Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome

Browse trials for

• Seizures 881
• Lennox Gastaut Syndrome 64
• Syndrome 9,221

Keywords

• Lennox-Gastaut Syndrome (LGS)
• Inadequately controlled seizures

Seizures

881 studies on the registry are indexed under Seizures; 144 are open to participants now.

This study's enrollment of 101 is above the median of 64 across 610 interventional studies indexed under Seizures.

Lead sponsor

Eisai Inc. is the lead sponsor of 360 studies on the registry; 7 are open to participants now.

Of its 81 completed or terminated interventional studies of FDA-regulated products, 54 (67%) have results posted.

Study arms

• Experimental
  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.

  Drug: Perampanel

• Placebo comparator
  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.

  Drug: Placebo · Drug: Perampanel

Interventions

• DrugPlacebo

  Participants will receive matching placebo in Randomization phase.

• DrugPerampanel

  Participants will receive perampanel in Randomization phase, open-label Extension A, and open-label Extension B.

  Also known as: E2007

Primary outcomes

1. Core Study Phase: Median Percent Change in Drop Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)

   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.

   Time frame: Baseline up to 18 weeks

Secondary outcomes

1. Core Study Phase: Median Percent Change in Total Seizure Frequency Per 28 Days During Double-blind Treatment Relative to the Prerandomization Phase (Baseline)

   Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries were used to collect seizure counts and types. 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.

   Time frame: Baseline up to 18 weeks

2. 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

   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. A responder was a participant who experienced a 50% or greater reduction in drop seizure frequency per 28 days during Maintenance from prerandomization.

   Time frame: Baseline up to 18 weeks

3. 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

   Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries was used to collect seizure counts and types. A responder was a participant who experienced a 50% or greater reduction in drop seizure frequency per 28 days during Maintenance from prerandomization.

   Time frame: Baseline up to 18 weeks

4. 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)

   Non-drop seizures were defined as non-drop attacks or spells. Drop attacks and spells involved the entire body, trunk, or head and lead to a fall, injury, slumping in a chair, or the participant's head hitting a surface, or could lead 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.

   Time frame: Baseline up to 18 weeks

5. 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

   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. Non-drop seizures were defined as non-drop attacks or spells. Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries were used to collect seizure counts and types. A responder was a participant who experienced a 75% or greater reduction in drop seizure/non-drop seizure/ frequency per 28 days during Maintenance from prerandomization.

   Time frame: Baseline up to 18 weeks

6. 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

   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. Non-drop seizures were defined as non-drop attacks or spells. Total seizure was the number of seizures assessed and recorded by the participant's parent/caregiver in the participant seizure diary. Seizure diaries was used to collect seizure counts and types. A responder was a participant who experienced a 100% or greater reduction in drop seizure/non-drop seizure/ frequency per 28 days during Maintenance from prerandomization.

   Time frame: Baseline up to 18 weeks

7. 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

   Non-drop seizures were defined as non-drop attacks or spells. Drop attacks and spells involved the entire body, trunk, or head and lead to a fall, injury, slumping in a chair, or the participant's head hitting a surface, or could lead to a fall or injury, depending on the participant's position at the time of the attack or spell. A responder was a participant who experienced a 50% or greater reduction in non-drop seizure frequency per 28 days during Maintenance from prerandomization.

   Time frame: Baseline up to 18 weeks

8. Core Study Phase: Percentage of Participants With Clinical Global Impression of Change Scores (CGIC) in the Double-blind Treatment Phase

   Assessment of disease severity utilized the CGIC scale at end of treatment to evaluate participants change in disease status from baseline. The CGIC is a 7-point likert scale that measures a physician's global impression of a participants clinical condition. Scale ranged from 1 to 7 with lower score indicated improvement (1=very much improved, 2=much improved, 3=minimally improved), higher score indicated worsening (5=minimally worse, 6= much worse, 7=very much worse), and a score of 4 indicated no change.

   Time frame: Baseline up to 18 weeks

9. Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

   A TEAE was defined as an adverse event with an onset date, or a worsening in severity from baseline (pre-treatment), on or after the first dose of study drug up to 28 days following study drug discontinuation. An AE was defined as any untoward medical occurrence in a participant or clinical investigation in a participant administered an investigational product. An AE does not necessarily have a causal relationship with a medicinal product. A serious adverse event (SAE) was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.

   Time frame: 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)

10. Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values

    Treatment-emergent markedly abnormal value for laboratory values was based Common Terminology Criteria for Adverse events (CTCAE) Version 4.0, and determined as if the post baseline CTCAE Version 4.0 grade increases from baseline and the post baseline grade was \>=2 (\>=3 for phosphate). Laboratory tests included: Hematology count with differential, Chemistry (Electrolytes, Liver function tests, Renal function parameters, Other: albumin, calcium, cholesterol, globulin, glucose, lactate dehydrogenase, phosphorus, total protein, lipid panel, uric acid), Urinalysis, and Viral tests (Hepatitis B surface antigen, Hepatitis C).

    Time frame: 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)

11. Number of Participants With Clinically Significant Vital Signs

    Clinically significant means that a value must have met both the criterion value and satisfied the magnitude of change relative to baseline. Vital sign parameters included systolic blood pressure (BP), diastolic BP, pulse rate.

    Time frame: 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)

12. Core Study Phase: Model Predicted Average Perampanel Concentrations at Steady State (Cav,ss) During the Maintenance Period of Core Study Phase

    Due to the early termination of the study resulting in reduced sample size and the variability in treatment response, population pharmacokinetic (PK) analysis and population pharmacokinetic/pharmacodynamic (PK/PD) modeling planned for this study were not conducted and hence data was not collected and analyzed for this outcome measure.

    Time frame: Up to Week 18

Baseline characteristics

Publications

• Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021 Apr 7;4(4):CD003277. doi: 10.1002/14651858.CD003277.pub4. PubMed 33825230 ↗

Study documents

• Study protocol · Nov 19, 2018
• Statistical analysis plan · Aug 16, 2021

Documents are hosted by the registry — open the source record to download them.