Abstracts

Rationale: The complex interaction between sleep and epilepsy has long been recognized (Vaughn & D Cruz, Clinical Sleep Disorders, 2010). Seizure activity may be associated with specific phases of the sleep/wake cycle. Seizures and antiepileptic drugs (AEDs) may disrupt sleep patterns, and poor sleep exacerbates seizure activity. Evaluating the effects of an AED on sleep in healthy subjects eliminates the confounding effects of concomitant AED use, co-morbidities, or disease state. Lacosamide (LCM) is an AED approved as adjunctive treatment for partial-onset seizures in adults. This Phase 1, multicenter, interventional, open-label study (NCT01530386) represents the first formal evaluation of LCM on both objective and subjective sleep parameters in healthy subjects.Methods: Healthy subjects with no history of seizures, concomitant AED or other medication use, or primary sleep disorders were enrolled. After screening and an initial overnight polysomnogram (PSG), LCM was initiated at 100mg/d (50mg BID) and increased over 21 days (100mg/d weekly increments) to LCM 300mg/d (mid-range effective dose). To allow subjects to adapt to PSG conditions at Baseline and again after LCM treatment, recordings were performed on 2 consecutive nights with the second night readings used for the analysis. The primary variable was change in Wake After Sleep Onset (WASO) from Baseline to End of Treatment. Secondary variables included Total Sleep Time and Sleep Efficiency; other objective assessments included Time Spent in Sleep Stages, REM Latency, and Sleep Onset Latency. Subject-reported measures of sleep quality and daytime sleepiness were the Pittsburgh Sleep Quality Inventory (PSQI) and the Epworth Sleepiness Scale (ESS). Safety was also assessed. The change from Baseline in WASO was analyzed using the Wilcoxon rank-sum test. For the primary variable, median and range were reported for the observed and change from Baseline results while the median, range and 95% CI were reported for the secondary variables. Results: Twenty-five subjects completed the study. One subject discontinued due to an adverse event prior to receiving LCM and another withdrew consent. The median age was 28 years (range 18 48), and 59.3% were male. Median change in WASO from Baseline to End of Treatment showed a 6-minute reduction in WASO that was not statistically significant (P=0.11; Table 1). Similarly, no changes were observed with respect to Total Sleep Time or Sleep Efficiency (Table 1). Additional objective measures as well as PSQI and ESS results did not reveal an effect of LCM on sleep. Thirteen subjects (48%) had a treatment-emergent adverse event, none of which were severe or led to discontinuation from the study.Conclusions: LCM 300mg/d had no effect on objective sleep parameters in healthy subjects. Results from the objective PSG measurements in this study are consistent with the subject-reported findings that indicate a lack of effect of LCM on sleep quality and daytime sleepiness. In this study with healthy subjects, LCM was generally well tolerated. Funded by UCB Pharma