Randomized open -label trial of intravenous brivaracetam versus lorazepam for acute treatment of increased seizure activity

Objective The objective of the present trial was to assess efficacy and safety of intravenous (IV) brivaracetam (BRV) vs. lorazepam (LZP) in patients with epilepsy undergoing evaluation in an epilepsy monitoring unit (EMU) who experienced seizures requiring acute treatment. Methods This was a phase 2, open-label, randomized, active-control, proof-of-concept trial (EP0087; NCT03021018). Patients (1870years) admitted to EMU were randomized 1:1:1 to single-dose bolus IV LZP (dose per investigator's practice), IV BRV 100mg, or IV BRV 200mg. Trial medication had to be administered within 30min of qualifying seizure. Primary efficacy outcome was time to next seizure (clinical observation with electroencephalogram [EEG] confirmation) or to rescue medication use within 12h of trial medication administration. Secondary outcomes included seizure freedom and rescue medication use within 12h of trial medication administration. Safety and tolerability outcomes included treatment-emergent adverse events (TEAEs). Results Overall, 46 patients were randomized, and 45 received trial medication for a qualifying seizure. Patients in the LZP arm had doses from 1 to 4mg (median: 1mg). Eleven of 45 patients had a seizure within 12h of trial medication administration (LZP 5/15 [median time to next seizure: 5.55h], BRV 100mg 3/15 [5.97h], BRV 200mg 3/15 [3.60h]). No patients received additional rescue medication to control their qualifying seizure. Most patients were seizure-free over 12h (LZP 9/15 [60.0%], BRV 100mg 12/15 [80.0%], BRV 200mg 12/15 [80.0%]). Rescue medication use within 12h was numerically higher for LZP (6/15 [40.0%]) vs. BRV 100mg (1/15 [6.7%]) and vs. BRV 200mg (2/15 [13.3%]). Treatment-emergent adverse events were reported by 5/16 (31.3%), 6/15 (40.0%), and 3/15 (20.0%) of LZP, BRV 100mg, and BRV 200mg patients; one LZP patient had a serious TEAE (seizure cluster). Most common TEAEs (>= 10% of patients) were sedation and somnolence with LZP, and dizziness, headache, and nausea with BRV. Significance Intravenous LZP, IV BRV 100mg, and IV BRV 200mg showed similar efficacy in controlling acute seizure activity in the EMU. Treatment-emergent adverse events were as expected for each medication. Although this trial should be interpreted with caution because of small patient numbers, it suggests a possible role of BRV in the acute treatment of increased seizure activity.