Phase 3
N=163
A Efficacy and Safety Study of Adjunctive Perampanel in Primary Generalized Tonic Clonic Seizures
Seizure Disorder Generalized Tonic Clonic
Bottom Line
View on ClinicalTrials.gov: NCT01393743 ↗Enrolled (actual)
163
Serious AEs
10.3%
Results posted
Jan 2016
Primary outcome: Primary: Median Percent Change in Primary Generalized Tonic Clonic Seizure Frequency (PGTC) Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study) — -38.38; -76.47 Percent change — p=0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Perampanel (Drug); Placebo comparator (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Eisai Inc.
- Primary completion
- May 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Median Percent Change in Primary Generalized Tonic Clonic Seizure Frequency (PGTC) Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study) |
-38.38; -76.47 | 0.0001 sig |
| PRIMARY 50% Responder Rate for Primary Generalized Tonic Clonic Seizure During Maintenance - LOCF - (for Core Study) |
39.5; 64.2 | 0.0019 sig |
| PRIMARY 50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) |
55.1; 74.6; 75.9; 78.4; 78.1; 79.8 | — |
| SECONDARY Median Percent Change in All Seizure Frequency Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study) |
-22.87; -43.4 | 0.0018 sig |
| SECONDARY Median Percent Change in Primary Generalized Seizure Subtype Frequency Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study) |
-7.58; -41.18; -52.54; -24.47 | 0.3478 |
| SECONDARY 50% Responder Rate for All Seizures During Maintenance-LOCF - (for Core Study) |
34.6; 45.7 | 0.1826 |
| SECONDARY 50% Responder Rate for Primary Generalized Seizure Subtype During Maintenance Period - LOCF - (for Core Study) |
39.4; 48.1; 60.9; 41.7 | 0.4653 |
| SECONDARY Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) |
-57.72; -57.40; -100.00; -84.62; -86.81; -86.62 | — |
| SECONDARY Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) |
-77.45; -56.54; -74.21; -63.53; -84.62; -79.49 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events as a Measure of Safety and Tolerability of Perampanel in Subjects With Inadequately Controlled PGTC Seizures - (for Core Study) |
59; 67; 7; 6 | — |
Summary
This study is designed to evaluate the efficacy, safety, and pharmacokinetics (PK) of perampanel on Primary Generalized Tonic Clonic (PGTC) seizure frequency in adolescents and adults maintained on one to two stable antiepileptic drugs (AED).
Eligibility Criteria
Inclusion:
- Clinical diagnosis of PGTC seizures (with or without other subtypes of primary generalized seizures) and experiencing greater than or equal to 3 PGTC seizures during the 8-week period prior to randomization
- Have had a routine electroencephalogram (EEG) prior to or during the Baseline Period with electroencephalographic features consistent with primary generalized epilepsy; other concomitant anomaly should be explained by adequate past medical history
- On a fixed dose of one to a maximum of three concomitant antiepileptic drugs (AEDs) for a minimum of 30 days prior to Baseline; only one inducer AED (i.e., carbamazepine, oxcarbazepine, or phenytoin) out of the maximum of two AEDs will be allowed
- A vagal nerve stimulator (VNS) will be allowed, but it must have been implanted greater than or equal to 5 months prior to Baseline (stimulator parameters cannot be changed for 30 days prior to Baseline and for the duration of the study).
- Have had a computed tomography (CT) or magnetic resonance imaging (MRI) within the last 10 years (for adults) and 5 years (for adolescents) that ruled out a progressive cause of epilepsy
- A ketogenic diet will be allowed as long as the participant has been on this diet for 5 weeks prior to randomization
Exclusion:
- A history of status epilepticus that required hospitalization within 12 months prior to Baseline
- Seizure clusters where individual seizures cannot be counted
- A history of psychogenic seizures
- Concomitant diagnosis of Partial Onset Seizures (POS)
- Progressive neurological disease
- Clinical diagnosis of Lennox-Gastaut syndrome
- If felbamate is used as a concomitant AED, participants must be on felbamate for at least 2 years, with a stable dose for 60 days prior to Baseline. They must not have a history of white blood cell (WBC) count below less than or equal to 2500/microL (2.50 1E+09/L), platelets less than 100,000/microL, liver function tests (LFTs) greater than 3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate.
- Concomitant use of vigabatrin: Participants who took vigabatrin in the past must be discontinued for approximately 5 months prior to Baseline, and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in an automated visual perimetry test
- Concomitant use of barbiturates (except for seizure control indication) within 30 days prior to Baseline
- Use of intermittent rescue benzodiazepines (i.e., one to two doses over a 24-hour period considered one-time rescue) two or more times within the 30 days prior to Baseline
Data sourced from ClinicalTrials.gov (NCT01393743). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.