To evaluate the efficacy and safety of inhaled alprazolam (Staccato^® Alprazolam) in patients with epilepsy with predictable seizure patterns.

Staccato Alprazolam was previously shown to have a rapid onset of effect in an intermittent photic stimulation epilepsy study. We now use patients with predictable seizure patterns to evaluate the rapid onset of effect in a clinical setting.

Part 1 of this inpatient, phase 2b study [NCT03478982] was open-label feasibility testing of 1 mg Staccato Alprazolam in eight patients with epilepsy with predictable seizure episodes. Each patient was treated with one dose of Staccato Alprazolam at the onset of their predictable episode. Patients with seizure-activity cessation within 2 minutes of treatment administration and no recurrence within 2 hours were defined as responders.

Eight patients were enrolled and completed the open-label portion; all were female, mean age was 48.1 years (range, 24–69), and mean epilepsy duration was 32.3 years (range, 7–63). The most common background AEDs were levetiracetam, lacosamide, zonisamide, and pregabalin. Seven patients had focal seizures and 1 had generalized seizures. Patients had the following predictable seizure episodes: 1 had generalized seizures starting with a flurry of absence or myoclonic seizures (≥5-minute duration after recognition); 4 had episodes of a prolonged focal seizure (≥3-minute duration); and 3 had ≥2 seizures within 2 hours. Dosing during a seizure episode was feasible in all patients. Five patients responded (responder rate, 62.5%). Although safety analysis is still ongoing, no adverse events were serious or severe.

Dosing with 1 mg Staccato Alprazolam was feasible in patients with predictable seizure episodes. The treatment appeared efficacious and well tolerated. The study will continue to part 2 (double-blind), which will randomize 100 patients to one of two active arms (1 mg or 2 mg Staccato Alprazolam) vs placebo.