Abstracts

Rationale: Seizure clusters are emergencies associated with increased risk of prolonged seizures and status epilepticus, requiring prompt treatment to lower the risk of associated morbidities. Need for prompt treatment is reinforced by protocols recommending treatment in seizures lasting ≥5 minutes. Benzodiazepines are the cornerstone of treatment for seizure clusters. Diazepam nasal spray, formulated with Intravail® A3 as an absorption enhancer and vitamin E for solubility, provides a quick, noninvasive, socially acceptable route of administration for acute treatment for seizure clusters in an easy-to-use portable device. Intranasal administration is quicker and avoids social challenges associated with rectal administration. This analysis of a long-term safety study examined the time to administration and ease of use of diazepam nasal spray for patients with epilepsy experiencing seizure clusters.

Methods: The study included patients aged 6–65 years with epilepsy and seizure clusters. Patients and caregivers were trained to administer diazepam nasal spray in age- and weight-based doses of 5, 10, 15, or 20 mg; second doses were to be administered 4–12 hours later if needed. A patient diary was used to record seizure timing, drug administration, and treatment-emergent adverse events (TEAEs). Surveys were distributed to patients and caregivers at study end, completion, or discontinuation to collect data on ease of use of diazepam nasal spray.

Results: Of 175 patients enrolled, 163 received ≥1 dose of study treatment (54.6% female, mean age, 23.1 years; 27 [16.6%] reported self-administration). There were a total of 3853 seizure clusters treated with 4390 doses of diazepam nasal spray. Complete summary of reported time to administration statistics were available for 3627 seizure clusters lasting ≤24 hours (n=162 patients; range 1–143 seizure clusters per patient). Patients received treatment within 2 minutes of the start of 50% of seizure clusters, and 75% were treated within the first 5 minutes. For self-administering patients, 50% were treated within 2 minutes and 75% within 10 minutes. Eighty-four caregivers and 67 patients (including the 27 who self-administered treatment) responded to the exit survey (Table). Administration of diazepam nasal spray was rated extremely or very easy by 93.8% of caregivers and by 77.8% of patients that self-administered. Overall, treatment-related TEAEs were reported for 18.4% of patients (29.6% for patients who self-administered).

Conclusions: These results from the phase 3 safety study of diazepam nasal spray suggest that patients/caregivers reported rapid diazepam administration (75% of seizures treated within 5 minutes). In the survey, ≥75% consider administration extremely or very easy and 40% of surveyed patients reported self-administration. This is meaningful for clinicians, as rapid time to seizure cluster control is critical to reduce morbidity and the risk of progression to status epilepticus and mortality.

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