Pharmacokinetics, Efficacy, and Safety of Perampanel Oral Suspension on Seizure Frequency in Pediatric Subjects Maintained on One to Three Stable Antiepileptic Drugs

An Open-label Pilot Study With an Extension Phase to Evaluate the Pharmacokinetics, and to Generate Preliminary Safety, Tolerability, and Efficacy of Perampanel (E2007) Oral Suspension When Given as an Adjunctive Therapy in Pediatric Subjects From 2 to Less Than 12 Years of Age With Epilepsy

This study is designed to evaluate the pharmacokinetics, efficacy, and safety of perampanel oral suspension on seizure frequency in pediatric participants maintained on one to three stable antiepileptic drugs

This is a multicenter, multiple ascending dose, open-label study (Core Study) with an Extension Phase. The Core Study consisted of 2 phases, the Pretreatment Phase and the Treatment Phase. The Pretreatment Phase lasted up to 2 weeks in duration, during which participants were assessed for their eligibility to participate in the study. The Treatment Phase consisted of 3 periods: Titration (7 weeks), Maintenance (4 weeks), and Follow-up (4 weeks; only for those participants not rolling over into the Extension Phase after completing the Treatment Phase and for those participants who discontinued from the study). All subjects who completed all scheduled visits up to and including the final visit of the Treatment Phase (Core Study) were eligible to participate in the Extension Phase of the study. The Extension Phase consisted of 2 periods: Maintenance (41 weeks) and Follow-up (4 weeks).

Inclusion:

1. Have a minimum weight of 10 kg (22 lb)
2. Have had brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) prior to Visit 1 that ruled out a progressive cause of epilepsy
3. Have a diagnosis of epilepsy with any type of seizure 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 electroencephalogram (EEG) that is consistent with epilepsy; normal interictal EEGs will be allowed provided that the participant meets the other diagnosis criterion (i.e. clinical history)
4. Have had one or more seizure(s) during the 4 weeks prior to Visit 1
5. Are currently being treated with stable doses of one to a maximum of three AEDs for at least 4 weeks prior to Visit 1 and throughout the study duration (Only one perampanel inducing AED [i.e. carbamazepine, oxcarbazepine, phenytoin] out of the maximum of 3 AEDs is allowed in at least one third of the participants in each age cohort and not to exceed one half of the population of each age cohort. The remaining participants should not be taking any inducer)
6. Have been on their current concomitant AED regimen for 2 months or more with a stable dose for at least 4 weeks prior to Visit 1
7. Must have discontinued all restricted medications at least 2 weeks or five half-lives (whichever is longer) prior to Visit 1
8. Females aged at least 8 years or of child-bearing potential must have a negative serum beta-hCG at Visit 1 and a negative urine pregnancy test prior to titration at Visit 2. Female participants 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 drug to be abstinent or commit to the consistent and correct use of a medically acceptable method of birth control (e.g., a double-barrier method [condom + spermicide, condom + diaphragm with spermicide])

Exclusion:

1. Have a history of status epilepticus that required hospitalization during the 6 months prior to Visit 1
2. Have current or a history of pseudo-seizures (psychogenic non-epileptic seizures [PNES]) from birth or within approximately 5 years prior to Visit 1
3. Have seizures due to treatable medical conditions, such as those arising due to metabolic disturbances, toxic exposure, or an active infection
4. Have epilepsy secondary to progressive cerebral disease or any other progressive neurodegenerative disease
5. Have had epilepsy surgery within 1 year prior to Visit 1
6. Are scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit 1; however, those who have previously documented failed epilepsy surgery will be allowed
7. Use of intermittent rescue benzodiazepines (i.e. 1-2 doses over a 24-hour period considered one-time rescue) two or more times in a 30-day period prior to Visit 1
8. If felbamate is used as a concomitant AED, participants must be on felbamate for at least 2 years, with a stable dose for 8 weeks prior to Visit 1. They must not have a history of white blood cell (WBC) count below 2500/L (2.50 x 10^9/L), platelets below 100,000, liver function tests (LFTs) above 3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate. If participants received felbamate in the past, it must have been discontinued 8 weeks prior to Visit 1
9. Have concomitant use of vigabatrin: participants who took vigabatrin in the past must be off vigabatrin for approximately 5 months prior to Visit 1 and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in the visual perimetry test
10. If ketogenic diet is used, participants must be on a stable regimen for at least 4 weeks prior to Visit 1
11. Have previously participated in a clinical trial involving perampanel