Efficacy and Safety of Oral Lacosamide as Adjunctive Therapy in Adults with Partial-Onset Seizures

Ben‐Menachem, Elinor; Biton, Victor; Jatužis, Dalius; Abou‐Khalil, Bassel; Doty, Pamela; Rudd, G. David

doi:10.1111/j.1528-1167.2007.01124.x

Cited by 135 publications

(303 citation statements)

References 6 publications

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“…The rate of seizure freedom observed in other AED trials ranges from approximately 1-20% for treatment versus 0-5% for placebo. 17,18 The proportion of USL255-treated patients who were seizure-free for ≥21 days prior to the last dose of study drug was significantly higher than placebo.…”

Section: Discussionmentioning

confidence: 95%

Once‐daily USL255 as adjunctive treatment of partial‐onset seizures: Randomized phase III study

et al. 2014

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ObjectiveTo evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs.MethodsIn this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated.ResultsAcross the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life.SignificanceThe PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects.

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Section: Discussionmentioning

confidence: 95%

Once‐daily USL255 as adjunctive treatment of partial‐onset seizures: Randomized phase III study

et al. 2014

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“…20 LCM is a functionalized (meaning it passes through the blood-brain barrier) amino acid specifically synthesized as an anticonvulsant drug and has demonstrated antiepileptic activity in several animal seizure models for generalized and complex partial-onset seizures and status epilepticus. 20,21 The clinical efficacy of the oral formulation of LCM as adjunctive therapy for partial-onset seizures has been demonstrated in randomized phase II/III clinical trials 22,23 and long-term follow-up audits. 24 The most frequently reported adverse events in placebocontrolled trials include dizziness, headache, nausea, and diplopia.…”

Section: Lacosamidementioning

confidence: 99%

Medical management of refractory epilepsy—Practical treatment with novel antiepileptic drugs

Ben‐Menachem

2014

Epilepsia

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SUMMARYThe ultimate treatment goal in epilepsy therapy is always freedom from seizures with as few treatment adverse effects as possible. If seizures persist with the first monotherapy, alternative monotherapy with another antiepileptic drug (AED) should be considered. Continuing seizures should lead to a reevaluation of differential diagnosis and adherence. Epilepsy surgery as an alternative therapy may be suitable in selected cases. If the diagnosis of epilepsy is established and epilepsy surgery is not appropriate, AED treatment should be optimized. Evidence for how to proceed is lacking. Concepts such as rational polytherapy have been advocated but remain speculative concerning better efficacy based on the use of AEDs with differing modes of action. A variety of new AEDs including rufinamide, lacosamide, vigabatrin, perampanel, and retigabine have been recently introduced in the United States. They are briefly characterized in this update review.

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“…Prospective studies with larger sample size are, however, needed to explore the role of LCM in polytherapy. Common adverse effects reported in the adult trials and paediatric studies were dizziness, nausea, drowsiness, diplopia, and headaches (Ben-Menachem et al, 2007;Halasz et al, 2009;Chung et al, 2010;Gavatha et al, 2011;Guilhoto et al, 2011;Heyman et al, 2012;Rastogi and Ng, 2012;Kim et al, 2014;Yorns et al, 2014). In our study, similar adverse effects were noted, with dizziness and drowsiness being the most common.…”

Section: Discussionmentioning

confidence: 99%

“…The drug has 100% oral absorption with linear pharmacokinetics, low protein binding (<19%), a 13-hour half-life, renal clearance with limited hepatic metabolism, and a very low potential for drug interactions (Chu-Shore and Thiele, 2010). LCM was found to be effective in adults with focal-onset seizures in three randomized, doubleblind, placebo-controlled studies (Ben-Menachem et al, 2007;Halasz et al, 2009;Chung et al, 2010). These studies have shown that daily administration of 400 to 600 mg of LCM for around three months is associated with a 50% reduction in seizure frequency in around 40% of patients as compared to 18-25% for those taking placebo.…”

Section: Lacosamide As An Adjunctive Therapy For Refractory Focal Epimentioning

confidence: 99%

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single‐centre study

Toupin

Lortie

Major

et al. 2015

Epileptic Disorders

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Aim. Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centre's experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epilepsy. Methods. We retrospectively reviewed the medical records of 22 patients who received lacosamide from November 2009 to April 2014 at the CHU Ste‐Justine, University of Montreal. Treatment responders were defined as children with a ≥50% reduction in seizure frequency compared to baseline, and this was determined three months after the initiation of treatment and at the last follow‐up visit. Results. We included 14 boys and eight girls with a mean age of 12.9 years (SD: 5.2; range: 5.2–20.7 years) at the initiation of treatment. The average length of follow‐up was 11.9 months. Patients had previously received an average of 7.5 antiepileptic drugs. The mean number of concomitant antiepileptic drugs was 2.3. The mean initial and maintenance doses were 2.9 and 8.4 mg/kg/d, respectively. Thirteen (59%) and ten (45%) patients were responders after three months of treatment and at the last follow‐up visit, respectively. One became seizure‐free. Adverse effects were reported in 11 patients and none were severe. Responders and non‐responders were identical with respect to all studied parameters except gender, with the proportion of responders being greater in girls than in boys (75% vs 29%; p=0.035). Conclusion. Our study adds evidence that lacosamide appears to be a safe and effective adjunctive therapy for children with refractory focal epilepsy.

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Efficacy and Safety of Oral Lacosamide as Adjunctive Therapy in Adults with Partial-Onset Seizures

Cited by 135 publications

References 6 publications

Once‐daily USL255 as adjunctive treatment of partial‐onset seizures: Randomized phase III study

Once‐daily USL255 as adjunctive treatment of partial‐onset seizures: Randomized phase III study

Medical management of refractory epilepsy—Practical treatment with novel antiepileptic drugs

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single‐centre study

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