The long-term safety of Valtoco® (diazepam nasal spray), which is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years, evaluated repeated doses in a 12-month phase 3 open-label study.

Benzodiazepines are the mainstay of rescue therapy for seizure clusters. Diazepam nasal spray is a proprietary formulation with n-dodecyl beta-D-maltoside and vitamin E.

Care partners and patients were trained to administer doses of 5, 10, 15, or 20 mg, based on age and weight; if needed, a second dose was administered 4–12 hours later. Seizures, drug administration, and treatment-emergent adverse events (TEAEs) were recorded in diaries. Study visits included physical/neurological examinations, vital signs, and laboratory tests.

Of 175 patients enrolled, 163 received diazepam nasal spray (mean age 23.1 years; range: 6–65; 4053 total seizures). The majority of patients (81.6%) had duration of exposure ≥12 months; 52.8% of patients averaged ≥2 doses per month. A total of 134 (82.2%) patients had ≥1 TEAE. Serious TEAEs were recorded in 50 (30.7%) patients; none was deemed treatment-related. TEAEs assessed as being possibly treatment-related were seen in 30 (18.4%) of patients, most commonly nasal discomfort (6.1%). Of note, there were no TEAEs of cardiac or respiratory depression. There were no trends in vital signs or laboratory tests. Of 46 patients who discontinued, 19 withdrew, 11 were lost to follow-up, 1 died (not deemed treatment related), 1 discontinued to due adverse event (not deemed treatment-related), and 14 discontinued for other reasons.

In this phase 3 long-term, repeated dosing safety study of diazepam nasal spray for patients with seizure clusters, safety was consistent with the established profile of diazepam. Treatment-related TEAEs were reported in 18.4% of patients. Exposure was ≥12 months in 81.6% of patients, and retention rate was high (71.8% [117/163]).