(553) Time to Second Doses in Emergency Seizure Patients Treated With Valtoco® (diazepam nasal spray) Across 24 Hours: Interim Subgroup Results From a Phase 3, Open-label, Repeat Dose Safety Study

Rationale: Seizure clusters may persist 24 hours or longer, and rescue therapies for seizure clusters that provide long-lasting activity are needed. However, few data are available for rescue therapies across a full 24 hours after the start of the cluster. Diazepam nasal spray (Valtoco^®), approved for acute treatment of seizure clusters in patients with epilepsy aged six years or older, is being studied in a long-term, open-label, repeat dose safety study. Presented here is a post hoc analysis from that study to assess the need for a second dose up to 24 hours after the first dose.

Methods: The study enrolled patients aged six to 65 years with frequent seizure clusters. Age- and weight-based doses (5, 10, 15, or 20 mg) of diazepam nasal spray were administered by caregivers or patients. Per protocol, if needed to control a seizure cluster, second doses were to be administered four to 12 hours after the first dose. Patients received second doses per guidance and based on the investigator’s interpretation that those doses were needed. Seizures, doses, and time of administration were recorded in a diary. Times to second doses were analyzed at 4, 6, 8, 12, 16, 20, and 24 hours after the initial doses.

Results: As of October 31, 2019, the study enrolled 177 patients, 158 of whom received diazepam nasal spray treatment for 3370 seizure clusters. Treated patients were 53.8% female, 82.3% white, and had a mean age of 23.5 years (range: 6–65). Exposure was ≥12 months in 73.4% of patients, 6 to < 12 months in 19.6%, and < 6 months in 7.0%; 56.3% of patients averaged ≥2 doses/month. Among these treated patients, 76 (48.1%) received a second dose for 439 (13%) seizure cluster episodes. Recorded seizure events and treatments were virtually identical; thus, the treatment number also reflects the documented need for second doses. 
Demographics and treatment duration for the second-dose subgroup were similar to the overall treated population. Among the second-dose subgroup, within 4 hours, 142 (4%) clusters were treated with a second dose (n=39 patients); within 6 hours, 210 (6%, n=48); within 12 hours, 296 (9%; n=62); and 439 (13%; n=76) clusters were treated across the full 24 hours (Figure). Adverse events (AEs) were reported for 119 (75.3%) patients overall. AEs considered treatment-related were reported in 26 (16.5%) patients, with only nasal discomfort occurring in >5% of patients (n=9; 5.7%); none were considered serious. Twenty-seven (14.8%) patients discontinued the study, none of these were due to an AE.

Conclusions: The need for a second dose of diazepam nasal spray was low throughout the 24-hour period after a seizure cluster had started, with a second dose administered for only 13% of seizure clusters. These data support patients’ maintenance of control over 24 hours after the initial diazepam nasal spray dose. The retention rate in the study was high.

Funding: Please list any funding that was received in support of this abstract.: Neurelis, Inc.
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