Pharmacokinetics, Efficacy, and Safety of Perampanel Oral Suspension on Seizure Frequency in Pediatric Subjects Maintained on One to Three Stable Antiepileptic Drugs
Condition: Central Nervous System
Intervention: perampanel
Intervention description: During the titration period, participants started at a set daily dose of 0.015 mg/kg and had doses up-titrated at 1-week intervals (6 titration steps) to a maximum daily dose of 0.18 mg/kg. During the Maintenance Period, participants continued taking perampanel oral suspension once daily at the dose level they achieved at the end of the Titration Period. During the extension phase, participants continued taking perampanel oral suspension once daily, at the dose level achieved at the end of the treatment phase of the core study to a maximum daily dose of 0.18 mg/kg. The maximum total daily dose a participant was allowed was 12 mg.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 2 Years
Maximum age: 11 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        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