To present results from the ongoing randomized, double-blind, phase 2b, in-patient study (NCT03478982) exploring the efficacy and safety of Staccato® alprazolam (STAP) in the acute termination of a predictable seizure pattern (PSP): a prolonged focal, generalized, or cluster seizure episode.

The Staccato inhaler aerosolizes a drug and a normal inhalation delivers it deep into the lung for rapid systemic exposure. A proof-of-concept study showed that Staccato alprazolam rapidly suppressed epileptiform activity in photosensitive patients.

Eligible patients (>18 years) with epilepsy entered a qualification period to confirm the frequency of PSPs over 28–56 days. Qualified patients were admitted to the epilepsy monitoring unit and randomized 1:1:1 to double-blind treatment with STAP 1 mg or 2 mg, or Staccato placebo. Study treatment was self-administered, if feasible, or administered by a staff caregiver (SC) at the onset of seizure activity; patients were observed by a SC and video EEG. The primary efficacy endpoint was the proportion of responders achieving seizure activity cessation within 2 minutes of treatment and no recurrence within 2 hours. Safety and tolerability were evaluated.

As of 4 October 2019, 74 patients received 1 dose of study treatment. Overall, patient mean age was 34.4 years (range 18–66), and 62% were female. Patients had the following PSP types: n=4 generalized starting with flurry of absence or myoclonic lasting >5 minutes, n=23 prolonged focal lasting >3 minutes, and n=47 cluster of ≥2 within 2 hours. Dosing during a seizure episode has been feasible in almost all patients. All AEs have been mild or moderate; dysgeusia (14%) was the most commonly reported AE. Responses have been observed across all PSP types.

Treatment of ongoing seizures with STAP or placebo has been feasible. Topline unblinded results are expected in Spring of 2020.