Inadequately controlled partial onset seizures
Conditions
Interventions
Product Name: perampanel
Product Code: E2007, MARS
Pharmaceutical Form: Tablet
INN or Proposed INN: Perampanel
Current Sponsor code: E2007
Other descriptive name: MARS
Concentration unit: mg milligram
Sponsors
Eisai Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Core Study: - Considered reliable and willing to be available for the study duration and is able to record seizures and report adverse events (AEs) themselves or have a legal guardian or a caregiver who can record seizures and report AEs for them - Understand the requirements of the CDR System tests and able to perform the tests appropriately at Visit 1 - Male or female, 12 to less than 18 years of age at the time of consent/assent - Have a diagnosis of epilepsy with partial-onset seizures with or without secondarily generalized seizures according to the International League Against Epilepsy’s (ILAE) Classification of Epileptic Seizures (1981). Diagnosis should have been established at least 6 months prior to Visit 1, by clinical history and an EEG that is consistent with localization-related epilepsy; normal interictal EEGs will be allowed provided that the subject meets the other diagnosis criterion (ie, clinical history) - Have had a brain imaging (eg, magnetic resonance imaging [MRI] scan or computed tomography[CT]) within the 5 years prior to Visit 1 that ruled out a progressive cause of epilepsy - Must have had at least 1 partial-onset seizure during the 4 weeks prior to Visit 1 despite a stable regimen of 1 to 3 concomitant AEDs - Are currently being treated with stable doses of 1-3 AEDs. Only 1 inducer AED (either carbamazepine or phenytoin) out of the maximum of 3 AEDs is allowed - Are on a stable dose of the same concomitant AED(s) for at least 4 weeks prior to Visit 1; in the case where a new AED regimen has been initiated for a subject, the dose must be stable for at least 8 weeks prior to Visit 1 - Female subjects of childbearing potential must have a negative serum human chorionic gonadotropin (ß-hCG) at Visit 1 and a negative urine pregnancy test prior to randomization at Visit 2. Female subjects of childbearing potential must agree for the duration of the study and for a period of at least 60 days following administration of the last dose of study medication to commit to the consistent and correct use of a medically acceptable method of birth control (eg, a double-barrier method [condom + spermicide, condom + diaphragm with spermicide]). Abstinence will be considered an acceptable method of contraception on a case by case basis upon prior approval by the Medical Monitor - Have an intelligence quotient (IQ) of =70, using the Kaufman Brief Intelligence Test, second edition (KBIT-2) Extension Phase: - Have completed all scheduled visits up to and including Visit 8 in the Core Study Randomization Phase Are the trial subjects under 18? yes Number of subjects for this age range: 132 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Core Study - With a diagnosis of primary generalized epilepsies or seizures such as absences and/or myoclonic epilepsies - Have current or a history of pseudo-seizures (psychogenic non-epileptic seizures [PNES]) within approximately 5 years prior to Visit 1 - Have a diagnosis of Lennox-Gastaut syndrome - Have seizure clusters where individual seizures cannot be counted - Have a history of status epilepticus that required hospitalization during the 12 months prior to the Visit 1 - Have an unstable psychiatric diagnosis that may confound the investigator’s ability to conduct the study or that may prevent completion of the protocol specified tests (eg, significant suicide risk, including suicidal behavior and ideation 6 months prior to Visit 1, current psychotic disorder, or acute mania) - Have any concomitant illnesses/co-morbidities (eg, autism, attention-deficit hyperactivity disorder [ADHD]) at Visit 1 that could severely affect cognitive function during the course of the study - Have previously participated in a clinical trial involving perampanel - Have chronically or routinely use benzodiazepines and who have not discontinued use at least 4 weeks prior to Visit 1 Extension phase - Those who, for any reason, discontinued early from the preceding double-blind study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the short-term effect of perampanel on cognition to placebo by using the Cognitive Drug Research (CDR) System when administered as an adjunctive therapy in adolescents (12 to less than 18 years of age) with inadequately controlled partial-onset seizures (with or without secondarily generalized seizures) ;Secondary Objective: - To assess the short-term effect of perampanel in adolescents on each of the CDR System 5 core cognitive domains of: Power of Attention, Continuity of Attention, Quality of Episodic Memory, Quality of Working Memory, and Speed of Memory To evaluate - the short- and long-term safety and tolerability of perampanel - the long-term effect of perampanel in adolescents on cognition by using the CDR System - the short- and long-term effects of perampanel on language by using the Controlled Oral Word Association Test - the short- and long-term effects of perampanel on visuomotor skills by using the Lafayette Grooved Pegboard Test - the long-term effect of perampanel on growth and development, including sexual development using Tanner Staging - the pharmacokinetics of perampanel using a population PK approach and to explore the PK/pharmacodynamic relationship - the efficacy of perampanel as determined by percent (%) change in seizure frequency and responder rate;Primary end point(s): Primary Safety Analysis - Cognitive Function: Change from baseline in the CDR System Global Cognition Score will be summarized by visit during the Randomization Phase and Extension Phase Part A. ;Timepoint(s) of evaluation of this end point: The primary endpoint of change from baseline in the CDR System Global Cognition Score at Week 19 will be analyzed using analysis of covariance (ANCOVA) with baseline (Visit 2) as a covariate, and region, gender and treatment as factors in the Full Analysis Set for cognition. If the Week 19 score is missing for a subject, the last non-missing score will be used in lieu of the Week 19 score for that subjec | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess the short-term effect of perampanel in adolescents on each of the CDR System 5 core cognitive domains of: Power of Attention, Continuity of Attention, Quality of Episodic Memory, Quality of Working Memory, and Speed of Memory. - To evaluate the short- and long-term safety and tolerability of perampanel in adolescents - To evaluate the long-term effect of perampanel in adolescents on cognition by using the CDR System - To evaluate the short- and long-term effects of perampanel in adolescents on language by using the Controlled Oral Word Association (COWAT) - To evaluate the short- and long-term effects of perampanel in adolescents on visuomotor skills by using the Lafayette Grooved Pegboard Test - To evaluate the long-term effect of perampanel on growth and development in adolescents, including sexual development using Tanner Staging - To evaluate the pharmacokinetics (PK) of perampanel in adolescents using a population PK approach and to explore the PK/pharmacodynamic (PD) relationship - To evaluate the efficacy of perampanel in adolescents as determined by percent (%) change in seizure frequency and responder rate;Timepoint(s) of evaluation of this end point: See protocol section 8.5.2.2 | — |
Countries
Australia, Belgium, Czech Republic, Hungary, India, Korea, Republic of, Latvia, Poland, Spain, Thailand, United States
Contacts
Public ContactCarol Shaw
Eisai Limited
Outcome results
None listed