Abstracts

Rationale: There is a need for additional treatment options for acute seizures. EP0087 (NCT03021018) was a phase 2, open-label, randomized, parallel-group, active-controlled proof of concept US trial to assess the efficacy and safety of intravenous (IV) brivaracetam (BRV) vs IV lorazepam (LZP) in patients with epilepsy undergoing evaluation in an Epilepsy Monitoring Unit (EMU) who experience seizures requiring prompt treatment. Methods: Patients aged 18 to 70 years admitted to EMU for seizure characterization or noninvasive presurgical evaluation were randomized 1:1:1 to single-dose bolus IV LZP (dose as per Investigator’s usual practice), IV BRV 100 mg, or IV BRV 200 mg. Trial medication was administered when the Investigator determined by clinical observation and electroencephalogram (EEG) that a seizure requiring intervention had started (LZP: injected at a rate of ≤ 2.0 mg/min, BRV 100 mg: 10 mL administered IV over approximately 2 minutes, BRV 200 mg: 20 mL administered IV over approximately 4 minutes). Treatment period was from trial medication administration up to 12 hours or until next seizure or until rescue medication administration. Safety follow-up period was from the end of the treatment period to 24 hours. Primary efficacy outcome was time to next seizure (per clinical observation with EEG confirmation) or rescue medication. Secondary outcomes were time to next seizure (per clinical observation only) or rescue medication, and proportion of patients seizure free at 12 hours and proportion receiving rescue medication at 6, 8, and 12 hours after the end of trial medication administration. Safety outcomes included treatment-emergent adverse events (TEAEs), medication-related TEAEs, and serious TEAEs. Descriptive results are reported. Results: Forty-five patients were randomized and received at least one dose of trial medication for a qualifying seizure; patients were similar across treatment groups (Table). Eleven of the 45 patients had a seizure within 12 hours (LZP=5, BRV 100 mg=3, BRV 200 mg=3), suggesting similar efficacy across treatments as evidenced by Kaplan-Meier analysis (Figure). Most patients were seizure free over the 12 hours after receiving trial medication: LZP (9/15 patients; 60.0%), BRV 100 mg (12/15; 80.0%), BRV 200 mg (12/15; 80.0%). Rescue medication use at 6, 8, and 12 hours after trial medication administration was numerically higher for LZP (20.0%, 26.7%, 40.0%) vs BRV 100 mg (0%, 6.7%, 6.7%) and vs BRV 200 mg (6.7%, 13.3%, 13.3%). TEAEs were reported by 31.3%, 40.0%, and 20.0% of LZP, BRV 100 mg, and BRV 200 mg patients, respectively, and serious TEAEs by one LZP patient (6.3%) only. Medication-related TEAEs were reported by 25.0%, 20.0%, and 6.7% of LZP, BRV 100 mg, and BRV 200 mg patients, respectively. The most common TEAEs (≥ 10% of patients in any group) were dizziness (20.0% BRV 100 mg, 6.7% BRV 200 mg, 0% LZP), nausea (13.3% each for BRV 100 mg and BRV 200 mg, 0% LZP), headache (13.3% BRV 100 mg, 6.3% LZP, 0% BRV 200 mg), sedation (12.5% LZP, 6.7% BRV 200 mg, 0% BRV 100 mg), and somnolence (12.5% LZP, 0% for both BRV 100 mg and BRV 200 mg). Conclusions: IV LZP, IV BRV 100 mg, and IV BRV 200 mg showed similar efficacy in controlling acute seizure activity in the EMU. Most patients in all treatment arms were seizure free over 12 hours; numerically higher rescue medication use was observed for patients treated with IV LZP. TEAEs were as expected for each medication. Although this proof of concept trial should be interpreted with caution due to small patient numbers, it suggests a possible role of BRV in the EMU setting; further investigation of efficacy for treatment of acute seizures is warranted. Funding: UCB Pharma-sponsored