Abstract Details

Title Carisbamate Treatment of Adult and Pediatric Patients With Lennox-Gastaut Syndrome: A Phase I Pharmacokinetic Dose-Escalation Study

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P9 - Poster Session 9 (11:45 AM-12:45 PM)

Poster/Presentation
Number 9-007

Objective Assess, in a phase 1, open-label study, pharmacokinetics (PK), safety, and tolerability of single-dose (SD) and multiple-dose (MD) adjunctive carisbamate in patients ≥2 years old with Lennox-Gastaut syndrome (LGS).

Background Carisbamate, an investigational antiseizure medication (ASM), is in development for treatment of LGS-associated seizures in adult and pediatric patients.

Design/Methods Patients were enrolled into one of four cohorts: Cohort I (≥18 years), Cohort II (12 to <18 years), Cohort III (6 to <12 years), and Cohort IV (2 to <6 years). Cohorts I-III starting doses were 200, 140, and 60 mg/day, respectively. Cohort IV starting dose and regimen was to be determined from Cohort I-III results. SD phase (Days 1-3): carisbamate oral suspension administered on Day 1 followed by PK sampling for 48 hours. The MD phase (Days 3-87) employed twice-daily divided doses. After Day 17, maximum daily dose allowed was 600 mg/day pediatric equivalent. PK sampling occurred predose and for 12 hours postdose on Day 17. Trough PK sampling occurred on Days 45 and 73.

Results Eighteen patients enrolled (Cohort I, n=8; Cohort II, n=3; Cohort III, n=7; ages 6-52 years); 16 completed the entire study. Cohort IV was withdrawn due to low enrollment. Following SD, carisbamate plasma concentrations reached T_max at 1-2 hours postdose in all three cohorts; increases to mean C_max, AUC_0-last, and AUC_0-infwere linear and dose-proportional. MD steady-state PK parameters on Day 17 increased in a linear and dose-proportional manner. The most frequently reported treatment-emergent adverse events (TEAEs) were nervous system-related; most were mild (n=6, 33.3%) or moderate (n=5, 27.8%).

Conclusions Carisbamate exhibited linear, dose-proportional PK after SD and MD in pediatric and adult patients with LGS and was generally safe and well-tolerated. PopulationPK modeling showed that adult dosing regimens were appropriate for patients ≥12 years of age whereas dosing for patients ages 4 to <12 should be weight-based.

Authors/Disclosures
Vijay Vashi (SK LIFE SCIENCE, INC) PRESENTER	Dr. Vashi has received personal compensation for serving as an employee of SK LIFE SCIENCE, INC.
David G. Vossler, MD, FAAN (David G. Vossler MD FAAN FAES FACNS)	Dr. Vossler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Longboard Pharmaceuticals. Dr. Vossler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Xenon Pharmaceuticals. Dr. Vossler has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for SK Life Science. The institution of Dr. Vossler has received research support from Xenon Pharmaceuticals. The institution of Dr. Vossler has received research support from Longboard Pharmaceuticals. Dr. Vossler has received publishing royalties from a publication relating to health care.

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