Alprazolam delivered by Staccato device effective for rapid control of seizures

A recent article published in Epilepsia Journal suggests that staccato alprazolam doses, both 1.0 mg and 2.0 mg were effective in promptly ending seizures in an inpatient environment and were well tolerated.

Alprazolam injected into the deep lung through the Staccato® breath-actuated device for fast systemic exposure is a promising therapeutic for quick epileptic episode termination (REST). In order to determine whether Staccato alprazolam rapidly terminates seizures in a small observed population after administration under direct supervision, Jacqueline French and colleagues conducted an inpatient study (ENGAGE-E-001 [NCT03478982]) in patients with stereotypic seizure episodes with prolonged or repetitive seizures.

Adult patients having a confirmed diagnosis of focal and/or generalized epilepsy and a documented history of seizure episodes with a predictable pattern were included in the study. In an inpatient facility, they were randomized 1:1:1 to double-blind treatment of a single seizure occurrence with one dosage of Staccato alprazolam 1.0 mg or 2.0 mg, or Staccato placebo. The primary end objective of the trial was the proportion of responders in each treatment group who experienced seizure activity cessation within 2 minutes of receiving the study medication and no return of seizure activity after 2 hours.

The key findings of this study were:

1.In the double-blind portion, 273 individuals were screened, and 116 randomized participants got therapy with the study medication.

2.The proportion of treated patients who responded to Staccato alprazolam 1.0 mg (n = 38; p =.0392) and 2.0 mg (n = 38; p =.0392) was 65.8%, compared to 42.5% for Staccato placebo (n = 40).

3.When delivered as a single dosage of 1.0 or 2.0 mg, staccato alprazolam was well tolerated: cough and somnolence were the most prevalent adverse effects (AEs) (both 14.5%), followed by dysgeusia (13.2%).

4.The majority of the adverse events (AEs) were mild to moderate in severity; there were no treatment-related significant AEs.

In conclusion, this proof-of-concept research found that 1.0 mg and 2.0 mg dosages of Staccato alprazolam were both effective and well tolerated in promptly ending seizures in a limited observed group in an inpatient environment. The next step will be a larger Phase 3 outpatient confirmatory research to show the effectiveness and safety of Staccato alprazolam for quick seizure cessation in an outpatient environment among patients 12 years of age and older with stereotyped protracted seizures.

Reference:

French, J., Biton, V., Dave, H., Detyniecki, K., Gelfand, M. A., Gong, H., Liow, K., O'Brien, T. J., Sadek, A., DiVentura, B., Reich, B., & Isojarvi, J. (2022). A randomized phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato® alprazolam for rapid seizure termination. In Epilepsia. Wiley. https://doi.org/10.1111/epi.17441