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Inhaled alprazolam rapidly suppresses epileptic activity in photosensitive participants
Author(s) -
French Jacqueline A.,
Wechsler Robert,
Gelfand Michael A.,
Pollard John R.,
Vazquez Blanca,
Friedman Daniel,
Gong Lily H.,
Kamemoto Edwin,
Isojarvi Jouko,
Cassella James V.
Publication year - 2019
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16279
Subject(s) - alprazolam , somnolence , medicine , anesthesia , placebo , sedation , epilepsy , discontinuation , adverse effect , dysgeusia , psychology , anxiety , psychiatry , alternative medicine , pathology
Objective Treatment options for seizure clusters are limited; the need for easy‐to‐administer treatments remains. The Staccato system delivers drug deep into the lung via inhalation. In this phase 2a study, we investigated the ability of three different doses of Staccato alprazolam to suppress the electroencephalographic ( EEG ) photoparoxysmal response ( PPR ) compared with placebo in participants with photosensitive seizures. Methods Adults (18‐60 years) with a diagnosis and history of PPR on EEG with or without an epilepsy diagnosis were eligible to participate. Participants received Staccato alprazolam 0.5, 1.0, and 2.0 mg, and Staccato placebo (twice) in random order. Intermittent photic stimulation and clinical assessments were performed at one predose and seven postdose time points. The primary endpoint of the study was the change in standardized photosensitivity range ( SPR ) in participants receiving each dose of Staccato alprazolam. Results Fifteen participants with a prior epilepsy diagnosis were screened; five were enrolled, randomized, and completed the study. All participants were white females with a mean ( SD ) age of 27.2 (6.8) years. All doses of Staccato alprazolam reduced the SPR at 2 minutes; the effect was sustained through 4 hours for the 0.5‐mg dose and 6 hours for the 1.0‐ and 2.0‐mg doses. The magnitude and duration of sedation and sleepiness were dose‐related. Four participants (80%) experienced ≥1 adverse event ( AE ); none was severe or serious. Cough, diarrhea, dysgeusia, oral dysesthesia, sedation, and somnolence were experienced by two participants (40%) each. Significance This proof‐of‐concept study demonstrated that Staccato alprazolam 0.5, 1.0, and 2.0 mg rapidly suppressed epileptiform activity in photosensitive participants with epilepsy. The AE profile of Staccato alprazolam was similar to what has been reported for alprazolam for other indications. The results support further development of Staccato alprazolam as a rescue medication for the acute treatment of seizures.