A Efficacy and Safety Study of Adjunctive Perampanel in Primary Generalized Tonic Clonic Seizures - Full Text View

Purpose

This study is designed to evaluate the efficacy, safety, and pharmacokinetics (PK) of perampanel on Primary Generalized Tonic Clonic (PGTC) seizure frequency in adolescents and adults maintained on one to two stable antiepileptic drugs.

Condition	Intervention	Phase
Seizure Disorder Generalized Tonic Clonic	Drug: perampanel Drug: Placebo comparator	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Adjunctive Perampanel in Primary Generalized Tonic Clonic Seizures

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Seizures

Drug Information available for: Perampanel

U.S. FDA Resources

Further study details as provided by Eisai Inc.:

Primary Outcome Measures:

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 [ Time Frame: Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks) ] [ Designated as safety issue: No ]
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.
50% Responder Rate for Primary Generalized Tonic Clonic Seizure During Maintenance-LOCF (for Core Study) [ Time Frame: Baseline (4 or 8 weeks) and Maintenance (13 weeks) ] [ Designated as safety issue: No ]
A responder is 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 is presented as percentage of participants.

Secondary Outcome Measures:

Median Percent Change in All Seizure Frequency Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization)- for Core Study [ Time Frame: Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks) ] [ Designated as safety issue: No ]
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.
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 [ Time Frame: Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks) ] [ Designated as safety issue: No ]
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.
50% Responder Rate for All Seizure During Maintenance-LOCF (for Core Study) [ Time Frame: Baseline (4 or 8 weeks) and Maintenance (13 weeks) ] [ Designated as safety issue: No ]
All seizures includes PGTC, myoclonic, absence and all other seizures that occur during the study. A responder is a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance- LOCF from prerandomization. The data is presented as percentage of participants.
50% Responder Rate for Primary Generalized Seizure Subtype During Maintenance-LOCF (for Core Study) [ Time Frame: Baseline (4 or 8 weeks) and Maintenance (13 weeks) ] [ Designated as safety issue: No ]
Primary generalized seizure subtype includes absence and myoclonic seizures. A responder is 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 is presented as percentage of 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 [ 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. ] [ Designated as safety issue: Yes ]
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 (ie, 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.


Enrollment:	164
Study Start Date:	September 2011
Study Completion Date:	November 2015
Primary Completion Date:	May 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Perampanel 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/placebo.	Drug: perampanel
Placebo Comparator: Placebo Participants received 6 tablets of perampanel matched placebo, once a day.	Drug: Placebo comparator

Detailed Description:

This study is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, adjunctive-therapy study with an open-label Extension Phase. The Core Study consists of 2 phases: Prerandomization and Randomization. The Prerandomization Phase consisted of 2 periods: Screening (up to 4 weeks) and Baseline (4 or 8 weeks, depending on the accuracy of diary-documented seizures during Screening), during which participants will be assessed for eligibility to participate in the study. The Randomization Phase consisted of 3 periods: Titration (4 weeks), Maintenance (13 weeks), and Follow-up (4 weeks; only for those participants not entering into the Extension Phase). At the start of the Randomization Phase, eligible participants will be randomized to the perampanel or placebo treatment groups in a 1:1 ratio. The extension phase consists of 142 weeks.

Eligibility


Ages Eligible for Study:	12 Years and older (Child, Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion:

Clinical diagnosis of PGTC seizures (with or without other subtypes of primary generalized seizures) and experiencing greater than or equal to 3 PGTC seizures during the 8-week period prior to randomization
Have had a routine electroencephalogram (EEG) prior to or during the Baseline Period with electroencephalographic features consistent with primary generalized epilepsy; other concomitant anomaly should be explained by adequate past medical history
On a fixed dose of one to a maximum of three concomitant antiepileptic drugs (AEDs) for a minimum of 30 days prior to Baseline; only one inducer AED (i.e., carbamazepine, oxcarbazepine, or phenytoin) out of the maximum of two AEDs will be allowed
A vagal nerve stimulator (VNS) will be allowed, but it must have been implanted greater than or equal to 5 months prior to Baseline (stimulator parameters cannot be changed for 30 days prior to Baseline and for the duration of the study).
Have had a computed tomography (CT) or magnetic resonance imaging (MRI) within the last 10 years (for adults) and 5 years (for adolescents) that ruled out a progressive cause of epilepsy
A ketogenic diet will be allowed as long as the participant has been on this diet for 5 weeks prior to randomization

Exclusion:

A history of status epilepticus that required hospitalization within 12 months prior to Baseline
Seizure clusters where individual seizures cannot be counted
A history of psychogenic seizures
Concomitant diagnosis of Partial Onset Seizures (POS)
Progressive neurological disease
Clinical diagnosis of Lennox-Gastaut syndrome
If felbamate is used as a concomitant AED, participants must be on felbamate for at least 2 years, with a stable dose for 60 days prior to Baseline. They must not have a history of white blood cell (WBC) count below less than or equal to 2500/microL (2.50 1E+09/L), platelets less than 100,000/microL, liver function tests (LFTs) greater than 3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate.
Concomitant use of vigabatrin: Participants who took vigabatrin in the past must be discontinued for approximately 5 months prior to Baseline, and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in an automated visual perimetry test
Concomitant use of barbiturates (except for seizure control indication) within 30 days prior to Baseline
Use of intermittent rescue benzodiazepines (i.e., one to two doses over a 24-hour period considered one-time rescue) two or more times within the 30 days prior to Baseline

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01393743

Sponsors and Collaborators

Eisai Inc.

Investigators


Study Director:	Francesco Bibbiani	Eisai Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

French JA, Krauss GL, Wechsler RT, Wang XF, DiVentura B, Brandt C, Trinka E, O'Brien TJ, Laurenza A, Patten A, Bibbiani F. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized trial. Neurology. 2015 Sep 15;85(11):950-7.


Responsible Party:	Eisai Inc.
ClinicalTrials.gov Identifier:	NCT01393743 History of Changes
Other Study ID Numbers:	E2007-G000-332
Study First Received:	July 12, 2011
Results First Received:	May 29, 2015
Last Updated:	December 7, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eisai Inc.:


Central Nervous System

Additional relevant MeSH terms:


Seizures Epilepsy Brain Diseases Central Nervous System Diseases	Nervous System Diseases Neurologic Manifestations Signs and Symptoms

ClinicalTrials.gov processed this record on September 26, 2016