Comparative Cognitive Effects of Lacosamide versus Carbamazepine (P3.191)

Abstract

OBJECTIVE:To evaluate cognitive and EEG effects of lacosamide (LCM) compared to carbamazepine immediate-release (CBZ-IR). BACKGROUND:Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. DESIGN/METHODS:Randomized, double-blind, double-dummy, two-period crossover study (NCT01530022) in healthy controls comparing neuropsychological and EEG effects of LCM (150mg bid) and CBZ-IR (300mg bid, immediate release). Testing was conducted at screening, pre-drug baseline, end of each treatment period (3-week titration; 3-week maintenance), and end of each washout period (4 weeks after treatment). A composite Z-score was derived for the primary outcome variable (computerized cognitive tests and traditional neuropsychological paper/pencil measures, evaluating attention, speed, executive functions, and memory). Other variables included individual subcomponents of the composite score, EEG/EP measures, safety variables, and pharmacokinetic data. RESULTS: 60 healthy adults enrolled (57[percnt] female, mean age 34y [SD 10.5]); 44 completed both treatment periods. The primary analysis included 41 per protocol subjects. Wilcoxon rank sum test revealed worse effects for CBZ-IR compared to LCM for the primary cognitive outcome (0.33 [SD 1.36], p=0.01). Z-score differences compared to non-drug conditions were -0.26 for CBZ-IR and +0.08 for LCM. Secondary analyses of individual variables revealed CBZ-IR was statistically worse than LCM for 25[percnt] (4/16) of the neuropsychological variables and 20[percnt] (1/5) for EEG measures (i.e., P3 latency); none favored CBZ-IR. 22[percnt] of subjects receiving LCM and 49[percnt] receiving CBZ-IR had drug-related adverse events (AEs); 2 LCM and 8 CBZ-IR subjects discontinued due to AEs. CONCLUSIONS: LCM had fewer neuropsychological and EEG effects and fewer AEs and AE-related discontinuations than CBZ-IR in healthy subjects. Significant differences were observed for dual processing, psychomotor speed, perceived drug effects, and P3 latency. LCM exhibits a favorable cognitive profile compared to CBZ-IR. Study Supported by:UCB Pharma

Disclosure: Dr. Loring has received personal compensation for activities with NeuroPace as a consultant. Dr. Meador has received personal compensation for activities on behalf the Epilepsy Study Consortium with Eisai Inc., NeuroPace, Inc., Novartis, Supernus, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals as a consultant. Dr. Meador has rec Dr. Boyd has received personal compensation for activities with CNS Vital Signs as CEO. Dr. Byrnes has received personal compensation for activities with UCB Pharma as an employee. Dr. Dilley has received personal compensation for activities with UCB Pharma. Dr. Borghs has received personal compensation for activities with UCB Pharma as an employee. Dr. De Backer has received personal compensation for activities with UCB Pharma as an employee. Dr. Story has nothing to disclose. Dr. Dedeken has received personal compensation for activities with UCB Pharma as an employee. Dr. Webster has received personal compensation for activities with UCB Pharma as an employee. Dr. Webster holds stock and/or stock options in UCB Pharma.