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A Efficacy and Safety Study of Adjunctive Perampanel in Primary Generalized Tonic Clonic Seizures

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01393743
Recruitment Status : Completed
First Posted : July 13, 2011
Results First Posted : January 11, 2016
Last Update Posted : August 28, 2017
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Seizure Disorder Generalized Tonic Clonic
Interventions Drug: Perampanel
Drug: Placebo comparator
Enrollment 163
Recruitment Details  
Pre-assignment 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 prior to receiving treatment.
Arm/Group Title Placebo (Core Study) Perampanel (Core Study) Perampanel (Extension Phase)
Hide Arm/Group Description Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food. 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. The Extension Phase consisted of two parts: Part A (6-week blinded Conversion Period plus a 32-week Maintenance Period) and Part B (maximum of 104-week Maintenance Period), which was followed by an additional 4-week Follow-up Period. Part A: 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. During the 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. Participants who could not tolerate a dose of 2 mg/day perampanel during the Extension Period were discontinued from the study. The maximum dose of perampanel allowed during the Extension Phase was 12 mg/day.
Period Title: Core Study
Started 82 [1] 81 [1] 0
Completed 72 68 0
Not Completed 10 13 0
Reason Not Completed
Adverse Event             5             9             0
Lost to Follow-up             1             1             0
Participant's Choice             2             3             0
Inadequate therapeutic effect             2             0             0
[1]
Treated
Period Title: Extension Phase
Started 0 0 138 [1]
Completed 0 0 78
Not Completed 0 0 60
Reason Not Completed
Adverse Event             0             0             12
Lost to Follow-up             0             0             2
Participant choice             0             0             16
Inadequate therapeutic effect             0             0             7
Withdrawal by Subject             0             0             8
Pregnancy             0             0             1
Other             0             0             14
[1]
Continuation into the Extension Phase was optional.
Arm/Group Title Placebo (Core Study) Perampanel (Core Study) Total
Hide Arm/Group Description Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food. 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. Total of all reporting groups
Overall Number of Baseline Participants 82 81 163
Hide Baseline Analysis Population Description
The Core Study Full Analysis Set (FAS) and Extension Phase FAS included participants who were randomized to study drug, received at least 1 dose of study drug in that phase, had baseline and any postbaseline seizure frequency data during the Randomization Phase, and at least 1 observation of valid seizure diary data during treatment duration.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 82 participants 81 participants 163 participants
26
(14 to 70)
26
(12 to 58)
26
(12 to 70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 82 participants 81 participants 163 participants
Female
46
  56.1%
46
  56.8%
92
  56.4%
Male
36
  43.9%
35
  43.2%
71
  43.6%
1.Primary Outcome
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)
Hide 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.
Time Frame Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set included participants who were randomized to study drug, received at least 1 dose of study drug, and had any postbaseline seizure frequency data during the Randomization Phase.
Arm/Group Title Placebo (Core Study) Perampanel (Core Study)
Hide Arm/Group Description:
Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.
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.
Overall Number of Participants Analyzed 81 81
Median (Full Range)
Unit of Measure: Percent change
-38.38
(-100 to 1546.3)
-76.47
(-100 to 184.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Core Study), Perampanel (Core Study)
Comments The median difference to placebo and the 95% confidence interval are based on the Hodges-Lehmann method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments 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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -30.81
Confidence Interval (2-Sided) 95%
-45.49 to -15.244
Estimation Comments [Not Specified]
2.Primary Outcome
Title 50% Responder Rate for Primary Generalized Tonic Clonic Seizure During Maintenance - LOCF - (for Core Study)
Hide 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.
Time Frame Baseline (4 or 8 weeks) and Maintenance (13 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all randomized participants who received as least 1 dose of study drug and had any postbaseline seizure frequency data. Last observation carried forward (LOCF).
Arm/Group Title Placebo (Core Study) Perampanel (Core Study)
Hide Arm/Group Description:
Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.
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.
Overall Number of Participants Analyzed 81 81
Measure Type: Number
Unit of Measure: Percentage of participants
39.5 64.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Core Study), Perampanel (Core Study)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments The P value is based on non-missing values and is from a Cochran-Mantel-Haenszel test stratified by pooled country.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
3.Primary Outcome
Title 50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase)
Hide 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.
Time Frame Week 1 of perampanel treatment to date of last dose of perampanel in the Extension Phase
Hide Outcome Measure Data
Hide Analysis Population Description
The Extension Phase FAS included 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.
Arm/Group Title Perampanel Extension Phase
Hide Arm/Group Description:
The Extension Phase consisted of two parts: Part A (6-week blinded Conversion Period plus a 32-week Maintenance Period) and Part B (maximum of 104-week Maintenance Period), which was followed by an additional 4-week Follow-up 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, up to 12 mg/day perampanel maximum. 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. Participants who could not tolerate a dose of 2 mg/day perampanel during the Extension Period were discontinued from the study. The maximum dose of perampanel allowed during the Extension Phase was 12 mg/day.
Overall Number of Participants Analyzed 138
Measure Type: Number
Unit of Measure: Percentage of participants
Core Study Maintenanace Period 55.1
Extension Conversion Period 74.6
Extension Maintenance Weeks 1 to 13 75.9
Extension Maintenance Weeks 14 to 26 78.4
Extension Maintenance Weeks 27 to 39 78.1
Extension Maintenance Weeks 40 to 52 79.8
Extension Maintenance Weeks 53 to 65 81.8
Extension Maintenance Weeks 66 to 78 76.5
Extension Maintenance Weeks 79 to 91 80.3
Extension Maintenance Weeks 92 to 104 91.4
4.Secondary Outcome
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)
Hide 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.
Time Frame Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Placebo (Core Study) Perampanel (Core Study)
Hide Arm/Group Description:
Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.
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.
Overall Number of Participants Analyzed 81 81
Median (Full Range)
Unit of Measure: Percent Change
-22.87
(-100 to 125.7)
-43.4
(-100 to 1366.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Core Study), Perampanel (Core Study)
Comments The median difference to placebo and the 95% confidence interval are based on the Hodges-Lehmann method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments 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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -23.45
Confidence Interval (2-Sided) 95%
-40.668 to -8.518
Estimation Comments [Not Specified]
5.Secondary Outcome
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)
Hide 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.
Time Frame Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Placebo (Core Study) Perampanel (Core Study)
Hide Arm/Group Description:
Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.
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.
Overall Number of Participants Analyzed 81 81
Median (Full Range)
Unit of Measure: Percent Change
Absence Number Analyzed 33 participants 27 participants
-7.58
(-100 to 592.4)
-41.18
(-100 to 8088.2)
Myoclonic Number Analyzed 23 participants 24 participants
-52.54
(-100 to 321.2)
-24.47
(-100 to 482.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Core Study), Perampanel (Core Study)
Comments Median Difference to Placebo for Absence Seizures
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3478
Comments 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.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -12.25
Confidence Interval (2-Sided) 95%
-53.054 to 26.989
Estimation Comments The median difference to placebo and the 95% confidence interval are based on the Hodges-Lehmann method.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Core Study), Perampanel (Core Study)
Comments Median Difference to Placebo for Myoclonic Seizure
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 24.87
Confidence Interval (2-Sided) 95%
-15.338 to 59.938
Estimation Comments [Not Specified]
6.Secondary Outcome
Title 50% Responder Rate for All Seizures During Maintenance-LOCF - (for Core Study)
Hide 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.
Time Frame Baseline (4 or 8 weeks) and Maintenance (13 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Placebo (Core Study) Perampanel (Core Study)
Hide Arm/Group Description:
Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.
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.
Overall Number of Participants Analyzed 81 81
Measure Type: Number
Unit of Measure: Percentage of participants
34.6 45.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Core Study), Perampanel (Core Study)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1826
Comments The P value is based on non-missing values and is from a Cochran-Mantel-Haenszel test stratified by pooled country.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
7.Secondary Outcome
Title 50% Responder Rate for Primary Generalized Seizure Subtype During Maintenance Period - LOCF - (for Core Study)
Hide 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 - (LOCF) from prerandomization. The data was presented as the percentage of participants.
Time Frame Baseline (4 or 8 weeks) and Maintenance (13 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Only a subset of participants in the Full Analysis Set who experienced these seizure types during the Prerandomization Phase of the study were included in this analysis.
Arm/Group Title Placebo (Core Study) Perampanel (Core Study)
Hide Arm/Group Description:
Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.
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.
Overall Number of Participants Analyzed 81 81
Measure Type: Number
Unit of Measure: Percentage of participants
Absence Number Analyzed 33 participants 27 participants
39.4 48.1
Myoclonic Number Analyzed 23 participants 24 participants
60.9 41.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Core Study), Perampanel (Core Study)
Comments P Value Compared to Placebo for Absence Seizures
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4653
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Core Study), Perampanel (Core Study)
Comments P Value Compared to Placebo for Myoclonic Seizures
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3694
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
8.Secondary Outcome
Title Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase)
Hide 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.
Time Frame Date of first dose of study drug to date of last dose of study drug in the Extension Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were eligible to participate in the Extension Phase, received at least 1 dose of perampanel in this phase, and had baseline seizure frequency data and at least 1 observation of valid seizure diary data during the perampanel treatment duration.
Arm/Group Title Perampanel (Extension Phase)
Hide Arm/Group Description:
The Extension Phase consisted of two parts: Part A (6-week blinded Conversion Period plus a 32-week Maintenance Period) and Part B (maximum of 104-week Maintenance Period), which was followed by an additional 4-week Follow-up Period. Part A: 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. During the 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. Participants who could not tolerate a dose of 2 mg/day perampanel during the Extension Period were discontinued from the study. The maximum dose of perampanel allowed during the Extension Phase was 12 mg/day.
Overall Number of Participants Analyzed 138
Median (Full Range)
Unit of Measure: Percent change in PGTC seizure frequency
Core Study Titration Period Number Analyzed 138 participants
-57.72
(-100.0 to 500.0)
Core Study Maintenance Period Number Analyzed 138 participants
-57.40
(-100.0 to 2011.6)
Extension Phase Conversion Period Number Analyzed 138 participants
-100.00
(-100.0 to 166.7)
Extension Phase Maintenance Period, Weeks 1 to 13 Number Analyzed 133 participants
-84.62
(-100.0 to 594.5)
Extension Phase Maintenance Period, Weeks 14 to 26 Number Analyzed 125 participants
-86.81
(-100.0 to 186.2)
Extension Phase Maintenance Period, Weeks 27 to 39 Number Analyzed 114 participants
-86.62
(-100.0 to 250.8)
Extension Phase Maintenance Period, Weeks 40 to 52 Number Analyzed 104 participants
-100.00
(-100.0 to 146.2)
Extension Phase Maintenance Period, Weeks 53 to 65 Number Analyzed 99 participants
-100.00
(-100.0 to 150.5)
Extension Phase Maintenance Period, Weeks 66 to 78 Number Analyzed 68 participants
-100.00
(-100.0 to 108.8)
Extension Phase Maintenance, Weeks 79 to 91 Number Analyzed 61 participants
-100.00
(-100.0 to 140.1)
Extension Phase Maintenance, Weeks 92 to 104 Number Analyzed 35 participants
-100.00
(-100.0 to 171.4)
9.Secondary Outcome
Title Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase)
Hide 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set, which comprised all participants who were eligible to participate in the Extension Phase, received at least 1 dose of perampanel in this phase, and had baseline seizure frequency data and at least 1 observation of valid seizure diary data during the perampanel treatment duration.
Arm/Group Title PGTC Seizures All Seizures
Hide Arm/Group 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.
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.
Overall Number of Participants Analyzed 138 138
Median (Full Range)
Unit of Measure: Percent change in seizure frequency
Weeks 1 to 13 Number Analyzed 138 participants 138 participants
-77.45
(-100.0 to 676.9)
-56.54
(-100.0 to 1130.8)
Weeks 14 to 26 Number Analyzed 133 participants 133 participants
-74.21
(-100.0 to 191.7)
-63.53
(-100.0 to 1253.8)
Weeks 27 to 39 Number Analyzed 125 participants 125 participants
-84.62
(-100.0 to 264.4)
-79.49
(-100.0 to 1100.0)
Weeks 40 to 52 Number Analyzed 118 participants 118 participants
-89.65
(-100.0 to 171.9)
-83.38
(-100.0 to 855.6)
Weeks 53 to 65 Number Analyzed 109 participants 109 participants
-92.45
(-100.0 to 49.6)
-83.33
(-100.0 to 54.8)
Weeks 66 to 78 Number Analyzed 90 participants 90 participants
-100.00
(-100.0 to 92.3)
-88.71
(-100.0 to 100.5)
Weeks 79 to 91 Number Analyzed 80 participants 80 participants
-100.00
(-100.0 to 700.0)
-90.28
(-100.0 to 700.0)
Weeks 92 to 104 Number Analyzed 52 participants 52 participants
-100.00
(-100.0 to 171.4)
-98.96
(-100.0 to 394.4)
Weeks 105 to 117 Number Analyzed 41 participants 41 participants
-100.00
(-100.0 to 118.2)
-96.42
(-100.0 to 118.2)
Weeks 118 to 130 Number Analyzed 27 participants 27 participants
-100.00
(-100.0 to -8.5)
-96.58
(-100.0 to 27.8)
Weeks 131 to 143 Number Analyzed 19 participants 19 participants
-100.00
(-100.0 to 20.1)
-91.70
(-100.0 to -52.7)
Weeks greater than or equal to 144 Number Analyzed 9 participants 9 participants
-100.00
(-100.0 to -71.5)
-82.09
(-100.0 to -31.3)
10.Secondary Outcome
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)
Hide 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.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included participants who were randomized to study drug, received at least 1 dose of study drug, and had at least 1 postbaseline safety assessment.
Arm/Group Title Placebo (Core Study) Perampanel (Core Study)
Hide Arm/Group Description:
Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.
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.
Overall Number of Participants Analyzed 82 81
Measure Type: Number
Unit of Measure: Participants
Treatment emergent adverse events 59 67
Treatment emergent serious adverse events 7 6
Time Frame 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 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.
 
Arm/Group Title Placebo (Core Study) Perampanel (Core Study) Perampanel (Extension Phase)
Hide Arm/Group Description Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food. 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. The Extension Phase consisted of two parts: Part A (6-week blinded Conversion Period plus a 32-week Maintenance Period) and Part B (maximum of 104-week Maintenance Period), which was followed by an additional 4-week Follow-up Period. Part A: 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. During the 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. Participants who could not tolerate a dose of 2 mg/day perampanel during the Extension Period were discontinued from the study. The maximum dose of perampanel allowed during the Extension Phase was 12 mg/day.
All-Cause Mortality
Placebo (Core Study) Perampanel (Core Study) Perampanel (Extension Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo (Core Study) Perampanel (Core Study) Perampanel (Extension Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/82 (8.54%)   6/81 (7.41%)   18/138 (13.04%) 
Blood and lymphatic system disorders       
Disseminated intravascular coagulation  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Eye disorders       
Retinal detachment  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Gastrointestinal disorders       
Constipation  1  0/82 (0.00%)  1/81 (1.23%)  1/138 (0.72%) 
Nausea  1  1/82 (1.22%)  0/81 (0.00%)  0/138 (0.00%) 
Pancreatitis acute  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
General disorders       
Drowning  1  0/82 (0.00%)  1/81 (1.23%)  0/138 (0.00%) 
Hepatobiliary disorders       
Cholecystitis Chronic  1  0/82 (0.00%)  1/81 (1.23%)  0/138 (0.00%) 
Infections and infestations       
Diverticulitis  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Pneumonia  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Septic shock  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Injury, poisoning and procedural complications       
Fall  1  1/82 (1.22%)  0/81 (0.00%)  0/138 (0.00%) 
Thermal Burn  1  1/82 (1.22%)  0/81 (0.00%)  0/138 (0.00%) 
Facial bones fracture  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Fibula fracture  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Tibia fracture  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Wound  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Metabolism and nutrition disorders       
Dehydration  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Musculoskeletal and connective tissue disorders       
Intervertebral disc protrusion  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Endometrial adenocarcinoma  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Nervous system disorders       
Convulsion  1  2/82 (2.44%)  1/81 (1.23%)  3/138 (2.17%) 
Grand Mal Convulsion  1  1/82 (1.22%)  0/81 (0.00%)  1/138 (0.72%) 
Status Epilepticus  1  1/82 (1.22%)  1/81 (1.23%)  0/138 (0.00%) 
Sedation  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous incomplete  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Psychiatric disorders       
Suicidal Ideation  1  0/82 (0.00%)  1/81 (1.23%)  1/138 (0.72%) 
Suicide Attempt  1  0/82 (0.00%)  1/81 (1.23%)  2/138 (1.45%) 
Aggression  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Depression  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Mental disorder  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Mental status changes  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Psychiatric symptom  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Psychogenic seizure  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Reproductive system and breast disorders       
Endometrial hyperplasia  1  0/82 (0.00%)  0/81 (0.00%)  1/138 (0.72%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA VERSION 16.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo (Core Study) Perampanel (Core Study) Perampanel (Extension Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   56/82 (68.29%)   67/81 (82.72%)   106/138 (76.81%) 
Ear and labyrinth disorders       
Vertigo  1  2/82 (2.44%)  7/81 (8.64%)  15/138 (10.87%) 
Gastrointestinal disorders       
Abdominal Pain  1  1/82 (1.22%)  4/81 (4.94%)  8/138 (5.80%) 
Nausea  1  3/82 (3.66%)  5/81 (6.17%)  11/138 (7.97%) 
Vomiting  1  2/82 (2.44%)  7/81 (8.64%)  9/138 (6.52%) 
General disorders       
Fatigue  1  5/82 (6.10%)  12/81 (14.81%)  14/138 (10.14%) 
Irritability  1  2/82 (2.44%)  9/81 (11.11%)  19/138 (13.77%) 
Infections and infestations       
Nasopharyngitis  1  7/82 (8.54%)  7/81 (8.64%)  20/138 (14.49%) 
Upper Respiratory Tract Infection  1  5/82 (6.10%)  4/81 (4.94%)  18/138 (13.04%) 
Injury, poisoning and procedural complications       
Contusion  1  3/82 (3.66%)  5/81 (6.17%)  12/138 (8.70%) 
Investigations       
Weight Increased  1  3/82 (3.66%)  6/81 (7.41%)  13/138 (9.42%) 
Nervous system disorders       
Dizziness  1  5/82 (6.10%)  26/81 (32.10%)  53/138 (38.41%) 
Headache  1  8/82 (9.76%)  10/81 (12.35%)  17/138 (12.32%) 
Somnolence  1  3/82 (3.66%)  9/81 (11.11%)  18/138 (13.04%) 
Psychiatric disorders       
Anxiety  1  3/82 (3.66%)  4/81 (4.94%)  7/138 (5.07%) 
Insomnia  1  4/82 (4.88%)  3/81 (3.70%)  12/138 (8.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA VERSION 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Eisai Medical Services
Organization: Eisai, Inc.
Phone: 1-888-422-4743
EMail: esi_medinfo@eisai.com
Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01393743    
Other Study ID Numbers: E2007-G000-332
First Submitted: July 12, 2011
First Posted: July 13, 2011
Results First Submitted: May 29, 2015
Results First Posted: January 11, 2016
Last Update Posted: August 28, 2017