(563) Characteristics of Patients Who Self-Administered Diazepam Nasal Spray for Seizure Clusters: Interim Results From a Phase 3, Open-label, Repeat Dose Safety Study

Rationale: The potential for self-administration of intranasal benzodiazepine rescue therapy for seizure clusters may provide patients with more control. Diazepam nasal spray (Valtoco^®), a proprietary intranasal formulation indicated for acute treatment of seizure clusters in patients with epilepsy aged six years and older, is designed to be a convenient, rapid, noninvasive route of administration, with a device similar to that used for some self-administered intranasal therapies. Results from a survey of patients who self-administered diazepam nasal spray are presented.

Methods: Diazepam nasal spray was evaluated in a Phase 3 safety study of patients aged six to 65 years with seizure clusters. Patients and caregivers were trained in administration of age- and weight-based doses of 5, 10, 15, or 20 mg; self-administration was not excluded. Safety was assessed. A survey was given to patients and caregivers at the study end and was mailed to those who had already completed or dropped out.

Results: Of 177 patients enrolled at the October 31, 2019, interim cutoff, 158 received diazepam nasal spray and were evaluated in the safety population. Surveys were returned by 67. A subgroup of 27 self-administered diazepam nasal spray (Figure 1). Of those 27, the median age was 34 (range: 11–65) years, 55.6% were female, 81.5% were white. Doses received were 10 mg, 2 (7.4%); 15 mg, 10 (37.0%); and 20 mg, 15 (55.6%). In this subgroup, a total of 994 doses were administered: 10 mg, n=61 (6.1%); 15 mg, n=180 (18.1%); and 20 mg, n=753 (75.8%), with a low rate of dosing errors (11 [1.1%]). Twenty-six patients in this subgroup had diazepam nasal spray exposure ≥ 12 months.Self-administering patients were asked when they primarily administered diazepam nasal spray. Twenty-five of the 27 patients responded to this question (Figure 2); the most common response was, “At the first signs that a seizure may be coming” (48%, n=12).The safety profile of self-administering patients was similar to the full population. Twenty patients (74%) had a treatment-emergent adverse event (TEAE). Six (22%) had a serious TEAE, with none considered treatment-related. No patients discontinued due to a TEAE. Six patients (22%) had TEAEs that were possibly treatment-related, with only nasal discomfort (15%, n=4 [3 mild, 1 moderate]) in > 2%.

Conclusions: These results support self-administration of diazepam nasal spray consistent with the approved label, representing an improvement over other routes of administration that require a care provider. Nearly half of these patients reported primarily administering diazepam nasal spray at the first signs that a seizure cluster was coming. The patient responses suggest they were taking steps to self-control their treatment. They reported ease of use. The safety profile in these patients was consistent with the entire study population, with no discontinuations due to TEAEs. Nasal discomfort was present in 15% of patients and was mostly mild and transient.

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