Staccato Alprazolam Shows efficacy and Tolerability for rapid termination of seizures in Phase 1 Studies
Staccato® alprazolam is a novel drug-device combination designed to deliver alprazolam to the deep lung for the rapid termination of seizures. Two phase 1 studies evaluated its pharmacokinetics (PK) and safety profile in healthy adult participants. This article presents the findings from these studies. This study was published in the journal Epilepsia. The study was conducted by Yoshinobu H. and colleagues.
Alprazolam is commonly used to treat anxiety and panic disorders, but its rapid absorption and distribution via inhalation make it a potential candidate for seizure termination. The Staccato device delivers a single-use, inhaled dose of alprazolam, offering a promising approach for rapid seizure control.
The smoker study (EPK-002/NCT03516305) involved 36 participants aged 21–50 years, including smokers and nonsmokers, who received a single inhaled dose of 1 mg Staccato alprazolam. The ethnobridging study (UP0101/NCT04782388) included Japanese, Chinese, and Caucasian participants aged 18–55 years who were randomized to receive a single inhaled dose of Staccato alprazolam 2 mg or placebo.
The key findings of the study were as follows:
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Rapid Absorption: Alprazolam was rapidly absorbed, with a median time to peak plasma concentration (Tmax) of 1.5–2 minutes post-dose in both studies.
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This rapid absorption was consistent across smokers, nonsmokers, and participants of different ethnicities.
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Similar Absorption in Smokers and Nonsmokers: Staccato alprazolam was absorbed to a similar extent in both smokers and nonsmokers, indicating consistent pharmacokinetics regardless of smoking status.
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Tolerability: The most commonly reported treatment-emergent adverse events (TEAEs) were somnolence and dizziness, with no serious or severe TEAEs reported.
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Staccato alprazolam demonstrated a safety profile consistent with other alprazolam formulations, with no new safety signals identified.
The phase 1 studies of Staccato alprazolam demonstrated rapid absorption, reaching therapeutic drug levels within 2 minutes post-dose. The drug was well tolerated across different populations, including smokers and individuals of various ethnicities. These findings support further investigation of Staccato alprazolam as a potential treatment for rapid seizure termination.
Reference:
Hayakawa, Y., Rospo, C., Bartmann, A. P., King, A., Roebling, R., & Chanteux, H. (2024). Pharmacokinetics of Staccato® alprazolam in healthy adult participants in two phase 1 studies: An open‐label smoker study and a randomized, placebo‐controlled ethnobridging study. Epilepsia. https://doi.org/10.1111/epi.17901
