Study to Evaluate the Efficacy and Safety of Perampanel as Monotherapy or First Adjunctive Therapy in Subjects With Partial Onset Seizures With or Without Secondarily Generalized Seizures or With Primary Generalized Tonic-Clonic Seizures
Condition: Partial Onset Seizures; Secondarily Generalized Seizures; Primary Generalized Tonic-Clonic Seizures
MeSH terms: Seizures
Intervention: Perampanel
Intervention description: film-coated tablets
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: monotherapy; adjunctive therapy; open-label; multicenter

Summary:

      This study will assess the retention rate of perampanel when given as monotherapy or first
      adjunctive therapy in participants with partial-onset seizures or primary generalized tonic
      clonic seizures. The study consists of 4 periods: a Screening Period (to start no earlier
      than 6 weeks before the first dose of study drug), a Titration Period (up to 13 weeks), a
      Maintenance Period (39 weeks), and a Follow-Up Period (4 weeks).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants will be male or female and no younger than 4 years of age and be able to
             swallow perampanel tablets.

          -  Participants must have a diagnosis of epilepsy with POS with or without SGS or with
             PGTCS. Either of the following must have occurred to support an epilepsy diagnosis:

               1. At least two unprovoked (or reflex) seizures occurring greater than 24 hours
                  apart

               2. One unprovoked (or reflex) seizure with Electroencephalography (EEG) evidence of
                  seizures

          -  Participants who receive perampanel as a first adjunctive therapy must currently have
             been treated with stable doses of monotherapy with an anti-epileptic drug (AED) for 8
             weeks prior to Visit 2 (Week 0), have not previously received adjunctive AED
             treatment, and must, in the investigator's judgement, be in need of initial adjunctive
             therapy after failure to control seizures with AED monotherapy, at the optimal dose
             and duration.

          -  Participants who receive perampanel as monotherapy, who were newly diagnosed
             (treatment naïve), following the defined diagnosis of epilepsy.

          -  Participants who are currently receiving monotherapy treatment may receive perampanel
             as monotherapy if, in the investigator's judgment, the participant may benefit from a
             change in monotherapy treatment. Participants must not have previously received
             adjunctive AED treatment.

          -  If antidepressants or antianxiety drugs are used, participants must be on a stable
             dose regimen of these drugs during the 8 weeks before Visit 2 (Week 0).

        Exclusion Criteria:

          -  Participants should not have previously received or currently be receiving perampanel.

          -  Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
             positive beta human chorionic gonadotropin [β-hCG] or 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:

               -  Within 28 days before study entry, did not use a highly effective method of
                  contraception, which includes any of the following:

                    -  Total abstinence (if it is their preferred and usual lifestyle)

                    -  An intrauterine device or intrauterine hormone-releasing system

                    -  An oral contraceptive (with additional barrier method if using contraceptive
                       containing levonorgestrel); participant must be on a stable dose of the same
                       oral contraceptive product for at least 28 days before dosing and throughout
                       the study and for 28 days after study drug discontinuation

                    -  Have a vasectomized partner with confirmed azoospermia

               -  Do not agree to use a highly effective method of contraception (as described
                  above) throughout the entire study period and for 28 days after study drug
                  discontinuation For sites outside of the European Union, it is permissible that
                  if a highly effective method of contraception is not appropriate or acceptable to
                  the participant, then the participant must agree to use a medically acceptable
                  method of contraception, i.e, double barrier methods of contraception such as
                  condom plus diaphragm or cervical/vault cap with spermicide.

        NOTE: All females will be considered to be of childbearing potential unless they are
        postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age
        group, and without other known or suspected cause) or have been sterilized surgically (i.e,
        bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery
        at least 1 month before dosing).

          -  Presence of or previous history of Lennox-Gastaut syndrome

          -  Presence of non-motor simple partial seizures only

          -  A history of status epilepticus within 1 year before Screening Visit (Visit 1)

          -  Participants on antipsychotics or who have psychotic disorder(s) or unstable recurrent
             affective disorder(s) with a history of attempted suicide within 1 year before
             Screening Visit (Visit 1)

          -  Presence of a progressive central nervous system (CNS) disease, including degenerative
             CNS diseases and progressive tumors

          -  Concomitant use of barbiturates (except for seizure control indication and
             premedication for electroencephalogram) and benzodiazepines (except for seizure
             control indication) within 8 weeks prior to Visit 2 (Week 0)

          -  Use of intermittent rescue benzodiazepines (i.e, 1 to 2 doses over a 24-hour period is
             considered a one time rescue) 2 or more times in the 8-week period prior to Visit 2
             (Week 0)

          -  Severe renal insufficiency (defined by estimated glomerular filtration rate of < 30
             milliliters per minute [mL/min]) or participants who receive hemodialysis

          -  Evidence of clinically significant disease (eg, cardiac, respiratory,
             gastrointestinal, renal disease, hepatic disease) that in the opinion of the
             investigator(s) could affect the participant's safety or study conduct NOTE: Stable
             elevation of liver enzymes, alanine aminotransferase and aspartate aminotransferase
             due to concomitant medication(s) will be allowed if they are less than 3 times the
             upper limits of normal.

          -  Hypersensitivity to perampanel or any excipients

          -  Participants with rare hereditary problems of galactose intolerance, the Lapp lactase
             deficiency or glucose-galactose malabsorption

          -  Participants who are participating in other interventional clinical trial

          -  Participant who are judged to have inadequate cognitive ability for participation in
             the study (intelligence quotient < 80 or investigator judgment)

          -  Any suicidal ideation with intent with or without a plan, at the time of or within 6
             months of screening, as indicated by answering "Yes" to questions 4 and 5 on the
             Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS)

          -  Any lifetime suicidal behavior based on the C-SSRS

          -  Concomitant use of any form of cannabidiol (CBD)

          -  Planned brain surgery during study participation