Optimizing Clobazam Treatment in Patients with Lennox-Gastaut Syndrome (LGS) (P2.039)

Objective: To determine the rate of successfully optimized clobazam dosing in patients with LGS stratified by responder status, an analysis of individual patient dosages, and seizure response over the initial 12 months of open-label, flexible treatment with adjunctive clobazam. Background: Clobazam is FDA approved as adjunctive treatment (10-40mg/day) in patients with LGS ≥2years of age. Higher clobazam dosages (up to 80mg/day) were allowed in a phase 3, multicenter, open-label study OV-1004 (NCT01160770) in which patients were dosed to response. Methods: Patients were stratified by partial responder status, determined in a phase 3 lead-in trial (OV-1012; NCT00518713): ≥25[percnt] (25[percnt]-49[percnt]), ≥50[percnt] (50[percnt]-74[percnt]), or ≥75[percnt] (75[percnt]-99[percnt]) reduction in average weekly rate of drop seizures. Patients previously received blinded treatment with placebo or clobazam high [1.0mg/kg; max 40mg/day], medium [0.50mg/kg; max 20mg/day], or low [0.25mg/kg; max 10mg/day] dosages in OV-1012 before transitioning to open-label clobazam (0.5mg/kg for 48 hours). Dosage changes up to 2.0mg/kg (maximum 80mg/day) were determined by the investigator. Dosage optimization was defined as ≥20[percnt] clobazam dosage increase with improved responder status or >50[percnt] additional seizure-frequency reduction (months 3-12). Patients who were previously treated with placebo in OV-1012, seizure-free with clobazam, or had <25[percnt] response were excluded. Results: Seventy-eight of 206 patients with 12-month follow-up data meeting ≥25[percnt], ≥50[percnt], or ≥75[percnt] responder criteria were included. Overall, 75.6[percnt] of patients had a ≥20[percnt] increase in clobazam dosage, with 61.0[percnt] achieving improved seizure control (73.3[percnt], 55.0[percnt], and 58.3[percnt] in the ≥25[percnt], ≥50[percnt], and ≥75[percnt] responder groups, respectively). Conclusions: For patients who responded to double-blind clobazam treatment, ≥20[percnt] dosage increases improved seizure control in ≥60[percnt] of patients during the first year of open-label clobazam treatment. Positive outcome with dosage optimization was most likely in those initially treated with a lower clobazam dosage and in those with lower initial treatment response. Funding: Lundbeck, LLC Disclosure: Dr. Wechsler has received personal compensation for activities with Cyberonics, Eisai, Gerson Lehrman Group Inc., Lundbeck, Sunovion, UCB Pharma, and Upsher-Smith. Dr. Gidal has received personal compensation for activities with Upsher-Smith. Dr. Chung has received personal compensation for activities with UCB Pharma, Eisai, Lundbeck, and Sunovion. Dr. Peng has received personal compensation for activities with Lundbeck. Dr. Isojarvi has received personal compensation fro activities with Lundbeck LLC.