A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial With an Open-Label Extension Phase of Perampanel as Adjunctive Treatment in Subjects at Least 2 Years of Age With Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome
Overview
- Phase
- Phase 3
- Intervention
- Perampanel
- Conditions
- Lennox-Gastaut Syndrome (LGS)
- Sponsor
- Eisai Inc.
- Enrollment
- 101
- Locations
- 65
- Primary Endpoint
- Core Study Phase: Median Percent Change in Drop Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
This study is being conducted to demonstrate that perampanel given as adjunctive anti-epileptic treatment is superior to placebo in reducing the number of drop seizures in participants with inadequately controlled seizures associated with Lennox-Gastaut Syndrome (LGS).
Detailed Description
This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group study of perampanel as adjunctive therapy in participants with inadequately controlled seizures associated with LGS. The study will consist of 3 phases: Prerandomization (4 to 8 weeks), Randomization (18 weeks), and an Extension A (52 weeks). An additional Extension B with open-label treatment will be available for optional participation to participants who reside in Japan and in countries where an expanded access program (EAP) cannot be implemented or has not yet been implemented.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants must have a diagnosis of LGS as evidenced by:
- •more than one type of generalized seizure, including drop seizures (atonic, tonic, or myoclonic) for at least 6 months before Visit 1;
- •an electroencephalogram (EEG) reporting diagnostic criteria for LGS at some point in their history (abnormal background activity accompanied by slow, spike, and wave pattern \<2.5 hertz \[Hz\]).
- •Participants must be at least 2 years old at the time of consent/assent
- •Participants must have been \<11 years old at the onset of LGS
- •Participants must have experienced an average of at least 2 drop seizures per week in the 4-week Baseline Period preceding randomization
- •Participants must have been receiving 1 to 4 concomitant antiepileptic drugs (AEDs) at a stable dose for at least 30 days before Visit 1 (vagal nerve stimulation (VNS) and ketogenic diet do not count as AEDs). Use of cannabidiol (CBD) products is allowed and is counted as one of the 4 maximum allowed concomitant AEDs. CBD dose and product must have remained stable for at least 30 days before Visit 1 and is to remain the same throughout the course of the Core Study
- •In the investigator's opinion, parents or caregivers must be able to keep accurate seizure diaries
- •Body weight at least 8 kilogram (kg)
Exclusion Criteria
- •Presence of progressive neurological disease
- •Presence of drop seizure clusters where individual seizures cannot be reliably counted (seizure clusters are defined as ≥2 drop seizures with \<5 minutes between any 2 consecutive seizures)
- •Prior treatment with perampanel with discontinuation due to safety issues (related to perampanel)
- •Prior treatment with perampanel within 30 days before Visit 1
- •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
- •Scheduled for epilepsy-related surgery or any other form of surgery during the projected course of the study
- •Ketogenic diet and VNS, unless stable and ongoing for at least 30 days before Visit 1
- •Treatment with an investigational drug or device within 30 days before Visit 1
- •Status epilepticus within 12 weeks of Visit 1
- •If felbamate is used as a concomitant AED, participants must be on felbamate for at least 1 year, with a stable dose for 60 days before Visit
Arms & Interventions
Perampanel up to 8 mg/day
During the Randomization Phase, participants will receive perampanel at a starting dose of 2 milligrams per day (mg/day). Thereafter, the dose will be increased to a maximum target dose of 8 mg/day according to individual tolerability and efficacy for up to 18 weeks. Participants who enter into Extension A will continue to receive perampanel at the dose last received during randomization phase. Participants can be titrated up to 12 mg/day (at 2-week intervals) per the investigator's discretion. Participants who continue in Extension B will continue to receive perampanel at the dose last received at the end of Extension A.
Intervention: Perampanel
Matching placebo
During the Randomization Phase, participants will receive matching placebo for up to 18 weeks. During the Extension A, participants who received placebo during the Randomization Phase will begin treatment with perampanel in a blinded manner in double-blind Conversion Period, starting at 2 mg/day and then up-titrated to a maximum target dose of 8 mg/day according to individual tolerability and efficacy. After the Conversion Period, participants can be titrated up to 12 mg/day (at 2-week intervals) per the investigator's discretion.
Intervention: Placebo
Matching placebo
During the Randomization Phase, participants will receive matching placebo for up to 18 weeks. During the Extension A, participants who received placebo during the Randomization Phase will begin treatment with perampanel in a blinded manner in double-blind Conversion Period, starting at 2 mg/day and then up-titrated to a maximum target dose of 8 mg/day according to individual tolerability and efficacy. After the Conversion Period, participants can be titrated up to 12 mg/day (at 2-week intervals) per the investigator's discretion.
Intervention: Perampanel
Outcomes
Primary Outcomes
Core Study Phase: Median Percent Change in Drop Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)
Time Frame: Baseline up to 18 weeks
Drop seizure was defined as a drop attack or spell involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the participant's position at the time of the attack or spell. Seizure frequency was based on the number of drop seizures per 28 days, calculated as the number of drop seizures over the entire time interval divided by the number of days in the interval and multiplied by 28.
Secondary Outcomes
- Core Study Phase: Percentage of Participants With 75% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures(Baseline up to 18 weeks)
- Core Study Phase: Percentage of Participants With 100% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures, Non-drop Seizures and Total Seizures(Baseline up to 18 weeks)
- Core Study Phase: Median Percent Change in Total Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)(Baseline up to 18 weeks)
- Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Drop Seizures(Baseline up to 18 weeks)
- Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Total Seizures(Baseline up to 18 weeks)
- Core Study Phase: Median Percent Change in Non-drop Seizure Frequency Per 28 Days During Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline)(Baseline up to 18 weeks)
- Core Study Phase: Percentage of Participants With 50% Response in the Maintenance Period of the Double-blind Treatment Phase Relative to the Prerandomization Phase (Baseline) for Non-drop Seizures(Baseline up to 18 weeks)
- Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase(Baseline up to 18 weeks)
- Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks))
- Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values(From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks))
- Number of Participants With Clinically Significant Vital Signs(From the date of the first administration of the study drug up to 28 days after the last dose of the study drug (up to 192 weeks))
- Core Study Phase: Model Predicted Average Perampanel Concentrations at Steady State (Cav,ss) During the Maintenance Period of Core Study Phase(Up to Week 18)