American Epilepsy Society 63rd Annual Meeting

Poster

Long-Term Safety and Tolerability of Lacosamide for Partial-Onset Seizures

Boston, MA—The purpose of this study, presented as a poster at the annual AES meeting, was to examine the long-term safety of lacosamide (LCM) for partial-onset seizures based on all available data from Phase II-III double-blind and open-label extension trials. William Rosenfeld, MD, of the Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO, and colleagues found that long-term LCM treatment was generally well tolerated in their analysis of 1327 patients exposed to LCM during double-blind or open-label extension trials, with the incidence of treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory and ECG findings similar to those reported with short-term, double-blind use.

Researchers analyzed pooled data for patients treated with LCM in completed double-blind trials and corresponding ongoing open-label extension trials. Data from the double-blind and open-label trials were included for those patients who received LCM in double-blind trials. Data from the transition period at the end of the double-blind trials and from open-label trials were used for those patients who were given placebo in double-blind trials. LCM exposure was relative to the first dose and was based on all available data (double-blind and open-label extension) from visits completed as of an interim analysis cut-off of April 7, 2008. Safety analyses included the following: TEAEs; ECGs; vital signs; body weight; and clinical laboratory data.

1327 patients received at least one dose of LCM, representing 2663 patient-years exposure. The median duration of LCM exposure was 700 days (minimum duration, 1 day; maximum duration, 2437 days). The most common modal dose was 400 mg/day (n=347, 26.1%), with 85.7% of patients (n=1137) having a modal dose of 200-600 mg/day and 8.4% (n=111) having a modal dose of > 600 to ≤ 800 mg/day. At the time of this interim analysis, 526 patients were still enrolled in LCM clinical trials, and 1211 patients (91.3%) had reported at least one TEAE as of the interim analysis cut-off. The most common TEAEs (≥ 10%) were reported as follows: dizziness (45.6%), headache (20.6%), diplopia (18.5%), nausea (15.3%), nasopharyngitis (14.3%), vomiting (14.1%), fatigue (13.8%), coordination abnormal (12.5%), vision blurred (12.0%), tremor (11.5%), somnolence (11.5%), convulsion (11.4%), and confusion (10.4%).

The overall incidence of TEAEs increased with dose, although the increase was not remarkable, and most TEAEs were mild or moderate in intensity. In general, there were no new types of TEAEs thought to be related to the drug that emerged with chronic therapy. Dizziness (4.7%) was the only adverse event for which maximum intensity was reported as “severe” in > 1% of subjects. The most common TEAEs leading to discontinuation (> 1%) were dizziness (5.3%), vomiting (1.6%), nausea (1.5%), diplopia (1.5%), and coordination abnormal (1.5%). Long-term LCM treatment was not associated with any pattern of change in median or mean measurements for hematology, clinical chemistry, vital sign, or body weight. A small increase in mean PR interval of 5-9 ms was noted on ECGs acquired at various times during LCM exposure; however, this did not appear to be clinically relevant, and there were no reports of higher- (second or third) degree heart block.
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Poster

Efficacy and Tolerability of Levetiracetam XR

Boston, MA—Levetiracetam extended-release tablets (Keppra XR) became available in September 2008 for use as an add-on to other antiepileptic treatments for people with partial-onset seizures who are age ≥ 16 years. There are currently few data regarding the drug’s efficacy and tolerability. Researchers retrospectively analyzed data from the electronic medical records of 20 patients with epilepsy treated with Keppra XR with doses ranging from 500-4000 mg per day in the Neurology clinic at the Scott & White Hospital/Texas A&M Health Science Center, Temple. Results, presented as a poster at the AES annual meeting, revealed that good efficacy and tolerability of Keppra XR was seen in the epilepsy population analyzed, and, from the limited retrospective analysis, that Keppra XR was found to be effective as monotherapy.

Keppra XR was used as standard once-a-day dosing. The age range of participants was 15-74 years; 12 (60%) were female and eight (40%) were male. Sixteen (80%) patients had partial and four (20%) had generalized epilepsy. Keppra XR was used as monotherapy in 13 (65%) patients, and was used as adjunctive therapy in seven persons (35%). Thirteen (65%) patients were switched from Keppra IR to Keppra XR because of compliance issues and breakthrough seizures on generic levetiracetam. In six patients, 1:1 switch was made. In two patients, the dose was increased to achieve better control of seizures. Improvement was seen with the decreased dose of Keppra XR as compared to Keppra IR in six patients. There was favorable response to Keppra XR in terms of efficacy in 17 (85%) patients. No major side effects were reported; however, Keppra XR was tapered in three (15%) patients (because of increased frequency of seizures [1 person] and dizziness and mood problems [2 persons]).