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

Study Overview
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Brief Summary
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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).

Official Title
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Multicenter, Open-Label 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

Conditions
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Partial Onset Seizures, Secondarily Generalized Seizures, Primary Generalized Tonic-Clonic Seizures

Intervention / Treatment
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* Drug: Perampanel


Participation Criteria
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Eligibility Criteria
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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: At least two unprovoked (or reflex) seizures occurring greater than 24 hours apart 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

Ages Eligible for Study
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Minimum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perampanel<br>Perampanel will be administered orally once daily (QD) at bedtime. At the beginning of the Titration Period, oral perampanel will start at a dose of 2 milligrams (mg) QD. Doses of perampanel will then be up titrated in increments of 2 mg at no less than 2-week intervals according to the investigator's judgment. At the 4 mg dose, the investigator will confirm whether further dose escalation is needed based on participant response and tolerability. The investigator may adjust dosing further or leave the participant at 4 mg. The maximum dose is 12 mg. During the 39-week Maintenance Period, participants will continue to receive the perampanel dose level that was administered at the end of the Titration Period. | Drug: Perampanel<br>* film-coated tablets<br>* Other names: E2007;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Remaining on Perampanel Treatment at 3 Months After the Initiation of Treatment | The retention rate was defined as the percentage of participants remaining on perampanel treatment at 3 months after the initiation of treatment. | Month 3 | 
| Percentage of Participants Remaining on Perampanel Treatment at 6 Months After the Initiation of Treatment | The retention rate was defined as the percentage of participants remaining on perampanel treatment at 6 months after the initiation of treatment. | Month 6 | 
| Percentage of Participants Remaining on Perampanel Treatment at 9 Months After the Initiation of Treatment | The retention rate was defined as the percentage of participants remaining on perampanel treatment at 9 months after the initiation of treatment. | Month 9 | 
| Percentage of Participants Remaining on Perampanel Treatment at 12 Months After the Initiation of Treatment | The retention rate was defined as the percentage of participants remaining on perampanel treatment at 12 months after the initiation of treatment. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Seizure-free Status During the Maintenance Period | Seizure-free status was defined as no incidence of seizure during the entire maintenance period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participants does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately. | Up to 39 weeks of Maintenance Period | 
| Percentage of Participants Who Achieved 3-month Seizure-free Status During the Maintenance Period | Seizure-free status was defined as no incidence of seizure at 3 months during the Maintenance Period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participant does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately. | Up to 3 months of Maintenance Period | 
| Percentage of Participants Who Achieved 6-month Seizure-free Status During the Maintenance Period | Seizure-free status was defined as no incidence of seizure at 6 months during Maintenance Period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: participant does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: participant loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately. | Up to 6 months of Maintenance Period | 
| Percentage of Participants Who Received Perampanel as a First Adjunctive Therapy and Converted to Perampanel Monotherapy | Percentage of participants who received perampanel as a first adjunctive therapy and converted to perampanel monotherapy were reported. | Up to 52 weeks | 
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | A TEAE was defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. | From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks) | 
| Number of Participants With Treatment-emergent Serious Adverse Events (SAE) | A SAE was defined as any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect. A TEAE was defined as an event that emerges during treatment having been absent pre-treatment, or worsens relative to the pre-treatment state. | From date of first administration of study drug up to 28 days after last dose of study drug (up to 56 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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monotherapy, adjunctive therapy, open-label, multicenter