- Compared with placebo, nasal midazolam spray provided rapid, sustained seizure control in patients with seizure clusters with a good safety profile.
Why this matters
- Limited options for treating seizure clusters outside of medical settings by nonclinicians.
- Compared with placebo group, nasal midazolam group had:
- Higher rate of treatment success (53.7% vs 34.3%; P=.0109).
- Lower rate of seizure recurrence (38.1% vs 59.7%; P=.0043).
- Longer time to next seizure (probability of no seizure at 24 hours, 58.3% vs 37.1%; P=.0124).
- During double-blind phase, midazolam and placebo groups similar on:
- Treatment-emergent adverse events (26.4% vs 23.1%).
- Discontinuation due to treatment-emergent adverse events (0% vs 0%).
- Leading treatment-emergent adverse events with midazolam during double-blind phase: somnolence (9.9%), headache (6.6%), nasal discomfort (5.5%).
- International phase 3 randomized controlled trial: 292 patients aged ≥12 years on a stable regimen of antiepileptic drugs for seizure clusters (ARTEMIS‐1 trial).
- After in-clinic test dose phase, randomized 2:1 to 6-month double-blind phase: midazolam nasal spray 5 mg vs placebo nasal spray, administered by caregivers for seizure cluster.
- Main outcome: treatment success (seizure termination within 10 minutes and no recurrence 10 minutes to 6 hours thereafter).
- Funding: Proximagen LLC.
- Trial stopped early.
- No active comparator.