Abstracts

Rationale: The Staccato® inhaler aerosolizes a drug and, via inhalation, delivers it deep into the lung for rapid systemic exposure. A proof-of-concept study showed that Staccato alprazolam rapidly suppressed epileptiform activity in photosensitive patients (pts). We present results from a two-part phase 2b study (NCT03478982) exploring feasibility and efficacy of Staccato alprazolam treatment (tx) in pts with predictable seizure patterns (PSP), which include generalized seizures starting with a flurry of absence or myoclonic seizures (abs/MC), prolonged focal seizures (FS), or clusters of ≥2 seizures within 2 h (Cls). Methods: After screening, adult pts (>18 y) with epilepsy enter a qualification period to confirm the frequency of PSPs over 28–56 d (figure). Qualified pts then enter the inpatient tx phase. Pts in Parts 1 and 2 receive a single dose of Staccato tx at the onset of an episode of PSP. Study tx is self-administered, if feasible, or administered by a staff caregiver (SC). Seizure activity is observed by a SC and video EEG. Serum samples are collected pre-dose and 10-, 30-, 60-, 120-, and 360-min post-dose. In Part 1, which is complete, all pts were treated with open-label Staccato alprazolam 1 mg to assess feasibility. In ongoing Part 2, pts are randomized 1:1:1 to double-blind tx with Staccato alprazolam 1 mg or 2 mg, or Staccato placebo. The primary efficacy endpoint is the proportion of responders achieving seizure activity cessation within ≤2 min of tx, with no recurrence of seizure activity ≤2 h. Safety and tolerability are evaluated. Sedation is assessed using the pt visual analogue scale. Results: In Part 1, 8 pts were enrolled and completed open-label tx; all were female, mean age was 48.1 y (range, 24–69), and mean epilepsy duration was 32.3 y (range, 7–63). Pts had PSPs types including 1 abs/MC, 4 FS, and 3 Cls. Dosing during a seizure episode was feasible in all pts. Five pts responded (responder rate, 62.5%). Tx was well tolerated, no pts had serious or severe AEs. Part 2 is ongoing. Of 26 enrolled pts (target enrollment of 115 pts), 24 have received 1 dose of study tx; 18 (75.0%) were female. These pts had the PSP types including 1 abs/MC, 6 FS, and 17 Cls. Dosing during a seizure episode has been feasible in all pts in Part 2. Ongoing safety review has not revealed any concerns. The trial is expected to be complete in October 2019. Conclusions: Feasibility of tx of pts with PSPs was demonstrated in Part 1. Enrollment into Part 2 of the study, the double-blind segment, is ongoing with topline data expected in Fall of 2019. Funding: Engage Therapeutics, Inc.