A conversion period, subjects previously assigned to a placebo arm (in Core Study) received perampanel, 2 mg, oral tablet, once daily at bedtime then up-titrated in 2 mg increments to a target dose of 8 milligram per day (mg/day), and subjects previously assigned to perampanel arm (Core Study) continued taking study medication at the dose received during the Core Maintenance Period. After the 6 weeks conversion period, subjects could be titrated up to 12 mg/day in 2-week intervals during the Maintenance Period (up to 46 weeks) of Extension Phase A.

    Number of subjects in period 2 [1]
    		Extension Phase A: Perampanel
    Started
    58
    Completed
    32
    Not completed
    26
         Consent withdrawn by subject
    4
         Adverse event, non-fatal
    5
         Subject Choice
    3
         Not Specified
    1
         Study terminated by sponsor
    9
         Lack of efficacy
    4
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Subjects who completed the Core Study had the option to roll over into Extension Phase A.
    Period 3
    Period 3 title
    Extension Phase B (up to 188 Weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Extension Phase B: Perampanel
    Arm description
    		 Subjects who completed Extension Phase A and who were eligible entered into Extension Phase B. Subjects received perampanel at their optimal perampanel dose (that is, dose maintained at the end of Extension A) until perampanel was available commercially or accessible via extended access program (EAP) (in the country in which a subject resides) or unless study termination by the sponsor (up to 188 weeks).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Perampanel oral suspension
    Investigational medicinal product code
    Other name
    E2007
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received perampanel, oral suspension at their optimal dose (that is, dose maintained at the end of Extension A) up to 188 weeks.

    Investigational medicinal product name
    Perampanel oral tablet
    Investigational medicinal product code
    Other name
    E2007
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received perampanel tablet, orally at their optimal dose (that is, dose maintained at the end of Extension A) up to 188 weeks.

    Number of subjects in period 3 [2]
    		Extension Phase B: Perampanel
    Started
    13
    Completed
    1
    Not completed
    12
         Adverse event, non-fatal
    1
         Subject Choice
    1
         Not Specified
    1
         Study terminated by sponsor
    8
         Lack of efficacy
    1
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Subjects who completed Extension Phase A and who were eligible entered into Extension Phase B.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Core Study: Placebo
    Reporting group description
    		 Subjects received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension (formulation was selected based on the subject’s condition and at the discretion of the investigator), once daily at bedtime during the titration period. During the maintenance period, subjects continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study was 18 weeks.

    Reporting group title
    Core Study: Perampanel
    Reporting group description
    		 Subjects received starting dose of perampanel, one 2 milligram (mg) oral tablet or 4 milliliter (mL) oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 milligram per day (mg/day) during titration period. During the maintenance period, subjects continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study was 18 weeks.

    Reporting group values
    		 Core Study: Placebo Core Study: Perampanel Total
    Number of subjects
    		 36 34 70
    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)
    		 19 16 35
        Adolescents (12-17 years)
    		 7 6 13
        Adults (18-64 years)
    		 10 12 22
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 13.3 ( 7.80 ) 14.7 ( 10.37 ) -
    Sex: Female, Male
    Units: subjects
        Female
    		 13 17 30
        Male
    		 23 17 40
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 13 13 26
        Native Hawaiian or Other Pacific Islander
    		 1 0 1
        Black or African American
    		 4 2 6
        White
    		 15 16 31
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 3 3 6
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 5 4 9
        Not Hispanic or Latino
    		 31 30 61
        Unknown or Not Reported
    		 0 0 0
    Subject analysis sets

    Subject analysis set title
    Extension Phase: Perampanel
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects who completed Core Study entered Extension A. Subjects who received perampanel in Core Study, continued at dose received during Core maintenance period, and subjects who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, subjects could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator’s discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Subjects who completed Extension A had option to enter into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose(dose at end of Extension A) until perampanel was available commercially or unless study termination(up to 188 weeks).

    Subject analysis sets values
    		 Extension Phase: Perampanel
    Number of subjects
    58
    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)
    30
        Adolescents (12-17 years)
    10
        Adults (18-64 years)
    18
        From 65-84 years
    0
        85 years and over
    0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    13.3 ( 8.17 )
    Sex: Female, Male
    Units: subjects
        Female
    24
        Male
    34
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
        Asian
    23
        Native Hawaiian or Other Pacific Islander
    1
        Black or African American
    5
        White
    24
        More than one race
    0
        Unknown or Not Reported
    5
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    6
        Not Hispanic or Latino
    52
        Unknown or Not Reported
    0

    End points

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    End points reporting groups
    Reporting group title
    Core Study: Placebo
    Reporting group description
    		 Subjects received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension (formulation was selected based on the subject’s condition and at the discretion of the investigator), once daily at bedtime during the titration period. During the maintenance period, subjects continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study was 18 weeks.

    Reporting group title
    Core Study: Perampanel
    Reporting group description
    		 Subjects received starting dose of perampanel, one 2 milligram (mg) oral tablet or 4 milliliter (mL) oral suspension (containing 2 mg perampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 milligram per day (mg/day) during titration period. During the maintenance period, subjects continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study was 18 weeks.
    Reporting group title
    Extension Phase A: Perampanel
    Reporting group description
    		 Subjects who completed the Core Study and who were eligible entered into Extension Phase A. Subjects previously assigned to perampanel arm (Core Study) continued taking study medication at the dose received during the Core maintenance period, and subjects previously assigned to a placebo arm (Core Study) started perampanel dose as one 2 mg tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to a maximum dose of 8 mg/day for 6 weeks conversion period of Extension Phase A. After the conversion period, subjects could be titrated up to 12 mg/day in 2-week intervals during the maintenance period (46 weeks) of Extension Phase A as per the investigator’s discretion. The total duration of the conversion period and maintenance period in Extension Phase A was 52 weeks.
    Reporting group title
    Extension Phase B: Perampanel
    Reporting group description
    		 Subjects who completed Extension Phase A and who were eligible entered into Extension Phase B. Subjects received perampanel at their optimal perampanel dose (that is, dose maintained at the end of Extension A) until perampanel was available commercially or accessible via extended access program (EAP) (in the country in which a subject resides) or unless study termination by the sponsor (up to 188 weeks).

    Subject analysis set title
    Extension Phase: Perampanel
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects who completed Core Study entered Extension A. Subjects who received perampanel in Core Study, continued at dose received during Core maintenance period, and subjects who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2-mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, subjects could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator’s discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Subjects who completed Extension A had option to enter into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose(dose at end of Extension A) until perampanel was available commercially or unless study termination(up to 188 weeks).

    Primary: Core Study: Median Percent Change in Drop Seizure Frequency per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)

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    End point title
    		 Core Study: Median Percent Change in Drop Seizure Frequency per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)
    End point description
    Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the subject’s head hitting a surface or that could have led to a fall or injury, depending on the subject’s position at the time of the attack or spell. The Full Analysis Set (FAS) was the group of randomized subjects who received at least one dose of the study drug and had at least one post-dose seizure measurement.
    End point type
    Primary
    End point timeframe
    Baseline up to 18 weeks
    End point values
    		 Core Study: Placebo Core Study: Perampanel
    Number of subjects analysed
    36
    34
    Units: percent change
    median (full range (min-max))
        Prerandomization (Baseline)
    77.65 (7.5 to 481.1)
    46.56 (6.2 to 645.0)
        Treatment Period
    -4.51 (-86.2 to 201.8)
    -23.07 (-96.4 to 371.4)
    Statistical analysis title
    		 Prerandomization, Treatment Period
    Statistical analysis description
    The median difference to placebo and the 95 percent (%) confidence interval (CI) were based on the Hodges-Lehmann method.
    Comparison groups
    Core Study: Placebo v Core Study: Perampanel
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.107 [1]
    Method
    		 ANCOVA
    Parameter type
    		 Median difference (net)
    Point estimate
    -19.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -49.2
         upper limit
    		 4.8
    Notes
    [1] - The p-value was based on a rank analysis of covariance (ANCOVA) with treatment, region, and age-group as factors, and prerandomization drop seizure frequency as a covariate.

    Secondary: Core Study: Median Percent Change in Total Seizure Frequency per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)

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    End point title
    		 Core Study: Median Percent Change in Total Seizure Frequency per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)
    End point description
    Total seizure was the number of seizures assessed and recorded by the subject's parent(s)/caregiver(s) in the subject seizure diary. Seizure diaries was used to collect seizure counts and types. The FAS was the group of randomized subjects who received at least one dose of the study drug and had at least one post-dose seizure measurement.
    End point type
    Secondary
    End point timeframe
    Baseline up to 18 weeks
    End point values
    		 Core Study: Placebo Core Study: Perampanel
    Number of subjects analysed
    36
    34
    Units: percent change
    median (full range (min-max))
        Prerandomization Phase (Baseline)
    110.76 (17.6 to 1754.3)
    142.55 (15.3 to 6858.0)
        Treatment Period
    -6.53 (-63.6 to 266.8)
    -18.23 (-96.9 to 103.5)
    No statistical analyses for this end point

    Secondary: Core Study: Percentage of Subjects with 50 Percent (%) Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures

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    End point title
    		 Core Study: Percentage of Subjects with 50 Percent (%) Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures
    End point description
    Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the subject’s head hitting a surface or that could have led to a fall or injury, depending on the subject’s position at the time of the attack or spell. A responder was a subject who experienced a 50% or greater reduction in drop seizure frequency per 28 days during Maintenance from prerandomization. The FAS was the group of randomized subjects who received at least one dose of the study drug and had at least one post-dose seizure measurement.
    End point type
    Secondary
    End point timeframe
    Baseline up to 18 weeks
    End point values
    		 Core Study: Placebo Core Study: Perampanel
    Number of subjects analysed
    36
    34
    Units: percentage of subjects
        number (not applicable)
    25.0
    44.1
    No statistical analyses for this end point

    Secondary: Core Study: Percentage of Subjects with 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Total Seizures

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    End point title
    		 Core Study: Percentage of Subjects with 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Total Seizures
    End point description
    Total seizure was the number of seizures assessed and recorded by the subject's parent(s)/caregiver(s) in the subject seizure diary. Seizure diaries was used to collect seizure counts and types. A responder was a subject who experienced a 50% or greater reduction in drop seizure frequency per 28 days during Maintenance from prerandomization. The FAS was the group of randomized subjects who received at least one dose of study drug and had at least one post-dose seizure measurement.
    End point type
    Secondary
    End point timeframe
    Baseline up to 18 weeks
    End point values
    		 Core Study: Placebo Core Study: Perampanel
    Number of subjects analysed
    36
    34
    Units: percentage of subjects
        number (not applicable)
    16.7
    32.4
    No statistical analyses for this end point

    Secondary: Core Study: Median Percent Change in Non-drop Seizure Frequency per 28 Days During Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline)

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    End point title
    		 Core Study: Median Percent Change in Non-drop Seizure Frequency per 28 Days During Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline)
    End point description
    Non-drop seizures were defined as non-drop attacks or spells. Drop attacks and spells involved the entire body, trunk, or head and lead to a fall, injury, slumping in a chair, or the subject's head hitting a surface, or could lead to a fall or injury, depending on the subject's position at the time of the attack or spell. The FAS was the group of randomized subjects who received at least one dose of study drug and had at least one post-dose seizure measurement. Here number of subjects analysed were subjects who were evaluable for the end point.
    End point type
    Secondary
    End point timeframe
    Baseline up to 18 weeks
    End point values
    		 Core Study: Placebo Core Study: Perampanel
    Number of subjects analysed
    30
    27
    Units: percent change
    median (full range (min-max))
        Prerandomization (Baseline)
    53.37 (1.1 to 1746.8)
    88.10 (1.0 to 6531.0)
        Treatment Phase
    -13.21 (-100.0 to 2288.1)
    -12.33 (-98.7 to 63.2)
    No statistical analyses for this end point

    Secondary: Core Study: Percentage of Subjects with 75% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures

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    End point title
    		 Core Study: Percentage of Subjects with 75% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures
    End point description
    Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the subject’s head hitting a surface or that could have led to a fall or injury, depending on the subject’s position at the time of the attack or spell. Non-drop seizures were defined as non-drop attacks or spells. Total seizure was the number of seizures assessed and recorded by the subject's parent(s)/caregiver(s) in the subject seizure diary. Seizure diaries was used to collect seizure counts and types. A responder was a subject who experienced a 75% or greater reduction in drop seizure/non-drop seizure/ frequency per 28 days during Maintenance from prerandomization. Here number analysed (n) were subjects who were evaluable for the end point at given categories. The FAS was the group of randomized subjects who received at least one dose of the study drug and had at least one post-dose seizure measurement.
    End point type
    Secondary
    End point timeframe
    Baseline up to 18 weeks
    End point values
    		 Core Study: Placebo Core Study: Perampanel
    Number of subjects analysed
    36
    34
    Units: percentage of subjects
    number (not applicable)
        Drop Seizures (n = 36, 34)
    13.9
    26.5
        Non-drop Seizures (n = 30, 27)
    10.0
    18.5
        Total Seizures (n = 36, 34)
    0
    11.8
    No statistical analyses for this end point

    Secondary: Core Study: Percentage of Subjects with 100% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures

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    End point title
    		 Core Study: Percentage of Subjects with 100% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures
    End point description
    Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the subject’s head hitting a surface or that could have led to a fall or injury, depending on the subject’s position at the time of the attack or spell. Non-drop seizures were defined as non-drop attacks or spells. Total seizure was the number of seizures assessed and recorded by the subject's parent(s)/caregiver(s) in the subject seizure diary. Seizure diaries was used to collect seizure counts and types. A responder was a subject who experienced a 100% or greater reduction in drop seizure/non-drop seizure/ frequency per 28 days during Maintenance from prerandomization. Here number analysed (n) were subjects who were evaluable for the end point at given categories. The FAS was the group of randomized subjects who received at least one dose of the study drug and had at least one post-dose seizure measurement.
    End point type
    Secondary
    End point timeframe
    Baseline up to 18 weeks
    End point values
    		 Core Study: Placebo Core Study: Perampanel
    Number of subjects analysed
    36
    34
    Units: percentage of subjects
    number (not applicable)
        Drop Seizure (n = 36, 34)
    0
    2.9
        Non-drop Seizure (n = 31, 28)
    6.5
    3.6
        Total Seizures (n = 36, 34)
    0
    2.9
    No statistical analyses for this end point

    Secondary: Core Study: Percentage of Subjects with 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Non-drop Seizures

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    End point title
    		 Core Study: Percentage of Subjects with 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Non-drop Seizures
    End point description
    Non-drop seizures were defined as non-drop attacks or spells. Drop attacks and spells involved the entire body, trunk, or head and lead to a fall, injury, slumping in a chair, or the subject's head hitting a surface, or could lead to a fall or injury, depending on the subject's position at the time of the attack or spell. A responder was a subject who experienced a 50% or greater reduction in non-drop seizure frequency per 28 days during Maintenance from prerandomization. Here number of subjects analysed were subjects who were evaluable for the end point. The FAS was the group of randomized subjects who received at least one dose of the study drug and had at least one post-dose seizure measurement.
    End point type
    Secondary
    End point timeframe
    Baseline up to 18 weeks
    End point values
    		 Core Study: Placebo Core Study: Perampanel
    Number of subjects analysed
    30
    27
    Units: percentage of subjects
        number (not applicable)
    16.7
    44.4
    No statistical analyses for this end point

    Secondary: Core Study: Percentage of Subjects With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase

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    End point title
    		 Core Study: Percentage of Subjects With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase
    End point description
    Assessment of disease severity utilized the CGIC scale at end of treatment to evaluate subjects change in disease status from baseline. The CGIC is a 7-point likert scale that measures a physician's global impression of a subjects clinical condition. Scale ranged from 1 to 7 with lower score indicated improvement (1=very much improved, 2=much improved, 3=minimally improved), higher score indicated worsening (5=minimally worse, 6= much worse, 7=very much worse), and a score of 4 indicated no change. Here number of subjects analysed were subjects who were evaluable for the end point. The FAS was the group of randomized subjects who received at least one dose of study drug and had at least one post-dose seizure measurement.
    End point type
    Secondary
    End point timeframe
    Baseline up to 18 weeks
    End point values
    		 Core Study: Placebo Core Study: Perampanel
    Number of subjects analysed
    35
    32
    Units: percentage of subjects
    number (not applicable)
        Very much improved
    0
    9.4
        Much improved
    8.6
    15.6
        Minimally improved
    25.7
    18.8
        No change
    57.1
    34.4
        Minimally worse
    5.7
    12.5
        Much worse
    2.9
    9.4
        Very much worse
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects with any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Number of Subjects with any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    End point description
    TEAE was defined as an adverse event with an onset date, or a worsening in severity from baseline (pre-treatment), on or after the first dose of study drug up to 28 days following study drug discontinuation. AE was defined as any untoward medical occurrence or clinical investigation in a subject administered an investigational product. AE does not necessarily have a causal relationship with a medicinal product. SAE was defined as any AE if resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. Subject Analysis Set (SAS) was group of subjects who received at least one dose of study drug and had at least one post-dose safety assessment. As per the planned safety analysis, safety data for Extension A and B were reported in a single arm of Extension Phase.
    End point type
    Secondary
    End point timeframe
    From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks)
    End point values
    		 Core Study: Placebo Core Study: Perampanel Extension Phase: Perampanel
    Number of subjects analysed
    36
    34
    58
    Units: subjects
        TEAEs
    26
    29
    50
        SAEs
    1
    6
    11
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-emergent Markedly Abnormal Laboratory Values

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    End point title
    		 Number of Subjects With Treatment-emergent Markedly Abnormal Laboratory Values
    End point description
    Treatment-emergent markedly abnormal value for laboratory values was based Common Terminology Criteria for Adverse events (CTCAE) Version 4.0, and determined as if the post baseline CTCAE Version 4.0 grade increases from baseline and the post baseline grade was >=2 (>=3 for phosphate). Laboratory tests included: Hematology count with differential, Chemistry (Electrolytes, Liver function tests, Renal function parameters, Other: albumin, cholesterol, glucose. SAS was group of subjects who received at least one dose of study drug and had at least one post-dose safety assessment.
    End point type
    Secondary
    End point timeframe
    From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks)
    End point values
    		 Core Study: Placebo Core Study: Perampanel Extension Phase: Perampanel
    Number of subjects analysed
    36
    34
    58
    Units: subjects
        Markedly Abnormal Low: Platelets
    1
    0
    0
        Markedly Abnormal Low: Neutrophils
    0
    1
    7
        Markedly Abnormal High: Gamma Glutamyl Transferase
    1
    1
    2
        Markedly Abnormal Low: Bicarbonate
    0
    1
    1
        Markedly Abnormal High: Sodium
    0
    1
    1
        Markedly Abnormal Low: Albumin
    0
    1
    0
        Markedly Abnormal High: Cholesterol
    0
    1
    1
        Markedly Abnormal High: Triglycerides
    2
    1
    4
        Markedly Abnormal Low: Haemoglobin
    0
    0
    1
        Markedly Abnormal Low: Lymphocytes
    0
    0
    2
        Markedly Abnormal Low: Leukocytes
    0
    0
    1
        Markedly Abnormal High: Alanine Aminotransferase
    0
    0
    1
        Markedly Abnormal Low: Glucose
    0
    0
    1
        Markedly Abnormal High: Alkaline Phosphatase
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Vital Signs

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    End point title
    		 Number of Subjects With Clinically Significant Vital Signs
    End point description
    Clinically significant means that a value must have met both the criterion value and satisfied the magnitude of change relative to baseline. Vital sign parameters included systolic blood pressure (BP), diastolic BP, pulse rate. SAS was group of subjects who received at least one dose of the study drug and had at least one post-dose safety assessment.
    End point type
    Secondary
    End point timeframe
    From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks)
    End point values
    		 Core Study: Placebo Core Study: Perampanel Extension Phase: Perampanel
    Number of subjects analysed
    36
    34
    58
    Units: subjects
        Systolic Blood Pressure: Low
    4
    2
    7
        Systolic Blood Pressure: High
    0
    0
    0
        Diastolic Blood Pressure: Low
    5
    1
    13
        Diastolic Blood Pressure: High
    0
    0
    0
        Pulse Rate: Low
    1
    0
    2
        Pulse Rate: High
    4
    5
    11
    No statistical analyses for this end point

    Secondary: Core Study: Model Predicted Average Perampanel Concentrations at Steady State (Cav,ss) During the Maintenance Period of Core Study

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    End point title
    		 Core Study: Model Predicted Average Perampanel Concentrations at Steady State (Cav,ss) During the Maintenance Period of Core Study
    End point description
    Due to the early termination of the study resulting in reduced sample size and the variability in treatment response, population PK analysis and population PK/PD modeling planned for this study were not conducted and hence data was not collected and analyzed for this end point.
    End point type
    Secondary
    End point timeframe
    Up to Week 18
    End point values
    		 Core Study: Placebo Core Study: Perampanel
    Number of subjects analysed
    0 [2]
    0 [3]
    Units: nanogram*hour per milliliter (ng*h/mL)
        arithmetic mean (standard deviation)
    ( )
    ( )
    Notes
    [2] - Pharmacokinetic analysis for this study was not conducted due to the early termination of the study.
    [3] - Pharmacokinetic analysis for this study was not conducted due to the early termination of the study.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From date of first administration of study drug up to 28 days after last dose of study drug (up to 192 weeks)
    Adverse event reporting additional description
    Subjects received varying doses in Extension Phase depending on tolerance but as target dose was defined as 12 mg/day for all subjects, AEs were summarized as a single arm. As per the planned safety analysis of Extension Phase, safety data for Extension A and Extension B was reported together in a single arm of Extension Phase.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Core Study: Perampanel
    Reporting group description
    		 Subjects received starting dose of perampanel, one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg parampanel), once daily at bedtime then up-titrated weekly in 2 mg increments to a target dose of 8 mg/day during titration period. During the maintenance period, subjects continued to receive the perampanel dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in the Core Study was 18 weeks.

    Reporting group title
    Core Study: Placebo
    Reporting group description
    		 Subjects received placebo matched to perampanel oral tablets or placebo matched to perampanel oral suspension (formulation was selected based on the subject’s condition and at the discretion of the investigator), once daily at bedtime during the titration period. During the maintenance period, subjects continued to receive the placebo matched to perampanel tablets or placebo matched to perampanel oral suspension at dose level that was administered at the end of the titration period. The total duration of the titration period (6 weeks) and maintenance period (12 weeks) in Core Study was 18 weeks.

    Reporting group title
    Extension Phase: Perampanel
    Reporting group description
    		 Subjects who completed Core Study entered Extension A. Subjects who received perampanel in Core Study, continued at dose received during Core maintenance period, and subjects who received placebo in Core Study started perampanel dose as one 2 mg oral tablet or 4 mL oral suspension (containing 2 mg perampanel) once daily at bedtime, then up-titrated weekly in 2 mg increments up to dose of 8 mg/day for 6 weeks conversion period. After conversion period, subjects could be titrated up to 12 mg/day in 2-week intervals during maintenance period (46 weeks) as per investigator’s discretion. Total duration of conversion and maintenance period in Extension Phase A was 52 weeks. Subjects who completed Extension A had option to enter into Extension B in countries where extended access program (EAP) could not be implemented, and received perampanel at optimal dose(dose at end of Extension A) until perampanel was available commercially or unless study termination(up to 188 weeks).

    Serious adverse events
    		 Core Study: Perampanel Core Study: Placebo Extension Phase: Perampanel
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 34 (17.65%)
    1 / 36 (2.78%)
    11 / 58 (18.97%)
         number of deaths (all causes)
    0
    0
    2
         number of deaths resulting from adverse events
    0
    0
    2
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 36 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 36 (0.00%)
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Quadriplegia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure cluster
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         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
    Microcytic anaemia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytogenetic abnormality
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    General disorders and administration site conditions
    Sudden unexplained death in epilepsy
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 36 (2.78%)
    0 / 58 (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
    Vomiting
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumatosis intestinalis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         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 aspiration
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 36 (2.78%)
    0 / 58 (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
    Respiratory distress
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 36 (0.00%)
    0 / 58 (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
    Cough
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 36 (2.78%)
    3 / 58 (5.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection viral
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         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
    Decreased appetite
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 36 (0.00%)
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 36 (0.00%)
    0 / 58 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         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
    		 Core Study: Perampanel Core Study: Placebo Extension Phase: Perampanel
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 34 (85.29%)
    26 / 36 (72.22%)
    50 / 58 (86.21%)
    Investigations
    Weight increased
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 36 (0.00%)
    2 / 58 (3.45%)
         occurrences all number
    2
    0
    2
    Injury, poisoning and procedural complications
    Skin laceration
         subjects affected / exposed
    2 / 34 (5.88%)
    1 / 36 (2.78%)
    3 / 58 (5.17%)
         occurrences all number
    2
    3
    4
    Contusion
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    3 / 58 (5.17%)
         occurrences all number
    0
    0
    3
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    3 / 34 (8.82%)
    0 / 36 (0.00%)
    5 / 58 (8.62%)
         occurrences all number
    3
    0
    5
    Drooling
         subjects affected / exposed
    3 / 34 (8.82%)
    1 / 36 (2.78%)
    5 / 58 (8.62%)
         occurrences all number
    4
    1
    5
    Lethargy
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 36 (0.00%)
    2 / 58 (3.45%)
         occurrences all number
    3
    0
    3
    Sedation
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 36 (0.00%)
    2 / 58 (3.45%)
         occurrences all number
    2
    0
    2
    Somnolence
         subjects affected / exposed
    8 / 34 (23.53%)
    2 / 36 (5.56%)
    11 / 58 (18.97%)
         occurrences all number
    8
    2
    12
    Ataxia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    3 / 58 (5.17%)
         occurrences all number
    0
    0
    3
    Dizziness
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    3 / 58 (5.17%)
         occurrences all number
    0
    0
    3
    Seizure
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    3 / 58 (5.17%)
         occurrences all number
    0
    0
    4
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 34 (8.82%)
    1 / 36 (2.78%)
    4 / 58 (6.90%)
         occurrences all number
    3
    1
    4
    Gait disturbance
         subjects affected / exposed
    3 / 34 (8.82%)
    0 / 36 (0.00%)
    4 / 58 (6.90%)
         occurrences all number
    3
    0
    6
    Peripheral swelling
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 36 (0.00%)
    2 / 58 (3.45%)
         occurrences all number
    2
    0
    2
    Pyrexia
         subjects affected / exposed
    1 / 34 (2.94%)
    5 / 36 (13.89%)
    8 / 58 (13.79%)
         occurrences all number
    1
    5
    9
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    3 / 34 (8.82%)
    1 / 36 (2.78%)
    3 / 58 (5.17%)
         occurrences all number
    3
    1
    3
    Nausea
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 36 (0.00%)
    3 / 58 (5.17%)
         occurrences all number
    2
    0
    4
    Vomiting
         subjects affected / exposed
    1 / 34 (2.94%)
    5 / 36 (13.89%)
    3 / 58 (5.17%)
         occurrences all number
    1
    5
    3
    Constipation
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 36 (0.00%)
    6 / 58 (10.34%)
         occurrences all number
    2
    0
    6
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 34 (5.88%)
    2 / 36 (5.56%)
    3 / 58 (5.17%)
         occurrences all number
    2
    3
    3
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    3 / 34 (8.82%)
    0 / 36 (0.00%)
    4 / 58 (6.90%)
         occurrences all number
    3
    0
    4
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 34 (2.94%)
    2 / 36 (5.56%)
    3 / 58 (5.17%)
         occurrences all number
    1
    2
    3
    Irritability
         subjects affected / exposed
    5 / 34 (14.71%)
    1 / 36 (2.78%)
    7 / 58 (12.07%)
         occurrences all number
    5
    1
    8
    Aggression
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    4 / 58 (6.90%)
         occurrences all number
    0
    0
    4
    Insomnia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 36 (0.00%)
    3 / 58 (5.17%)
         occurrences all number
    0
    0
    3
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 36 (8.33%)
    3 / 58 (5.17%)
         occurrences all number
    0
    3
    3
    Hordeolum
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 36 (0.00%)
    2 / 58 (3.45%)
         occurrences all number
    2
    0
    2
    Influenza
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 36 (0.00%)
    2 / 58 (3.45%)
         occurrences all number
    2
    0
    3
    Nasopharyngitis
         subjects affected / exposed
    2 / 34 (5.88%)
    2 / 36 (5.56%)
    7 / 58 (12.07%)
         occurrences all number
    4
    2
    15
    Pneumonia
         subjects affected / exposed
    2 / 34 (5.88%)
    1 / 36 (2.78%)
    2 / 58 (3.45%)
         occurrences all number
    2
    1
    2
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 34 (11.76%)
    1 / 36 (2.78%)
    7 / 58 (12.07%)
         occurrences all number
    7
    1
    11
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 34 (8.82%)
    0 / 36 (0.00%)
    6 / 58 (10.34%)
         occurrences all number
    3
    0
    6

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Dec 2016
    Protocol amendment 01: Revised exclusion criterion #17 to remove double-barrier contraception from set of acceptable methods, and to add recently updated safety language, added criteria for Hy’s Law and video electroencephalogram (EEG) to assessments, added Columbia Suicide Severity Rating Scale (C-SSRS) and language pertaining to suicidal behavior, and revised numbering of study weeks during extension phase and corrected the numbering of the study day at the end of Week 74.
    04 Jan 2017
    Protocol amendment 02: Added suicidal ideation to the list of exclusion criteria. Added instructions for laboratory abnormalities that might meet criteria for Hy’s Law (elevated aspartate aminotransferase [AST] or alanine aminotransferase [ALT] greater than or equal to 3*upper limit of normal [ULN] and elevated total bilirubin greater than or equal to 2*ULN with an alkaline phosphatase laboratory value that is less than 2*ULN) to be reported as serious adverse events. Added language allowing for discontinuation if the C-SSRS and/or clinical impression indicates a high risk of suicidal behavior. Corrected numbering of study weeks during Conversion Period of Extension Phase.
    24 Feb 2017
    Protocol amendment 03: Added that subjects with laboratory results that include elevated AST or ALT greater than or equal to 3*ULN and elevated total bilirubin greater than or equal to 2*ULN with an ALP laboratory value that is less than 2*ULN, that is, that meet criteria for Hy’s law will be withdrawn from the study. Added that subjects who appear to have a high risk of suicidal behavior according to results of the Columbia Suicide Severity Rating Scale (C-SSRS) and/or clinical impression will be withdrawn from the study.
    19 Oct 2018
    Protocol amendment 04: Added an additional extension phase (Extension B) for subjects in Japan or subjects in countries where an extended access program (EAP) cannot be implemented or has not yet been implemented, clarified inclusion criterion that subjects must have an average of at least 2 drop seizures per week during the Baseline Period, and added exclusion criterion that subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption will be excluded.
    19 Nov 2018
    Protocol amendment 05: Adjust the timing of Visit 8 from Week 20 to Week 21, and Visit 9 from Week 22 to Week 23. Update Study Day numbering for these two visits accordingly.

    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.
    Study was terminated early by sponsor due to recruitment challenge, further impacted by COVID19, resulting in reduced sample size and variability in treatment response.Planned population PK analysis were not conducted and data not collected/analysed.
    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.

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