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.