Staccato Alprazolam Suppresses Epileptic Activity in Phase 2a Study

A phase 2a proof-of-concept study (NCT02351115) demonstrated that Staccato alprazolam 0.5 mg, 1 mg, and 2 mg, rapidly suppressed epileptiform activity in photosensitive subjects with epilepsy, further supporting its development as a rescue medication for acute treatment of seizures.

All doses of Staccato alprazolam reduced the standardized photosensitivity range at 2 minutes. The effect was sustained for the 0.5 mg dose through 4 hours and 6 hours for the 1 mg and 2 mg doses.

“When you give a drug by a nasal preparation, it has to go across the mucus membrane and has to get into the blood stream and the brain. That all takes usually somewhere around 10 minutes, and 10 minutes doesn’t sound like a lot, but when you’re about to have a seizure, 10 minutes is an eternity. So what could we do to shorten that time where people might have a seizure or multiple seizures,” lead author Jacqueline French, MD, professor of neurology and director of translational research and epilepsy clinical trials, NYU Langone, and Chief Medical Innovation Officer, Epilepsy Foundation, told NeurologyLive. “It turns out that there was a company that was working on an inhaler that gets drug not to the mucus membrane of the nose or there’s also rectal preparations of rescue, but to the lung where you have an enormous quantity of space for the drug to be absorbed and you can measure the serum concentrations and even at 2 minutes there is a very high concentration in the blood stream and in the brain.”

Investigators evaluated the ability of the 3 different doses of Staccato alprazolam to suppress the electroencephalographic (EEG) photoparoxysmal response (PPR) compared with placebo in 5 adult patients with a prior diagnosis of PPR on EEG. All participants were white females with a mean age of 27.2 years.

The primary outcome measure was the change in standardized photosensitivity range in participants receiving each dose of Staccato alprazolam, while secondary endpoints included the assessment of sedation and somnolence, the correlation of plasma concentrations of Staccato alprazolam with pharmacodynamic effects on sedation, the assessment of adverse effects and changes in the neurological examination, and the time to onset of effect.

Efficacy outcome measures included the pharmacodynamic and pharmacokinetics assessments and PPR evaluations; safety evaluations included adverse effects, clinical laboratory assessments, and sedation assessments.

The adverse effect profile was similar to that alprazolam for other indications. Four of the 5 participants experienced at least 1 adverse effect during the study. Adverse effects were mild or moderate in severity and no serious adverse effects were reported. The incidence of adverse effects was greater in the Staccato alprazolam 2-mg treated period. Cough, diarrhea, dysgeusia, oral dysesthesia, sedation, and somnolence were experience by 2 participants each.

This study showed that treatment with all 3 doses of Staccato alprazolam rapidly suppressed epileptic activity at the earliest measurable time point of 2 minutes. These results support further development as a potential rescue medication.

NeurologyLive previously spoke with French, the principal investigator, to discuss the promising findings of Staccato alprazolam which serve as the foundation for advancing this therapy as a potential rescue medication for the acute treatment of seizures.

REFERENCE

French J, Wechsler R, Gelfand M, et al. Inhaled alprazolam rapidly suppresses epileptic activity in photosensitive participants. Epilepsia. 2019. doi: 10.1111/epi.16279.