TRIAL PATIENTS HAD HISTORY OF MULTIPLE SEIZURE TYPES, UNCONTROLLED ON 1-3 AEDs1-3

Trial design1,3

BANZEL trial patients had a history of multiple seizure types and were uncontrolled on 1-3 AEDs. The prospective baseline was assessed at 28 days (n=139). At randomization 74 patients took BANZEL (who were on 1-3 AEDs) and 64 patients took placebo (who also was on 1-3 AEDs). Both of these patient groups were titrated for 14 days then placed on a maintenance dose for 70 days. After 12 weeks, the open-label extension portion of the trial began with 124 BANZEL patients. The open-label extension period lasted 3 years beginning with a 2-week double-blind conversion phase. BANZEL trial patients had a history of multiple seizure types and were uncontrolled on 1-3 AEDs. The prospective baseline was assessed at 28 days (n=139). At randomization 74 patients took BANZEL (who were on 1-3 AEDs) and 64 patients took placebo (who also was on 1-3 AEDs). Both of these patient groups were titrated for 14 days then placed on a maintenance dose for 70 days. After 12 weeks, the open-label extension portion of the trial began with 124 BANZEL patients. The open-label extension period lasted 3 years beginning with a 2-week double-blind conversion phase.

*Approximately 3 years beginning with a 2-week, double-blind conversion phase.

  • A 12-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group trial to assess the effectiveness of BANZEL (rufinamide) to reduce inadequately controlled seizures associated with LGS in patients (N=138, intent to treat) being treated with 1-3 concomitant stable-dose AEDs1-3
  • The primary efficacy variables were the percent change in total seizure frequency per 28 days, the percent change in tonic-atonic (drop attacks) seizure frequency per 28 days, and the seizure severity rating from the parent/guardian global evaluation of the patient's condition1
  • All 3 primary endpoints met the prespecified statistical criteria for effectiveness1

BANZEL® trial population: key inclusion criteria1,3

Image of ≥90 in bold large lettering. This shows an aspect of the BANZEL trial population key inclusion criteria which included those patients who experienced ≥90 seizures in the month prior to baseline.

seizures in month prior to baseline

graphical interpretation of multiple seizure types. The BANZEL trial population included those patients with a history of multiple seizure types. This was a key inclusion criteria for the study.

History of multiple seizure types

icon of a person. The BANZEL trial population included those patients with a history of tonic-atonic and atypical absence seizures. This was a key inclusion criteria for the study.

History of tonic-atonic and atypical absence seizures

icons of a pill and tablet which represent a key inclusion criteria of the BANZEL clinical trial which included those patients who were inadequately controlled with 1-3 AEDs.

Inadequately controlled with 1-3 AEDs

Presents a partial list of criteria; there were additional inclusion and exclusion criteria in the pivotal trial.

Median number of total seizures in the 2 treatment groups during the 28-day baseline phase1:

BANZEL® 290 (n=74)
Placebo 205 (n=64)

BANZEL® pivotal trial entry criteria

Patients in the BANZEL trial were subject to the following entry criteria

INCLUSION
EXCLUSION
Age 4-30 years at randomization
On ketogenic diet or have received ACTH within 6 months prior to baseline
Minimum of 90 seizures in the month prior to baseline period
Pregnant, not using adequate contraception, or nursing mothers
History of multiple seizure types, which had to include tonic-atonic and atypical absence
Had a treatable cause of their seizures (active infection, neoplasm, metabolic disturbance)
Slow spike-and-wave EEG pattern within 6 months of study entry
Had a history of generalized tonic-clonic status epilepticus within 30 days before baseline
Minimum weight of 18 kg (40 lb) at randomization
Concomitant use of felbamate or received felbamate within 2 months prior to baseline
INCLUSION
Age 4-30 years at randomization
Minimum of 90 seizures in the month prior to baseline period
History of multiple seizure types, which had to include tonic-atonic and atypical absence
Slow spike-and-wave EEG pattern within 6 months of study entry
Minimum weight of 18 kg (40 lb) at randomization
EXCLUSION
On ketogenic diet or have received ACTH within 6 months prior to baseline
Pregnant, not using adequate contraception, or nursing mothers
Had a treatable cause of their seizures (active infection, neoplasm, metabolic disturbance)
Had a history of generalized tonic-clonic status epilepticus within 30 days before baseline
Concomitant use of felbamate or received felbamate within 2 months prior to baseline

This is not the complete list of inclusion/exclusion criteria.

  • Baseline characteristics of BANZEL study participants were similar between study groups (BANZEL vs placebo):
    • Gender (62.2% male vs 62.5% male), median age (13 years vs 10.5 years), median duration of LGS (8 years vs 8 years), and median weight (36 kg vs 34 kg)

Multiple seizure types observed at baseline

≥50% of BANZEL patients presented with tonic-atonic, atypical absence, tonic, atonic, myoclonic, and/or tonic-clonic seizures

Percentage of trial patients with specific seizures at baseline1,3

Shows the percentage of BANZEL trial patient with specific seizures at baseline. There were 99% of BANZEL patients that experienced tonic –atonic seizures compared to 94% of placebo patients;  80% of BANZEL patients vs 86% placebo for atypical absence; 70% of BANZEL patients vs 67% experienced tonic seizures;  61% of BANZEL patients vs 52% of placebo patients experienced atonic seizures;  50% of BANZEL patients versus 48% of placebo patients experienced myoclonic seizures; 50% of BANZEL patients vs 42% of placebo patients experienced tonic-clonic seizures; 16% of BANZEL patients experienced unclassified siezures compared to 20% of placebo patients; 15% of BANZEL patients experienced partial seizures compared to 14% of placebo patients; 11% of BANZEL patients experienced absence seizures compared to 8% of placebo patients;  and 9% of BANZEL patients experienced clonic seizures compared to 2% of placebo patients. Shows the percentage of BANZEL trial patient with specific seizures at baseline. There were 99% of BANZEL patients that experienced tonic –atonic seizures compared to 94% of placebo patients;  80% of BANZEL patients vs 86% placebo for atypical absence; 70% of BANZEL patients vs 67% experienced tonic seizures;  61% of BANZEL patients vs 52% of placebo patients experienced atonic seizures;  50% of BANZEL patients versus 48% of placebo patients experienced myoclonic seizures; 50% of BANZEL patients vs 42% of placebo patients experienced tonic-clonic seizures; 16% of BANZEL patients experienced unclassified siezures compared to 20% of placebo patients; 15% of BANZEL patients experienced partial seizures compared to 14% of placebo patients; 11% of BANZEL patients experienced absence seizures compared to 8% of placebo patients;  and 9% of BANZEL patients experienced clonic seizures compared to 2% of placebo patients.

BANZEL® was studied as adjunctive treatment with a range of AEDs

Concomitant AEDs in the BANZEL® clinical trial

Shows that BANZEL was studied as an adjunctive treatment with a range of AEDs. This chart shows a list of concomitant AEDs in the BANZEL clinical trial. Concomitant AEDs were used by at least 10% of patients included: valproate, lamotrigine, topiramate, clonazepam, carbamazepine, clobazam, phenytoin and phenobarbital. Percentage of concomitant use was as follows: Valproate was used by 60% of the BANZEL patients compared to 55% of those on placebo. Lamotrigine was used by 41% of BANZEL patients compared to 30% of those on placebo. Topiramate was used by 27% of BANZEL and placebo patients. Clonazepam was used by 19% of BANZEL patients and 11% of placebo patients. Carbamazepine was used by 16% of BANZEL patients compared to 19% of placebo patients. lobazam was used by 14% of BANZEL patients compared to 13% of placebo patients. Phenytoin was used by 14% of BANZEL patients compared to 19% of placebo patients. Phenobarbital was used by 8% of BANZEL patients compared to 14% of placebo patients. Shows that BANZEL was studied as an adjunctive treatment with a range of AEDs. This chart shows a list of concomitant AEDs in the BANZEL clinical trial. Concomitant AEDs were used by at least 10% of patients included: valproate, lamotrigine, topiramate, clonazepam, carbamazepine, clobazam, phenytoin and phenobarbital. Percentage of concomitant use was as follows: Valproate was used by 60% of the BANZEL patients compared to 55% of those on placebo. Lamotrigine was used by 41% of BANZEL patients compared to 30% of those on placebo. Topiramate was used by 27% of BANZEL and placebo patients. Clonazepam was used by 19% of BANZEL patients and 11% of placebo patients. Carbamazepine was used by 16% of BANZEL patients compared to 19% of placebo patients. lobazam was used by 14% of BANZEL patients compared to 13% of placebo patients. Phenytoin was used by 14% of BANZEL patients compared to 19% of placebo patients. Phenobarbital was used by 8% of BANZEL patients compared to 14% of placebo patients.
Safety and effectiveness have been established in pediatric patients 1 to 17 years of age. The effectiveness of BANZEL in pediatric patients 4 years of age and older was based upon an adequate and well-controlled trial of BANZEL that included both adults and pediatric patients, 4 years of age and older, with Lennox-Gastaut syndrome. The effectiveness in patients 1 to less than 4 years was based upon a bridging pharmacokinetic and safety study. The pharmacokinetics of rufinamide in the pediatric patients ages 1 to less than 4 years of age is similar to children older than 4 years of age and adults.
  • References: 1. Glauser et al. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology. 2008;70(21):1950-1958. 2. BANZEL® (rufinamide) prescribing information, Eisai Inc. 3. Data on file, Eisai Inc.