Abstracts

Rationale:
It is clinically relevant to understand whether the effectiveness and safety of benzodiazepine seizure cluster rescue therapy may be affected by concomitant use of maintenance benzodiazepines as part of an antiseizure drug (ASD) regimen. Diazepam nasal spray (Valtoco®), a proprietary formulation indicated for acute treatment of seizure clusters in patients with epilepsy aged 6 years and older, is designed to be a rapid, noninvasive, and socially acceptable route of administration. Interim analysis results of a phase 3 trial of diazepam nasal spray in patients receiving concomitant benzodiazepines are presented.
Method:
The study enrolled patients with epilepsy who had seizures despite a stable ASD regimen. Patients and caregivers were trained to administer diazepam nasal spray 5, 10, 15, or 20 mg (age- and weight-based), with a second dose, if needed, 4 to 12 hours later. This analysis evaluated diazepam nasal spray utilization and safety profile in patients with and without concomitant use of maintenance benzodiazepines, including alprazolam, clobazam, clonazepam, clorazepate, diazepam, lorazepam, and midazolam.
Results:
Of 177 patients enrolled, 158 received diazepam nasal spray (aged 6–65 years; 53.8% female; 82.3% white). Of those, 119 (75.3%) were using concomitant benzodiazepines as part of their ASD regimen; 39 (24.7%) were not (Table 1). Most patients in both groups had a duration of diazepam nasal spray exposure ≥12 months (with concomitant benzodiazepines, 90 [75.6%]; without, 26 [66.7%]). A higher proportion in the concomitant benzodiazepine subgroup received ≥2 doses of diazepam nasal spray/month on average (58.8% vs 48.7%) (Table 1). The percentage of seizure episodes using a single dose of diazepam nasal spray, as a proxy for effectiveness, was similar for those with concomitant benzodiazepines (90.5%) and those without (92.4%). The proportions of patients with treatment-emergent adverse events (TEAEs) were higher for those with concomitant benzodiazepines (79.8%) than those without (61.5%) (Table 2). Serious TEAEs were higher among the patients using concomitant benzodiazepines (30.3% vs 23.1%), but none of the serious TEAEs was deemed related to treatment. The most common TEAEs generally had a higher incidence in the concomitant benzodiazepines subgroup (Table 2), including seizure, pyrexia, and nasopharyngitis. Retention rate was 84.1% with concomitant benzodiazepines and 76.9% without.
Conclusion:
Results from this long-term study suggest that the effects of diazepam nasal spray are similar no matter whether patients concomitantly use other benzodiazepines as part of their daily ASD regimen. In most cases, the number of doses used for seizure activity was independent of the presence of concomitant benzodiazepines, and no difference in retention rate was seen. The safety profile of diazepam nasal spray was consistent with what may be expected for diazepam.
Funding:
:Neurelis, Inc.