Efficacy and safety of diazepam nasal spray in Japanese Pediatric patients with or at risk for status epilepticus: a phase 3, Multicenter, open-label clinical trial.

Objective: To evaluate the efficacy and safety of diazepam nasal spray (tradename: SPYDIA in Japan, VALTOCO® in the US) following single (Part 1) and multiple (Part 2) dose administrations in pediatric epilepsy patients. Methods: Patients aged 6-17 years with status epilepticus (SE) or at risk for progression to SE despite stable antiseizure medication were eligible. In Part 1, a single intranasal dose (5, 10, or 15 mg) was administered immediately after the onset of a prespecified convulsive seizure. The primary endpoint was the responder rate (seizures ceasing within 10 min post-dose without recurrence for 30 min) in this part. In Part 2, multiple doses were administered for up to 24 weeks to assess efficacy and safety. Results: From November 2022 and January 2024, 22 participants were enrolled in Part 1; 16 were treated. The responder rate was 62.5% (10/16; 95% CI, 35.4-84.8), with the lower CI limit exceeding the 30% threshold. In Part 2, 14 participants treated 91 seizures; 71.4% ceased within 10 min without recurrence for 12 h. Overall, 18 participants received diazepam nasal spray; 14 (77.8%) experienced treatment-emergent adverse events (TEAEs). No TEAEs led to discontinuation, and all treatment-related TEAEs were mild. Treatment satisfaction ("very" or "fairly" satisfied) was reported by 15/16 (93.8%) and 15/17 (88.2%) participants in Parts 1 and 2, respectively. Conclusion: These findings support the favorable efficacy and safety profiles of diazepam nasal spray as a rescue therapy in pediatric patients with or at risk for SE.