Pharmacokinetic Study With an Oral Suspension of Perampanel as Adjunctive Therapy in Pediatric Subjects With Epilepsy
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: perampanel
Intervention description: oral suspension.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 1 Month
Maximum age: 4 Years
Healthy volunteers: No
Keywords: epilepsy; refractory partial seizures

Summary:

      The purpose of this study is to evaluate the pharmacokinetics (PK) of perampanel during the
      Maintenance Period of the Core Study following oral suspension administration given as an
      adjunctive therapy in pediatric participants from 1 month to less than 4 years of age with
      epilepsy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, from 1 month to less than 4 years of age (and of at least 36 weeks
             gestational age) at the time of consent

          -  Have a minimum weight of 4 kilograms (kg) (8.8 pounds [lb])

          -  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 2 weeks (≤6 months of age) or 4 weeks
             (>6 months of age) before 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)

          -  Have had brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI])
             before Visit 1 that ruled out a progressive cause of epilepsy

          -  Have had 1 or more seizure(s) before Visit 1

          -  Currently being treated with a stable dose (i.e., unchanged for at least 5 half-lives)
             of 1 to a maximum of 4 antiepileptic drugs (AEDs) (at least 6, but not more than 8, in
             the age group of 1 to less than 24 months, and up to 13 subjects in the age group of 2
             to less than 4 years, will be taking 1 EIAEDs [that is, carbamazepine (CBZ),
             oxcarbazepine (OXC), phenytoin (PHT), or eslicarbazepine (ESL)] out of the maximum of
             4 AEDs. The remaining participants cannot be taking any EIAEDs).

          -  Have been on their current concomitant AED(s) with a stable dose for at least 2 weeks
             or 5 half-lives, whichever is longer, before Visit 1

          -  Must have discontinued all restricted medications (example, medications known to be
             inducers of cytochrome P450 3A) at least 2 weeks or 5 half-lives (whichever is longer)
             before Visit 1

          -  If entering the Extension Phase, must have completed the last visit of the Maintenance
             Period of the Core Study

        Exclusion Criteria:

          -  Have a history of status epilepticus that required hospitalization during the 3 months
             before Visit 1

          -  Have seizures due to treatable medical conditions, such as those arising due to
             metabolic disturbances, toxic exposure, or an active infection

          -  Have epilepsy secondary to progressive central nervous system (CNS) disease or any
             other progressive neurodegenerative disease, including tumors

          -  Have had epilepsy surgery within 1 year of Visit 1

          -  Are scheduled and/or confirmed to have epilepsy surgery within 6 months after Visit 1

          -  Used intermittent rescue benzodiazepines (i.e., 1 to 2 doses over a 24-hour period
             considered one-time rescue) 2 or more times in the 2 weeks before Visit 1

          -  Current use of felbamate, or any evidence of ongoing hepatic or bone marrow
             dysfunction associated with prior felbamate treatment. (Prior use of felbamate must be
             discontinued at least 8 weeks before Visit 1.)

          -  Current use of vigabatrin or any evidence of clinically significant vision abnormality
             associated with prior vigabatrin treatment. (Prior use of vigabatrin must be
             discontinued at least 2 weeks before Visit 1.)

          -  Are on ketogenic diet regimen that has not been stable for at least 4 weeks before
             Visit 1

          -  Concomitant use of other drugs known to influence the CNS, (other than AEDs for
             epilepsy), where the dose has not been stabilized for at least 5 half-lives or 2
             weeks, whichever is longer, before Visit 1

          -  Have any concomitant illnesses/co-morbidities that could severely affect the
             participant's safety or study conduct

          -  Have evidence of clinically significant disease (e.g., cardiac, respiratory,
             gastrointestinal, renal disease) that in the opinion of the investigator(s) could
             affect the participant's safety or study conduct

          -  Have clinically significant laboratory abnormalities or any clinically acute or
             chronic disease

          -  Have evidence of significant active hepatic disease. Stable elevation of liver
             enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) due to
             concomitant medication(s), will be allowed if they are less than 3 times the upper
             limit of normal (ULN)

          -  Have clinical evidence of significant active hematological disease; white blood cell
             (WBC) count ≤2500/ microliter (μL) (2.50 x 10^9/Liter [L]) or an absolute neutrophil
             count ≤1000/μL (1.00 x 10^9/L)

          -  Have conditions that may interfere with their participation in the study and/or with
             the PK of study drug

          -  Have participated in a study involving administration of an investigational drug or
             device within 4 weeks before Visit 1, or within approximately 5 half-lives of the
             previous investigational compound, whichever is longer

          -  Have recently (within 30 days before Visit 1) been exposed to perampanel in a clinical
             study or by prescription, and/or previous discontinuation from perampanel treatment
             due to adverse events related to perampanel

          -  Have a clinically significant ECG abnormality, including prolonged corrected QT
             interval (QTc) defined as >450 milliseconds (msec)

          -  Have had multiple drug allergies or a severe drug reaction to an AED(s), including
             dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity
             reactions