Trial Outcomes & Findings for A Efficacy and Safety Study of Adjunctive Perampanel in Primary Generalized Tonic Clonic Seizures (NCT NCT01393743)

Last Updated: 2017-08-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

163 participants

Primary outcome timeframe

Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)

Results posted on

2017-08-28

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Placebo (Core Study) Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) 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.	Perampanel (Extension Phase) 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.
Core Study STARTED	82	81	0
Core Study COMPLETED	72	68	0
Core Study NOT COMPLETED	10	13	0
Extension Phase STARTED	0	0	138
Extension Phase COMPLETED	0	0	78
Extension Phase NOT COMPLETED	0	0	60

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (Core Study) Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) 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.	Perampanel (Extension Phase) 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.
Extension Phase Other	0	0	14
Core Study Adverse Event	5	9	0
Core Study Lost to Follow-up	1	1	0
Core Study Participant's Choice	2	3	0
Core Study Inadequate therapeutic effect	2	0	0
Extension Phase Adverse Event	0	0	12
Extension Phase Lost to Follow-up	0	0	2
Extension Phase Participant choice	0	0	16
Extension Phase Inadequate therapeutic effect	0	0	7
Extension Phase Withdrawal by Subject	0	0	8
Extension Phase Pregnancy	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Core Study) n=82 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) n=81 Participants 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 n=163 Participants Total of all reporting groups
Age, Continuous	26 Years n=5 Participants	26 Years n=7 Participants	26 Years n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	46 Participants n=7 Participants	92 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	35 Participants n=7 Participants	71 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo (Core Study) n=81 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) n=81 Participants 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.
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)	-38.38 Percent change Interval -100.0 to 1546.3	-76.47 Percent change Interval -100.0 to 184.5

PRIMARY outcome

Timeframe: Baseline (4 or 8 weeks) and Maintenance (13 weeks)

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Placebo (Core Study) n=81 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) n=81 Participants 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.
50% Responder Rate for Primary Generalized Tonic Clonic Seizure During Maintenance - LOCF - (for Core Study)	39.5 Percentage of participants	64.2 Percentage of participants

PRIMARY outcome

Timeframe: Week 1 of perampanel treatment to date of last dose of perampanel in the Extension Phase

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Core Study) n=138 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) 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.
50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) Core Study Maintenanace Period	55.1 Percentage of participants	—
50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) Extension Conversion Period	74.6 Percentage of participants	—
50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) Extension Maintenance Weeks 1 to 13	75.9 Percentage of participants	—
50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) Extension Maintenance Weeks 14 to 26	78.4 Percentage of participants	—
50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) Extension Maintenance Weeks 27 to 39	78.1 Percentage of participants	—
50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) Extension Maintenance Weeks 40 to 52	79.8 Percentage of participants	—
50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) Extension Maintenance Weeks 53 to 65	81.8 Percentage of participants	—
50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) Extension Maintenance Weeks 66 to 78	76.5 Percentage of participants	—
50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) Extension Maintenance Weeks 79 to 91	80.3 Percentage of participants	—
50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) Extension Maintenance Weeks 92 to 104	91.4 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Placebo (Core Study) n=81 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) n=81 Participants 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.
Median Percent Change in All Seizure Frequency Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study)	-22.87 Percent Change Interval -100.0 to 125.7	-43.4 Percent Change Interval -100.0 to 1366.7

SECONDARY outcome

Timeframe: Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks)

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Placebo (Core Study) n=81 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) n=81 Participants 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.
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) Absence	-7.58 Percent Change Interval -100.0 to 592.4	-41.18 Percent Change Interval -100.0 to 8088.2
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) Myoclonic	-52.54 Percent Change Interval -100.0 to 321.2	-24.47 Percent Change Interval -100.0 to 482.4

SECONDARY outcome

Timeframe: Baseline (4 or 8 weeks) and Maintenance (13 weeks)

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Placebo (Core Study) n=81 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) n=81 Participants 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.
50% Responder Rate for All Seizures During Maintenance-LOCF - (for Core Study)	34.6 Percentage of participants	45.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (4 or 8 weeks) and Maintenance (13 weeks)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Core Study) n=81 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) n=81 Participants 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.
50% Responder Rate for Primary Generalized Seizure Subtype During Maintenance Period - LOCF - (for Core Study) Absence	39.4 Percentage of participants	48.1 Percentage of participants
50% Responder Rate for Primary Generalized Seizure Subtype During Maintenance Period - LOCF - (for Core Study) Myoclonic	60.9 Percentage of participants	41.7 Percentage of participants

SECONDARY outcome

Timeframe: Date of first dose of study drug to date of last dose of study drug in the Extension Phase

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Core Study) n=138 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) 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.
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Core Study Titration Period	-57.72 Percent change in PGTC seizure frequency Interval -100.0 to 500.0	—
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Core Study Maintenance Period	-57.40 Percent change in PGTC seizure frequency Interval -100.0 to 2011.6	—
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Extension Phase Conversion Period	-100.00 Percent change in PGTC seizure frequency Interval -100.0 to 166.7	—
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Extension Phase Maintenance Period, Weeks 1 to 13	-84.62 Percent change in PGTC seizure frequency Interval -100.0 to 594.5	—
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Extension Phase Maintenance Period, Weeks 14 to 26	-86.81 Percent change in PGTC seizure frequency Interval -100.0 to 186.2	—
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Extension Phase Maintenance Period, Weeks 27 to 39	-86.62 Percent change in PGTC seizure frequency Interval -100.0 to 250.8	—
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Extension Phase Maintenance Period, Weeks 40 to 52	-100.00 Percent change in PGTC seizure frequency Interval -100.0 to 146.2	—
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Extension Phase Maintenance Period, Weeks 53 to 65	-100.00 Percent change in PGTC seizure frequency Interval -100.0 to 150.5	—
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Extension Phase Maintenance Period, Weeks 66 to 78	-100.00 Percent change in PGTC seizure frequency Interval -100.0 to 108.8	—
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Extension Phase Maintenance, Weeks 79 to 91	-100.00 Percent change in PGTC seizure frequency Interval -100.0 to 140.1	—
Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) Extension Phase Maintenance, Weeks 92 to 104	-100.00 Percent change in PGTC seizure frequency Interval -100.0 to 171.4	—

SECONDARY outcome

Timeframe: Weeks: 1 to 13, 14 to 26, 27 to 39, 40 to 52, 53 to 65, 66 to 78, 79 to 91, 92 to 104, 105 to 117, 118 to 130, 131 to 143, greater than or equal to 144

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Core Study) n=138 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) n=138 Participants 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.
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 14 to 26	-74.21 Percent change in seizure frequency Interval -100.0 to 191.7	-63.53 Percent change in seizure frequency Interval -100.0 to 1253.8
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 105 to 117	-100.00 Percent change in seizure frequency Interval -100.0 to 118.2	-96.42 Percent change in seizure frequency Interval -100.0 to 118.2
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks greater than or equal to 144	-100.00 Percent change in seizure frequency Interval -100.0 to -71.5	-82.09 Percent change in seizure frequency Interval -100.0 to -31.3
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 1 to 13	-77.45 Percent change in seizure frequency Interval -100.0 to 676.9	-56.54 Percent change in seizure frequency Interval -100.0 to 1130.8
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 27 to 39	-84.62 Percent change in seizure frequency Interval -100.0 to 264.4	-79.49 Percent change in seizure frequency Interval -100.0 to 1100.0
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 40 to 52	-89.65 Percent change in seizure frequency Interval -100.0 to 171.9	-83.38 Percent change in seizure frequency Interval -100.0 to 855.6
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 53 to 65	-92.45 Percent change in seizure frequency Interval -100.0 to 49.6	-83.33 Percent change in seizure frequency Interval -100.0 to 54.8
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 66 to 78	-100.00 Percent change in seizure frequency Interval -100.0 to 92.3	-88.71 Percent change in seizure frequency Interval -100.0 to 100.5
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 79 to 91	-100.00 Percent change in seizure frequency Interval -100.0 to 700.0	-90.28 Percent change in seizure frequency Interval -100.0 to 700.0
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 92 to 104	-100.00 Percent change in seizure frequency Interval -100.0 to 171.4	-98.96 Percent change in seizure frequency Interval -100.0 to 394.4
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 118 to 130	-100.00 Percent change in seizure frequency Interval -100.0 to -8.5	-96.58 Percent change in seizure frequency Interval -100.0 to 27.8
Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) Weeks 131 to 143	-100.00 Percent change in seizure frequency Interval -100.0 to 20.1	-91.70 Percent change in seizure frequency Interval -100.0 to -52.7

SECONDARY outcome

Timeframe: For each participant, from the first treatment dose till 30 days after the last dose or up to 21 weeks for core study and 142 weeks for extension phase.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo (Core Study) n=82 Participants Participants received 6 tablets of perampanel matched placebo, once a day, before bedtime and with food.	Perampanel (Core Study) n=81 Participants Participants received 6 tablets (initially ,1 tablet of 2 mg perampanel plus 5 tablets of perampanel matched placebo) and up-titrated weekly in 2 mg increments to a target dose range of 8 mg per day maintaining the blind with administration of 6 tablets per day of either perampanel/perampanel matched placebo.
Number of 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) Treatment emergent adverse events	59 Participants	67 Participants
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) Treatment emergent serious adverse events	7 Participants	6 Participants

Adverse Events

Placebo (Core Study)

Serious events: 7 serious events

Other events: 56 other events

Deaths: 0 deaths

Perampanel (Core Study)

Serious events: 6 serious events

Other events: 67 other events

Deaths: 0 deaths

Perampanel (Extension Phase)

Serious events: 18 serious events

Other events: 106 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Eisai Medical Services

Eisai, Inc.

Phone: 1-888-422-4743

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER