Abstracts

Rationale: Nayzilam™ (USL261; midazolam nasal spray) has been developed as an alternative to rectal diazepam, the only FDA-approved non-intravenous treatment for patients with intermittent bouts of increased seizure activity (ie, acute repetitive seizures [ARS], seizure clusters [SC]). The safety and efficacy of Nayzilam were evaluated in a randomized, double-blind, placebo-controlled, global, phase 3 study (ARTEMIS-1; NCT01390220). Methods: ARTEMIS-1 consisted of 2 phases, an in-clinic Test Dose Phase (TDP) and an outpatient Comparative Phase (CP). During the TDP, subjects with a history of SC receiving a stable regimen of antiepileptic drugs (AED) received 2 doses of open-label Nayzilam 5 mg administered 10 minutes apart at the study center. The TDP was followed by the CP where subjects were randomized (2:1) to receive Nayzilam 5 mg or placebo (PBO). The subject’s caregiver administered the double-blind study drug when the subject experienced a SC meeting study criteria. A second, open-label Nayzilam 5 mg dose could be administered between 10 minutes and 6 hours after the first dose for persistent or recurrent seizure activity. Safety and tolerability were evaluated through adverse event monitoring, vital sign measurements, and clinical laboratory evaluations. Results: All subjects who received study drug during the TDP (n=292 Nayzilam) and CP (n=134 Nayzilam; n=67 PBO) were included in these analyses. Of the 16 subjects who discontinued from the study due to an adverse event (AE) during the TDP, 13 discontinued for AEs considered related to study drug by the investigator and most were related to the route of administration and/or protocol defined withdrawals. No subject discontinued from the study due to an AE during the CP. The overall incidence of treatment emergent AEs (TEAEs) was 51% (Nayzilam) during the TDP, and 28% (Nayzilam) and 22% (PBO) during the CP, with the majority reported as mild-to-moderate in intensity. Nasal discomfort, somnolence, lacrimation increased, product taste abnormal, and throat irritation were the most commonly reported treatment-related TEAEs throughout the study. No deaths were reported. Fourteen (4.8%) and 2 (1.0%) subjects reported at least one treatment-emergent serious AE during the TDP and CP, respectively, of which 3 (1.0%) during the TDP and 0 during the CP were considered related to study drug by the investigator. No abnormal trends in safety evaluations were observed. Conclusions: Nayzilam appeared to be safe and well-tolerated in subjects with seizure clusters. Adverse events were generally consistent with the route of administration and pharmacology of the drug. These data suggest that Nayzilam may provide a significant benefit to patients with epilepsy. Funding: Proximagen, LLC