[Show abstract][Hide abstract] ABSTRACT: Efficacy and safety of adjunctive rufinamide (3,200 mg/day) was assessed in adolescents and adults with inadequately controlled partial-onset seizures receiving maintenance therapy with up to three antiepileptic drugs (AEDs).
This randomized, double-blind, placebo-controlled, parallel-group, multicenter study comprised a 56-day baseline phase (BP), 12-day titration phase, and 84-day maintenance phase (MP). The primary efficacy variable was percentage change in total partial seizure frequency per 28 days (MP vs. BP). Secondary efficacy outcome measures included ≥50% responder rate and reduction in mean total partial seizure frequency during the MP. Safety and tolerability evaluation included adverse events (AEs), physical and neurologic examinations, and laboratory values. Pharmacokinetic and pharmacodynamic assessments were conducted.
Three hundred fifty-seven patients were randomized: 176 to rufinamide and 181 to placebo. Patients had a median of 13.3 seizures per 28 days during BP; 86% were receiving ≥2 AEDs. For the intent-to-treat population, the median percentage reduction in total partial seizure frequency per 28 days was 23.25 for rufinamide versus 9.80 for placebo (p = 0.007). Rufinamide-treated patients were more than twice as likely to have had a ≥50% reduction in partial seizure frequency (32.5% vs. 14.3%; p < 0.001) and had a greater reduction in median total partial seizure rate per 28 days during the MP (13.2 vs. 5.2; p < 0.001). Treatment-emergent AEs occurring at ≥5% higher incidence in the rufinamide group compared with placebo were dizziness, fatigue, nausea, somnolence, and diplopia.
Adjunctive treatment with rufinamide reduced total partial seizures in refractory patients. AEs reported were consistent with the known tolerability profile of rufinamide.
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy, safety, tolerability, and pharmacokinetics of adjunctive rufinamide in adults and adolescents with inadequately controlled partial seizures receiving treatment with one to three concomitant antiepileptic drugs (AEDs).
A 24-week multicenter Phase II clinical study was conducted (n=647), comprising a 12-week prospective baseline phase and a 12-week randomized double-blind, parallel-group, five-arm (placebo and rufinamide 200, 400, 800, and 1600mg/day) treatment phase.
The linear trend of dose response for seizure frequency per 28 days in the double-blind treatment phase - the primary efficacy outcome measure - was statistically significant in favor of rufinamide (estimated slope=-0.049, P=0.003; minimally efficacious dose, 400mg/day). Response rates, defined as a >or=50% reduction in seizure frequency per 28 days, also revealed a significant linear trend of dose response (P=0.0019, logistic regression analysis). Adverse events were comparable between placebo and all rufinamide groups except the 1600mg/day group; no safety signals were observed.
These results suggest that in the dose range of 400-1600mg/day, add-on rufinamide therapy may benefit patients with inadequately controlled partial seizures and is generally well tolerated. These data also suggest that higher doses may confer additional efficacy without adversely affecting safety and tolerability.
No preview · Article · Feb 2010 · Epilepsy research
[Show abstract][Hide abstract] ABSTRACT: Rufinamide is a novel antiepileptic agent recently approved in the United States for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. To help inform clinical decision making, the authors analyzed safety and tolerability data from the entire pediatric population in the rufinamide epilepsy clinical development program. The analysis population comprised 212 rufinamide-treated (age range 3-16 years) and 197 placebo patients (age range 4-17 years) in the double-blind studies, and 391 patients receiving rufinamide in the double-blind and/or open-label extensions. The most common adverse effects observed in rufinamide-treated patients in the double-blind studies were somnolence, vomiting, and headache. Changes in laboratory values, vital signs, and weight were generally clinically insignificant. This pooled analysis of data from pediatric patients in clinical studies of rufinamide for the treatment of seizures, mainly as adjunctive therapy, suggests a favorable safety and tolerability profile in this patient population.
No preview · Article · Dec 2009 · Journal of child neurology
[Show abstract][Hide abstract] ABSTRACT: To evaluate efficacy and safety of adjunctive treatment with rufinamide 1600 mg twice daily in subjects aged > or = 16 years with refractory partial seizures.
This double-blind, placebo-controlled, randomized, parallel-group, multicenter trial included an 8-week baseline phase and a 13-week double-blind phase. Treatment was initiated with rufinamide 400 mg twice daily or placebo; rufinamide was titrated to 1600 mg twice daily. Percentage change in partial seizure frequency was the primary outcome measure. Secondary outcome measures included total partial seizure frequency and the percentage of subjects experiencing a >/=50% reduction in partial seizure frequency.
Three hundred thirteen subjects were randomized; 156 subjects received rufinamide and 157 received placebo. Rufinamide-treated subjects experienced a 20.4% median reduction in partial seizure frequency relative to baseline, while placebo-treated subjects had an increase of 1.6% (p = 0.02). Exclusion of subjects taking carbamazepine in a post hoc analysis resulted in a reduction of 29.2% versus 0.7% in the placebo group (p = 0.05), whereas the treatment difference in subjects taking carbamazepine was not significant. Of rufinamide-treated subjects, 28.2% experienced a > or = 50% decrease in partial seizure frequency versus 18.6% of placebo-treated subjects (p = 0.04). The most common adverse events associated with rufinamide treatment were dizziness, nausea, diplopia, and ataxia; they occurred primarily during the titration phase.
Adjunctive therapy with rufinamide 3200 mg/day compared with matching placebo demonstrated efficacy and was generally well tolerated in adults with partial seizures. Further study of this agent in adults with partial seizures taking a range of baseline AEDs is warranted.