Long‐term safety and efficacy in patients with uncontrolled partial‐onset seizures treated with adjunctive lacosamide: Results from a phase III open‐label extension trial

Abstract

and xUCB Pharma, Raleigh, North Carolina, U.S.A. SUMMARYPurpose: To evaluate the long-term (up to 5 years exposure) safety and efficacy of lacosamide as adjunctive therapy in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs) in open-label extension trial SP756 (NCT00522275). Methods: Patients who completed the double-blind trial SP754 (NCT00136019) were eligible to participate in this open-label extension trial (SP756). At the conclusion of trial SP754, patients had transitioned to lacosamide 200 mg/day. Subsequent dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant AEDs were allowed to optimize tolerability and seizure reduction. Treatment-emergent adverse events (TEAEs), vital signs, body weight, clinical laboratory data, electrocardiography studies, and seizure frequency were evaluated. Key Findings: A total of 308 patients received open-label lacosamide and 138 patients (44.8%) completed the longterm trial. The median modal dose (defined as the daily lacosamide dose a patient received for the longest duration during the treatment period) was 500 mg/day. The percentages of patients with lacosamide exposure >1, >2, >3, or >4 years were 75%, 63%, 54%, and 29%, respectively. Primary reasons for discontinuation were lack of efficacy (26%) and adverse events (11%). Common TEAEs ( ‡15%) were dizziness, headache, contusion, nausea, convulsion, nasopharyngitis, fall, vomiting, and diplopia. TEAEs that led to discontinuation in ‡1.0% of patients were dizziness (1.6%) and convulsion (1.0%). The median percent reductions from baseline of trial SP754 in 28-day seizure frequency were 53.4%, 55.2%, 58.1%, and 62.5%, respectively, for 1-, 2-, 3-, and 4-year completers. The ‡50% responder rates were 52.8%, 56.5%, 58.7%, and 62.5% for 1-, 2-, 3-, and 4-year completers, respectively. Seven of eight patients on lacosamide monotherapy for ‡12 months were deemed 50% responders. Of patients exposed to lacosamide ‡2 years, 3.1% remained seizure-free for a period ‡2 years. Significance: Long-term (up to 5 years) lacosamide treatment was generally well tolerated. The safety profile of lacosamide observed in this trial is consistent with that established in previous double-blind, placebo-controlled trials. Although the open-label trial design limits the analysis of efficacy, long-term reduction in seizure frequency and maintenance of efficacy was observed.

Long‐term efficacy and safety of adjunctive extended‐release oxcarbazepine (Oxtellar XR ® ) in adults with partial‐onset seizures

“…Levetiracetam was associated with the highest retention rates, with 60–75% of patients continuing treatment at 1 year. Most recently, results from open‐label extensions to Phase 3 double‐blind, placebo‐controlled trials have been reported for the ‘third‐generation’ AEDs lacosamide (LCM) 15 and perampanel (PER) 16. Outcomes were consistent with those reported in the meta‐analysis of second‐generation AEDs.…”

Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy

“…The approval of LCM as adjunctive therapy in focal epilepsy was based on the results of three pivotal trials,13, 14, 15 all followed by open‐label extensions 16, 17, 18. In the pivotal trials, patients with highly refractory disease received LCM in a fixed titration scheme added to a variety of AEDs—up to 82% had a SCB in their treatment regimen 9, 19.…”

Health Technology Assessment of Lacosamide as Adjunctive Therapy for Partial-Onset Epileptic Seizures

“…Few studies have focused on adjunctive therapy with lacosamide for partial-onset seizures in adult patients: the researcher identified 32 citations, but only nine studies were included in the review: three randomized controlled trials published in peer-reviewed journals14-16, three open-label extension studies published as abstracts (Ben-Menachem et al, 2009;Rosenfeld et al, 2009;Faught et al, 2010;Husain et al, 2010), one economic evaluation published in a peer-reviewed journal (Bolin et al, 2010), and two economic evaluations published as abstracts (one of which also included a budget impact analysis) Soini et al, 2009). Studies were excluded because of one or more of the following reasons: disease other than refractory epilepsy; study not involving lacosamide; study of intravenous lacosamide; study of pharmacodynamic and/or pharmacokinetic profile of lacosamide; literature review rather than original study; case study.…”

“…Adverse events were reported to be of mild or moderate intensity. Three open-label extension studies of the pivotal trials explored the long-term safety, tolerability and efficacy of lacosamide (see Table 1) (Ben-Menachem et al, 2009;Rosenfeld et al, 2009;Faught et al, 2010;Husain et al, 2010). Long-term treatment with lacosamide produced a sustained efficacy in and was generally well tolerated by patients suffering from partial-onset seizures.…”