An Open-Label, Multicenter Study With an Extension Phase to Evaluate the Safety, Tolerability, and Exposure-Efficacy Relationship of Perampanel Oral Suspension When Administered as an Adjunctive Therapy in Pediatric Subjects (Age 4 to Less Than 12 Years) With Inadequately Controlled Partial-Onset Seizures or Primary Generalized Tonic Clonic Seizures
Overview
- Phase
- Phase 3
- Intervention
- Perampanel
- Conditions
- Partial-Onset or Primary Generalized Tonic-Clonic Seizures
- Sponsor
- Eisai Inc.
- Enrollment
- 180
- Locations
- 4
- Primary Endpoint
- Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) for Total Group of Participants - Core Phase and Extension Phase A of This Study
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief 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.
Detailed Description
This is a multicenter, open-label, single-arm study in children (age 4 to \<12 years) with inadequately controlled POS or PGTC seizures. The study will consist of a Core Phase and two Extension Phases (Extension Phase A \[for all countries in the study\], and Extension Phase B \[available for participants enrolled in Japan and in countries where an extended access program {EAP} cannot be implemented, after completion of Extension Phase A\]). The Core Phase will consist of the following 2 phases: Pretreatment and Treatment Phase. The Pretreatment Phase, during which participants will be assessed for eligibility, will consist of up to a 4-weeks +/- 3 days Screening/Baseline Period. The Treatment Phase will consist of 3 periods: Titration Period (up to an 11-weeks: dose titration on the basis of individual clinical response and tolerability), Maintenance Period (up to a 12-weeks: continuation of perampanel oral suspension once daily at the dose level achieved at the end of the Titration Period), and Follow-up Period (up to 4-weeks +/- 7 days: only for those participants not entering into Extension Phase A or those who prematurely discontinue from the study). Extension Phase A will consist of up to 29-weeks Maintenance Period and up to 4-weeks +/- 7 days Follow-up Period after the last dose of perampanel only for participants who did not enter into Extension Phase B. All participants who complete all scheduled visits up to and including Visit 9 in the Treatment Phase will be eligible to participate in Extension Phase A of the study. During the Maintenance Period of Extension Phase A, all participants will continue with their optimal perampanel dose (that is, dose level that they complete on during the Core Phase). After completing Extension Phase A, participants in Japan and in countries where EAP cannot be implemented, participants will be eligible to participate in Extension Phase B. In Japan, treatment will continue as long as clinically appropriate according to the judgment of the investigator. However, treatment of participants in Extension B will be completed when the participant reaches 12 years of age or when perampanel is commercially available in Japan for treatment of POS in pediatric participants (4 to less than 12 years of age). In countries where an EAP cannot be implemented, participation in Extension B will continue as long as clinically appropriate according to the judgment of the investigator, until the participants reaches 12 years of age or perampanel oral suspension is commercially available.
Investigators
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
- •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
Arms & Interventions
Perampanel
Perampanel 0.5 milligrams per milliliter (mg/mL) oral suspension
Intervention: Perampanel
Outcomes
Primary Outcomes
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs) for Total Group of Participants - Core Phase and Extension Phase A of This Study
Time Frame: Baseline up to 4 weeks (follow up in Extension Phase A) after last dose of study drug in Extension Phase A at Week 52 (up to 56 weeks)
Percentage of Participants With Treatment Emergent Markedly Abnormal Laboratory Values for Total Group of Participants- Core Phase and Extension Phase A of This Study
Time Frame: Baseline up to 52 weeks
Percentage of Participants With Abnormal Vital Sign Values for Total Group of Participants- Core Phase and Extension Phase A of This Study
Time Frame: Baseline up to 52 weeks
Pre-defined criteria of vital signs abnormalities: maximum (max.) increase or decrease from baseline in sitting/supine systolic blood pressure (SBP) of greater than or equal to (\>=) 20 or 40 millimeter of mercury (mmHg); maximum increase or decrease from baseline in sitting/supine diastolic blood pressure (DBP) \>=10 or 20 mmHg; increase or decrease from baseline in pulse rate (number of heart beats per minute \[bpm\]) of \>=15 or 30 bpm. Data for this outcome measure has been assessed and reported till Week 52.
Percentage of Participants With Markedly Abnormal Electrocardiogram (ECG) Parameters for Total Group of Participants- Core Phase and Extension Phase A of This Study
Time Frame: Baseline up to 52 weeks
Secondary Outcomes
- Model Predicted Percent Change in Average Seizure Frequency Over 28 Days During Maintenance Period in Core Phase of This Study From Baseline- Assessed as Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel (518 ng/mL)(Baseline, Week 23)
- Overall Responder Probability For Non-Asian Participants With POS During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel(Baseline up to 23 weeks)
- Overall Responder Probability For Participants With PGTC Seizures During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel(Baseline up to 23 weeks)
- Number of Seizure Free Observations During Core Phase of This Study: Assessment Based on Relationship With Average Steady State Plasma Concentration (Cav, ss) of Perampanel(Baseline up to Week 23)
- Model Predicted Change From Baseline in Total Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel(Baseline up to Week 23)
- Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Participants Aged 4 to 5 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel(Baseline up to Week 23)
- Model Predicted Change From Baseline in Total Child Behavior Check List (CBCL) Score (Participants Aged Greater Than [>] 5 to <12 Years) During Core Phase of This Study: Assessment Based on Relationship With Plasma Levels of Perampanel(Baseline up to Week 23)
- Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Dominant Hand in Core Phase of This Study for All Participants Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanell(Baseline up to Week 23)
- Model Predicted Change From Baseline in Total Time to Complete LGPT Score for Non-dominant Hand in Core Phase of This Study for All Participants Aged 4 to <12 Years: Assessment Based on Relationship With Plasma Levels of Perampanel(Baseline up to Week 23)
- Percentage of Participants With Most Frequent Treatment Emergent Adverse Events (AEs) for Total Group of Participants That Were Considered Related to Perampanel- Core Phase of This Study(Baseline up to 23 weeks)
- Change From Baseline in Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) Score as Per Seizure Type at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study(Baseline, Week 23, Week 52)
- Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 1.5 to 5 Years) as Per Seizure Type at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study(Baseline, Week 23, Week 52)
- Change From Baseline in Total Child Behavior Check List (CBCL) Score (Age Group 6 to 18 Years) as Per Seizure Type at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study(Baseline, Week 23, Week 52)
- Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores for 8 Years and Under as Per Seizure Type at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study(Baseline, Week 23, Week 52)
- Change From Baseline in Time to Complete Lafayette Grooved Pegboard Test (LGPT) Scores Over 8 Years as Per Seizure Type at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study(Baseline, Week 23, Week 52)
- Change From Baseline in Height (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study(Baseline, Week 23, Week 52)
- Change From Baseline in Weight (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study(Baseline, Week 23, Week 52)
- Change From Baseline in Thyrotropin Value (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study(Baseline, Week 23, Week 52)
- Change From Baseline in Thyroxine, Free and Triiodothyronine, Free Values (Growth and Development Parameters) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study(Baseline, Week 23, Week 52)
- Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) Values (a Growth and Development Parameter) at Week 23 (Core Phase) and at Week 52 (Extension Phase A) of This Study(Baseline, Week 23, Week 52)
- Percentage of Participants With Change From Baseline in Markedly Abnormal Encephalogram (EEG) Parameter Values During Awake and Sleep State for Total Group of Participant: Core Phase and Extension Phase A of This Study(Baseline up to 52 weeks)
- Number of Encephalogram (EEG) Abnormalities During Awake and Sleep State for Total Group of Participant: Core Phase and Extension Phase A of This Study(Baseline up to 52 weeks)
- Percentage of Participants With Any Treatment-emergent Reports of Suicidal Ideation and Behavior Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)- Core Phase and Extension Phase A of This Study(Up to 52 weeks)
- Percentage of Participants With Shift From Baseline in Suicidal Ideation and Behaviors Assessed Using C-SSRS Scores to Extension Phase A (Week 52) of This Study(Up to 52 weeks)
- Median Percent Change in Seizure Frequency Per 28 Days During the Treatment Phase Relative to the Pretreatment Phase (Baseline)- Core Phase and Extension Phase A of This Study(Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52)
- Percentage of Participants Based on 25% Responder Rate- Core Phase and Extension Phase A of This Study(Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52)
- Percentage of Participants Based on 50% Responder Rate- Core Phase and Extension Phase A of This Study(Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52)
- Percentage of Participants Based on 75% Responder Rate- Core Phase and Extension Phase A of This Study(Baseline, Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52)
- Percentage of Participants Who Were Seizure-free- Core Phase and Extension Phase A of This Study(Weeks 1-13, Weeks 14-26, Weeks 27-39, Weeks 40-52)
- Percentage of Participants With Clinical Global Impression of Change Scores (CGIC)- Core Phase and Extension Phase A of This Study(Baseline, Week 23, Week 52)