No Metabolic Effects with Novel Antiepileptic Drug
Honolulu—Treatment-related metabolic effects are a concern for adults who depend on long-term drug therapy to prevent seizures. A recent pooled analysis of two phase 3 trials comparing eslicarbazepine acetate, a novel antiepileptic drug (AED), with placebo found that the novel agent had no clinically meaningful effect on metabolic parameters such as weight, glucose levels, lipid fractions, and liver enzymes. Data from this retrospective analysis were presented in a poster session at the AAN meeting. The poster was titled An Evaluation of the Effect of Eslicarbazepine Acetate on Weight, Glucose, and Lipids: An Integrated Analysis of Two Double-Blind Phase III Clinical Studies. The authors describe eslicarbazepine as a “voltage-gated sodium channel blocker” under development to prevent partial-onset seizures in adults.
In 2 double-blind, randomized phase 3 studies, the safety and efficacy of various doses of eslicarbazepine were compared with placebo in patients taking 1 to 3 AEDs. Cumulatively, the safety population (patients who received ≥1 dose) comprised 797 patients randomized to placebo (n=202) or eslicarbazepine, administered daily in doses of 400 mg (n=196), 800 mg (n=199), or 1200 mg (n=200). Investigators for the pooled analysis evaluated the mean change in several metabolic parameters from baseline to 14 weeks, which is when both trials were unblinded. They also sought to establish the proportion of patients in each cohort who experienced potentially clinically significant changes in weight or other metabolic measures during the trial and quantified treatment-emergent adverse events (TEAEs) per cohort.
In analyzing mean change from baseline in aspartate transaminase (AST) and alanine transaminase (ALT) fractions, glucose levels, and lipid parameters, researchers censored data for certain participants. This left 183 patients in the placebo cohort; in the eslicarbazepine cohort, data were considered for 144 patients in the 1200-mg arm, 166 in the 800-mg arm, and 178 (glucose analysis)/179 (AST, ALT, and lipid parameters) in the 400-mg arm. The analysis of weight change included data for 2 to 3 more patients per cohort, except in the eslicarbazepine 1200-mg group, which had 1 fewer patient. In assessing potentially clinically significant changes in these measures from baseline, the authors found patients receiving eslicarbazepine were more likely to experience a weight increase ≥7% compared with patients taking placebo. This extent of weight gain was more prevalent among patients assigned the lowest eslicarbazepine dose and least prevalent among those receiving the 1200-mg daily dose.
Patients randomized to eslicarbazepine were also more likely than those taking placebo to have an increase >300 mg/dL in total cholesterol level (3.7% vs 2.0%, respectively) and an increase >160 mg/dL in low-density lipoprotein cholesterol (LDL-C) level. Comparisons between each eslicarbazepine dosing arm with placebo showed only minor differences in the proportions of patients with an increase >160 mg/dL in their LDL-C level, ranging from 0.5% to 4.3%. The poster authors said they were unable to detect a “consistent pattern of potentially clinically significant values” in any treatment group regarding any metabolic parameter examined. Nor did they observe any clinically meaningful change in these parameters from baseline associated with eslicarbazepine use. Research for this study was sponsored by BIALPortela & CA, SA in Portugal.
