This analysis assessed the use of a second dose of diazepam nasal spray (Valtoco®) for acute treatment of seizure clusters up to 24 hours after the first dose.

Seizure clusters may persist ≤24 hours, and rescue therapies that provide long-lasting activity are needed. Diazepam nasal spray, approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years, was studied in a long-term, open-label, repeat dose safety study.

Patients aged 6 to 65 years with frequent seizure clusters were enrolled. Age- and weight-based doses (5, 10, 15, or 20 mg) of diazepam nasal spray were administered, with patients and care partners instructed to give second doses 4 to 12 hours later, if needed. Second doses are reported at 4, 6, 12, and 24 hours after the initial dose.

The completed study enrolled 175 patients; 163 (54.6% female; mean age, 23.1 years [range, 6–65]) received diazepam nasal spray for 4053 seizures. Exposure was ≥12 months in 81.6% of patients.

A second dose was used for 485 (12.0%) seizure episodes. Second doses were used in 4 hours for 152 (3.8%) episodes; in 6 hours for 224 (including prior patients; 5.5%); in 12 hours for 318 (7.8%); and in 24 hours for 485 (12.0%). Treatment-emergent adverse events (TEAEs) were reported for 82.2% of patients. Treatment-related TEAEs were reported in 18.4%; none were serious. Forty-six (26.3%) patients discontinued, with one due to an AE (not considered treatment related).

In this phase 3, open-label, repeat dose safety study, a second dose was administered for 12.0% of seizure episodes in highly intractable epilepsy patients experiencing seizure clusters. These data suggest patients’ maintenance of control over 24 hours after the initial diazepam nasal spray dose. The retention rate in the study was high.