Study results show a novel formulation of oxcarbazepine may provide long-term seizure reduction in patients with refractory epilepsy, while a separate trial produced promising results for long-term lacosamide treatment in elderly patients with partial-onset seizures.
In “Long-Term, Open-Label Safety and Tolerability Study of Once-Daily Extended-Release Oxcarbazepine (SPN-804) as Adjunctive Therapy in Patients with Refractory Partial Seizures,” Johnson and colleagues assessed “the long-term safety and tolerability of SPN-804, a novel once-daily formulation of oxcarbazepine, in refractory partial epilepsy” during a randomized, double-blind, placebo-controlled trial of adults with refractory partial epilepsy “despite up to 3 concomitant antiepilepsy drugs.” Patients received SPN-804 1200 mg/d over two weeks, followed by dose adjustments (600-2400 mg/d) and concomitant AEDs, if needed.
Primary endpoints were long-term safety and tolerability; secondary endpoint was “effect on percent change in partial seizure frequency/28 days (PCHT) vs double-blind results.” More than two-thirds of patients (248 of 366) completed the study, with 214 (58.5%) receiving treatment with SPN-804 during the open-label extension phase. More than 80% (179) of these patients completed treatment. Average duration of treatment was 356.4 days.
The authors reported that “Median PCHT reduction was -58.95 and -26.25 relative to the end of baseline and maintenance periods of the double-blind study, respectively.” Nearly one-third (32.2%) of patients experienced treatment-related adverse events (AEs), with 11 patients (5.1%) discontinuing treatment due to AEs. The most frequently reported AEs were dizziness, headache, diplopia, nausea, vomiting, and somnolence, with AEs rates decreasing during the open-label extension phase, “possibly because 64.1% of patients were already exposed to SPN-804 in the double-blind study.” Although most AEs were mild to moderate, 15 patients did experience a serious AE.
The authors concluded that this one-year follow-up study “showed that adjunctive SPN-804 was well tolerated and further reduced seizure frequency beyond that observed during the double-blind study. Once-daily SPN-804 may provide long-term improvement in tolerability, adherence, and seizure reduction in patients with refractory epilepsy.”
In another study looking at pharmacologic treatment options for partial seizures, “Evaluation of Long-Term Treatment with Lacosamide for Partial-Onset Seizures in the Elderly,” Rosenfeld and colleagues evaluated the long-term efficacy and tolerability of lacosamide in patients age 65 years and older. The long-term efficacy and safety of adjunctive lacosamide has been studied in several open-label extension (OLE) trials of elderly patients. The authors pooled data from three such trials (SP615[NCT00522275], SP756[NCT00552305], SP774[NCT00515619]) in adults with partial-onset seizures who were treated with adjunctive lacosamide.
Out of a cohort of 1,054 patients treated with lacosamide, 13 were over age 65 at baseline and 33 were over age 65 at completion. The authors report that “Mean and maximum lacosamide treatment durations were 1563.2 and 2790.0 days; median modal dose was 400mg/day.” More than 90% of elderly patients continued with the trial after one year, 75% after three years, and 42% after five, with the most common reasons for discontinuing treatment being adverse events (AEs), lack of efficacy, and withdrawal of consent. Common AEs included dizziness, fall, cognitive disorder, tremor, headache, depression, urinary tract infection, diplopia, balance disorder, or pain in extremity.
Analysis of data showed that median percent reduction in seizure frequency from baseline for patients who complete one, three, and five years of treatment was was 62.5%, 58.2% and 66.6%, respectively. Rates of 50%+ responders were 63.3%, 68.0% and 64.3%. Based on these results, the authors concluded that long-term lacosamide treatment was generally well tolerated in this small population of elderly patients, and “was associated with a reduction in seizure frequency and maintenance of efficacy similar to the overall OLE patient pool.”