Inhaled Alprazolam, a Potential Rescue Medication, Works Rapidly in Patients with Photosensitive Epilepsy

Objective: Evaluate ability of inhaled alprazolam to rapidly suppress photosensitivity in a double blind placebo-controlled crossover proof of concept study. Background: Alprazolam formulated as an inhaled preparation (Staccato Alprazolam ® ) could represent a rapidly effective rescue medication for epilepsy patients. Time to effect can be assessed in patients with photosensitive epilepsy, in whom epileptiform activity can be elicited at will. Design/Methods: Patients ≥ 18 y.o with photosensitive epilepsy at 3 sites were tested on a baseline day, and then received in randomized order either inhaled placebo (on 2 days) or .5, 1 or 2 mg inhaled alprazolam delivered using a hand-held Staccato device. Study days were separated by at least 1 week. Presence (and degree) of photosensitivity was measured predose, then at 2 min, 10 min, 30 min, 1, 2, 4 and 6 hours post-dose. Plasma concentration of study drug was measured at each time point. Sedation was assessed at each time point using the 100-mm linear visual analogue scale (VAS). Results: Five patients were enrolled and completed all treatment arms. All doses decreased the mean standardized photosensitivity range (SPR), with maximal or near-maximal effect occurring by 2 minutes post dose. Higher doses produced effects on SPR out to 4 hours. Sedation was dose related, but separated from SPR effects at later timepoints. Treatment was well tolerated with no serious adverse events. Conclusions: Results from this study suggest that inhaled alprazolam strongly suppresses epileptiform activity within 2 minutes. Duration of effect was dose related, as was sedation. This data supports the possibility that inhaled Alprazolam might have utility in stopping a seizure within 2 minutes of use. Study Supported by: Alexza Disclosure: Dr. French has received personal compensation for activities with Acorda, Adamas, Alexza, Anavex, Biogen, BioPharm Solutions, Cerecor, Concert Pharmaceuticals, Convance, Eisai, Georgia Regents University, GSK, GW Pharma, Marinus, MonosolRx, Monteris, Nestle-Health Science, Neurelis, Novartis, Ovid Therapeutics Inc., Pfizer, Pfizer-Neusentis, Pronutria, Roivant, Sage, SK Life Sciences, Sunovion, Supernus, Takeda, UCB Inc., Upsher Smith, Xenon Pharmaceuticals, Zogenix, Zynerba as a consultant. Dr. Friedman has received personal compensation for activities with LivaNova, Inc., UCB Pharma, GW Pharma, Supernus Pharmaceuticals, NeuroPace, Inc., the Epilepsy Study Consortium, Eisai, Marinus, SK Pharma, Alexza Pharmaceuticals, Pfizer, Upsher-Smith Laboratories, and Zynerba for consulting, participating in the advisory board, or speaking. Dr. Wechsler has received personal compensation for activities with Cyberonics, Eisai, Sunovion, Marinus, and Lundbeck. Dr. DiVentura has received personal compensation for activities with Epilepsy Study Consortium as an employee. Dr. Gelfand has received personal compensation for activities with Antares and Alexza as a consultant. Dr. Pollard has received personal compensation for activities with Cognizance Biomarkers as a part-owner. Dr. Pollard has received research support from Glaxo-Smith Kline, Cognizance Biomarkers, SK Pharmaceuticals, Alexza Pharmaceuticals, Pfizer, and Upsher-Smith Laboratories. Dr. Huie has received personal compensation for activities with Alexza Pharmaceuticals Inc as an employee. Dr. Vazquez has received personal compensation for activities with Eisai, Sunovion, UCB Pharma as a speaker and consultant. Dr. Vazquez has received research support from Acorda Pharma, Alexza Phrama, Neurelis, Inc., Novartis, Pfizer, SK Life Sciences, UCB, and Marinus Pharma. Dr. Gong has received personal compensation for activities with Alexza Pharmaceuticals as an employee. Dr. Cassella has received personal compensation for activities with Alexza Pharmaceuticals as a consultant. Dr. Kamemoto has received personal compensation for activities with Alexza Pharmaceuticals and Dance Pharmaceuticals as an employee and/or consultant.