Annals of Long Term Care

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.

One thousand three hundred twenty-seven 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 (dose used for the longest period of time) 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.

Poster

Efficacy and Tolerability of Levetiracetam

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 and older. There are currently few data regarding the drug’s efficacy and tolerability.