4 mg/day 16 22 14 33
8 mg/day 19 45 12 24
12 mg/day 19 54 9 22
aPatients from Latin American region are excluded because of a significant treatment-by-region interaction due to high placebo response
Table 5. Responder Rate for Combined Studies (Study 1, 2 and 3) Based on the Presence or Absence of Concomitant Enzyme-Inducing AEDs (carbamazepine, oxcarbazepine, phenytoin) a,b Without Enzyme-Inducing AEDs With Enzyme-Inducing AEDs
Placebo
% FYCOMPA
% Placebo
% FYCOMPA
%
2 mg/day 19 26 18 20
4 mg/day 19 35 18 26
8 mg/day 17 45 19 32
12 mg/day 15 54 21 33
aPatients from Latin American region are excluded because of a significant treatment-by-region interaction due to high placebo response
bThe proportion of patients with at least a 50% decrease in seizure frequency
Figure 2 shows the proportion of patients with different percent reductions during the maintenance phase over baseline across all three trials. Patients in whom the seizure frequency increased are shown at left as “worse.” Patients in whom the seizure frequency decreased are shown in the remaining four categories.
Figure 2. Proportion of Patients Exhibiting Different Percent Reductions During the Maintenance Phase Over Baseline Across All Three Trials.
The percentages of patients with a 50% or greater reduction in seizure frequency were 19%, 29%, 35%, 35% for placebo, 4, 8, and 12 mg, respectively.
14.2 Primary Generalized Tonic-Clonic (PGTC) Seizures The efficacy of FYCOMPA as adjunctive therapy in patients 12 years of age and older with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures was established in one multicenter, randomized, double-blind, placebo-controlled study (Study 4), conducted at 78 sites in 16 countries. Eligible patients on a stable dose of 1 to 3 AEDs experiencing at least 3 primary generalized tonic-clonic seizures during the 8-week baseline period were randomized to either FYCOMPA or placebo. Efficacy was analyzed in 162 patients (FYCOMPA N=81, placebo N=81) who received medication and at least one post-treatment seizure assessment. Patients were titrated over 4 weeks up to a dose of 8 mg per day or the highest tolerated dose and treated for an additional 13 weeks on the last dose level achieved at the end of the titration period. The total treatment period was 17 weeks. Study drug was given once per day.
The primary endpoint was the percent change from baseline in primary generalized tonic-clonic seizure frequency per 28 days during the treatment period as compared to the baseline period. The criterion for statistical significance was p<0.05. Table 6 shows the results of this study. A statistically significant decrease in seizure rate was observed with FYCOMPA compared to placebo.
Table 6. Median Percent Reduction from Baseline in Primary Generalized Tonic-Clonic Seizure Frequency in Study 4 Placebo
(N=81) FYCOMPA
8 mg
(N=81)
Percent Reduction During Treatment 38 76a
a P-value compared to placebo: <0.0001. Statistically significant as compared to placebo based on ANCOVA with treatment and pooled country as factors and the ranked baseline seizure frequency per 28 days as a covariate.
Figure 3 shows the proportion of patients with different percent reductions during the maintenance phase over baseline in primary generalized tonic-clonic seizure frequency. Patients in whom the seizure frequency increased are shown at left as “worse.&rd |
