TRILEPTAL Rx

Trileptal Monotherapy Trials 

• The efficacy of Trileptal as monotherapy was also evaluated in a randomized, controlled, rater-blind, multicenter study in pediatric patients. Results showed that there was not a statistically significant difference between low and high dose Trileptal treatment groups.

• In a placebo-controlled trial, Trileptal was evaluated in 102 patients 11 to 62 years of age with refractory partial-onset seizures who had completed an inpatient evaluation for epilepsy surgery. Eligible patients were required to have 2 to 10 partial-onset seizures within 48 hours prior to randomization. Patients were randomly assigned to receive placebo or Trileptal 1500 mg/day on Day 1 and 2400 mg/day thereafter for an additional 9 days, or until exit criteria occurred. Results showed that there was a statistically significant difference in favor of Trileptal.

• In a second placebo-controlled trial, Trileptal was evaluated in 67 patients with newly-diagnosed and recent-onset partial seizures. Patients were randomly assigned to placebo or Trileptal initiated at 300 mg twice a day and titrated to 1200 mg/day in 6 days, then maintenance treatment for 84 days. Results showed that there was a statistically significant difference in favor of Trileptal (P =.046).

• In a third trial, Trileptal monotherapy at 2400 mg/day was substituted for carbamazepine in 143 patients 12 to 65 years of age whose partial-onset seizures were inadequately controlled on carbamazepine (CBZ) monotherapy at a stable dose of 800 to 1600 mg/day, and maintained this Trileptal dose for 56 days (baseline phase). The difference between the curves was statistically significant in favor of the Trileptal 2400 mg/day group (P =.0001).  

• A fourth monotherapy substitution trial was conducted in 87 patients 11 to 66 years of age whose seizures were inadequately controlled on 1 or 2 AEDs. Patients were randomly assigned to either Trileptal 2400 mg/day or 300 mg/day and their standard AED regimen(s) were eliminated over the first 6 weeks of double-blind therapy. Double-blind treatment continued for another 84 days (total double-blind treatment of 126 days) or until 1 of the 4 exit criteria described for the previous study occurred. The results were statistically significant in favor of the Trileptal 2400 mg/day group (14/34; 41.2%) compared to the Trileptal 300 mg/day group (42/45; 93.3%) (P <.0001). The time to meeting one of the exit criteria was also statistically significant in favor of the Trileptal 2400 mg/day group (P =.0001).

• Another monotherapy trial was conducted in 92 pediatric patients 1 month to 16 years of age with inadequately-controlled or new-onset partial seizures. Patients were hospitalized and randomized to either Trileptal 10 mg/kg/day or were titrated up to 40 to 60 mg/kg/day within 3 days while withdrawing the previous AED on the second day of Trileptal. The primary measure of effectiveness was a between-group comparison of the time to meet exit criteria in which the difference between the curves was not statistically significant (P =.904). The majority of patients from both dose groups completed the 5-day study without exiting.

Trileptal Adjunctive Therapy Trials 

• 2 multicenter, randomized, double-blind, placebo-controlled trials evaluated the efficacy of Trileptal as adjunctive therapy for partial-onset seizures in: 692 patients 15 to 66 years of age, and 264 pediatric patients 3 to 17 years of age. Patients were on 1 to 3 concomitant AEDs. Patients were randomly assigned to receive placebo or to a specific dose of Trileptal in addition to other AEDs.

• In the adult trial, patients received fixed doses of 600, 1200 or 2400 mg/day. In the pediatric trial, patients received maintenance doses in the range of 30 to 46 mg/kg/day, depending on baseline weight. The primary measure of effectiveness in both trials was a between-group comparison of the percentage change in partial-onset seizure frequency in the double-blind treatment phase relative to baseline phase. This comparison was statistically significant in favor of Trileptal at all doses tested in both trials (P =.0001 for all doses for both trials). 

• The third adjunctive therapy trial enrolled 128 pediatric patients (1 month to <4 years of age) with inadequately-controlled partial-onset seizures on 1 to 2 concomitant AEDs. Patients who experienced at least 2 study-specific seizures (i.e., electrographic partial-onset seizures with a behavioral correlate) during the 72-hour baseline period were randomly assigned to either Trileptal 10 mg/kg/day or were titrated up to 60 mg/kg/day within 26 days. Patients were maintained on their randomized target dose for 9 days and seizures were recorded through continuous video-EEG monitoring during the last 72 hours of the maintenance period. The primary measure of effectiveness in this trial was a between-group comparison of the change in seizure frequency per 24 hours compared to the seizure frequency at baseline. For the entire group of patients enrolled, this comparison was statistically significant in favor of Trileptal 60 mg/kg/day. In this study, there was no evidence that Trileptal was effective in patients below the age of 2 years.