A peer-reviewed study published in Epilepsia (October 2025) evaluated the pharmacokinetics, safety, and tolerability of single-dose Staccato® alprazolam in adolescents with epilepsy. The findings support appropriate dose selection for adolescents aged 12–17 years, contributing important evidence toward the clinical development of rapid-acting rescue therapies for seizure management .
Addressing the Need for Rapid-Acting Seizure Rescue Therapies
Epilepsy affects millions worldwide, including a significant pediatric and adolescent population. While many patients achieve seizure control with maintenance therapies, acute seizure episodes remain a serious concern. Rapid delivery of rescue medication is critical to limit seizure duration and prevent escalation.
Staccato® alprazolam is a novel, hand-held inhalation device designed to deliver alprazolam rapidly through the intrapulmonary route, allowing for fast systemic absorption compared to traditional oral formulations.
About Staccato® Alprazolam
Staccato® alprazolam combines:
- A breath-actuated inhalation device
- Rapid pulmonary drug delivery
- Quick onset of systemic exposure
This technology aims to provide fast-acting benzodiazepine therapy for seizure emergencies while maintaining a simple, portable administration method.
Study Objective and Design
The primary objective of this Phase 1, multicenter, open-label trial was to evaluate the pharmacokinetics (PK) and tolerability of a single 2 mg dose of Staccato® alprazolam in adolescents with epilepsy. PK data were also incorporated into a population pharmacokinetic analysis to support dose selection for upcoming Phase 3 trials .
Study Population
- Adolescents aged 12–17 years
- Diagnosed with focal, generalized, or combined epilepsy
- Study identifier: UP0100 / NCT04857307
A total of 14 patients were enrolled:
- 6 patients weighing <50 kg
- 8 patients weighing ≥50 kg
Participants received a single 2 mg dose in the morning after an overnight fast.
Key Pharmacokinetic Findings
Analysis of plasma alprazolam concentrations demonstrated:
- Rapid absorption, with a median time to maximum concentration (Tmax) of 10.5 minutes
- Linear elimination across participants
- Similar pharmacokinetic profiles across body weight groups
Key PK parameters—including Cmax, AUC₀–t, AUCinf, and apparent total body clearance (CL/F)—were comparable between adolescents weighing under and over 50 kg .
Population PK simulations further indicated that:
- Overall exposure (AUCinf) in adolescents receiving 2 mg was similar to adult reference ranges
- A slight increase in Cmax was observed in lower body weight participants, without clinical safety concerns
Safety and Tolerability
Staccato® alprazolam was well tolerated in this adolescent population. Reported treatment-emergent adverse events (TEAEs) were mild and included:
- Dysgeusia
- Somnolence
- Dizziness
- Cough
- Hiccups
No severe or serious adverse events were reported, and no clinically meaningful safety differences were observed between weight groups .
Clinical Significance
The study findings support the use of Staccato® alprazolam 2 mg in adolescents with epilepsy, demonstrating:
- Rapid systemic absorption
- Consistent pharmacokinetics across body weights
- Favorable tolerability profile
These results provide important justification for using a fixed 2 mg dose in adolescents and support continued evaluation in Phase 3 clinical trials.
Academic and Collaborative Impact
The study reflects collaboration across leading epilepsy centers and academic institutions, including Hawaii Pacific Neuroscience, where Kore Kai Liow, MD contributed as a co-author. The publication underscores Hawaiʻi’s role in advancing epilepsy research with global clinical impact.
