Perampanel as Adjunctive Therapy in Pediatrics With Partial Onset Seizures or Primary Generalized Tonic Clonic Seizures
Condition: Partial-Onset or Primary Generalized Tonic-Clonic Seizures
MeSH terms: Seizures
Intervention: Perampanel
Intervention description: E2007
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 180.0
Sex: All
Minimum age: 4 Years
Maximum age: 12 Years
Healthy volunteers: No
Keywords: Partial-Onset Seizures; Primary Generalized Tonic-Clonic Seizures; Adjunctive Therapy; Epilepsy

Summary:

      This is an open-label, multicenter study with an Extension Phase to evaluate the safety and
      tolerability of perampanel oral suspension when administered as an adjunctive therapy in
      children (ages 4 to less than [<] 12 years) with inadequately controlled partial onset
      seizures (POS) or primary generalized tonic clonic (PGTC) seizures.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a diagnosis of epilepsy with POS with or without secondarily generalized (SG)
             seizures or PGTC seizures according to the International League Against Epilepsy's
             (ILAE) Classification of Epileptic Seizures (1981). A diagnosis should have been
             established at least 6 months prior to Visit 1 by clinical history and an
             electroencephalogram (EEG) that is consistent with the diagnosis; normal interictal
             EEGs will be allowed provided that the participant meets the other diagnosis criterion
             (that is, clinical history)

          -  Male or female participant, from age 4 to <12 years at the time of informed
             consent/assent

          -  Have a minimum weight of 16 kilograms (kg) (35 pounds [lb])

          -  Have had a brain imaging (example, magnetic resonance imaging [MRI] scan or computed
             tomography [CT] before Visit 1 that ruled out a progressive cause of epilepsy)

          -  During the 12 weeks +/- 3 days (4 weeks +/- 3 days in Japan only) prior to Visit 2,
             participants must have equal or greater than (=>) one POS or one PGTC seizure. Only
             simple POS with motor signs, complex POS, and complex POS with secondary
             generalization are counted toward this inclusion for POS

          -  Are currently being treated with stable doses of 1 to a maximum of 3 approved
             antiepileptic drugs (AEDs). Doses must be stable for at least 4 weeks before to Visit
             1; in the case where a new AED regimen has been initiated for a participant, the dose
             must be stable for at least 8 weeks prior to Visit 1. Only one EIAED (defined as
             carbamazepine, phenytoin, oxcarbazepine, or eslicarbazepine) out of the maximum of
             three AEDs is allowed (A vagal nerve stimulator [VNS] will be counted as one of the 3
             allowed AEDs)

        Exclusion Criteria:

          -  Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
             positive beta human chorionic gonadotropin [β-hCG] or human chorionic gonadotropin
             [hCG] test with a minimum sensitivity of 25 International Units per liter [IU/L] or
             equivalent units of β-hCG or hCG). A separate baseline assessment is required if a
             negative screening pregnancy test was obtained more than 72 hours before the first
             dose of study drug

          -  Females of childbearing potential who:

               -  Had unprotected sexual intercourse within 30 days before study entry and who do
                  not agree to use a highly effective method of contraception (example, total
                  abstinence, an intrauterine device, a contraceptive implant, an oral
                  contraceptive, or have a vasectomized partner with confirmed azoospermia)
                  throughout the entire study period or for 28 days after study drug
                  discontinuation. If a highly effective method is not appropriate or acceptable
                  for the participant, then the participant may use a medically effective method
                  (example, a double barrier method such as condom plus diaphragm with spermicide)

               -  Are currently abstinent, and do not agree to use a double-barrier method (as
                  described above) or refrain from being sexually active during the study period or
                  for 28 days after study drug discontinuation

               -  Are using hormonal contraceptives but are not on a stable dose of the same
                  hormonal contraceptive product for at least 4 weeks before dosing and who do not
                  agree to use the same contraceptive during the study or for 28 days after study
                  drug discontinuation

          -  Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within
             approximately 5 years before Visit 1

          -  Have a history of status epilepticus that required hospitalization during the 6 months
             before Visit 1

          -  Have an unstable psychiatric diagnosis that may confound participants' ability to
             participate in the study or that may prevent completion of the protocol-specified
             tests (example, significant suicide risk, including suicidal behavior and ideation
             within 6 months before Visit 1, current psychotic disorder, acute mania)

          -  Any suicidal ideation with intent with or without a plan within 6 months before Visit
             2 (that is, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of
             the Columbia Suicide Severity Rating Scale [C-SSRS]) in participants aged 6 and above

          -  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

          -  Evidence of clinically significant disease (example, cardiac, respiratory,
             gastrointestinal, renal disease) that in the opinion of the investigator(s) could
             affect the participant's safety or interfere with the study assessments

          -  Evidence of moderate or severe renal insufficiency as defined by estimated glomerular
             filtration rates (eGFRs) of 31 to <60 milliliters per minute (mL/min) and <30 mL/min,
             respectively

          -  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)

          -  Evidence of significant active hematological disease; white blood cell (WBC) count
             equal or less than (=<) 2500 per (/) microliter (µL) (2.50 1 constant [E]+09/liter
             [L]) or an absolute neutrophil count =<1000/µL (1.00 1E+09/L)

          -  Clinically significant electrocardiogram (ECG) abnormality, including prolonged
             corrected QT interval (QTc) defined as greater than (>) 450 milliseconds (msec)

          -  Have a progressive central nervous system (CNS) disease, including degenerative CNS
             diseases and progressive tumors

          -  Multiple drug allergies or a severe drug reaction to an AED(s), including
             dermatological (example, Stevens Johnson syndrome), hematological, or organ toxicity
             reactions.

          -  Concomitant use of felbamate as an AED for <2 years or where the dose has not been
             stable for at least 8 weeks before Visit 1. Participants must not have a history of
             WBC count =<2500/µL, platelets below 100,000, liver function tests (LFTs) above 3
             times the 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 before Visit 1 to be eligible for study participation

          -  Concomitant use of vigabatrin: participants who took vigabatrin in the past must be
             off vigabatrin for at least 5 months before Visit 1 and with documentation showing no
             evidence of a vigabatrin-associated clinically significant abnormality in a visual
             perimetry test

          -  Concomitant use of cannabinoids

          -  Used benzodiazepines for epilepsy during which the dose has not been stable for >4
             weeks prior to Visit 1. Benzodiazepines use as rescue medication for seizure control
             is allowed; however, intermittent use of benzodiazepines for any other indication
             (example, anxiety/sleep disorders) is prohibited

          -  A VNS implanted <5 months before Visit 1 or changes in parameter <4 weeks before Visit
             1 (or thereafter during the study)

          -  On a ketogenic diet for which the diet is not a stable regimen for at least 4 weeks
             before Visit 1

          -  History of or a concomitant medical condition that in the opinion of the
             investigator(s) would preclude the participant's participation in a clinical study or
             compromise the participant's ability to safely complete the study

          -  Have previously been exposed to perampanel in a clinical trial or by prescription for
             more than 2 months or discontinued for Adverse Events (AEs)

          -  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

          -  Participants with rare hereditary problems of galactose intolerance, the Lapp lactase
             deficiency or glucose-galactose malabsorption