Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open‐label extension trial

Abstract

To evaluate safety- and seizure-related outcomes with repeated intermittent use of a novel formulation of midazolam administered as a single-dose nasal spray (MDZ-NS) in the outpatient treatment of patients experiencing seizure clusters (SCs). In this open-label extension trial (ClinicalTrials.gov NCT01529034), patients aged ≥12years and on a stable regimen of antiepileptic drugs who completed the original phase III, randomized controlled trial were enrolled. Caregivers administered MDZ-NS 5mg when patients experienced SCs; a second dose could be given if seizures did not terminate within 10minutes or recurred within 10minutes-6hours. Patients were monitored for treatment-emergent adverse events (TEAEs) throughout, and the main seizure-related outcome was treatment success, defined as seizure termination within 10minutes and no recurrence 10minutes-6hours after drug administration. Of 175 patients enrolled, 161 (92.0%) received ≥1 MDZ-NS dose, for a total of 1998 SC episodes. Median time spent by patients in the trial was 16.8months (range = 1-55.7months). TEAEs were experienced by 40.4% of patients within 2days of drug administration and 57.1% overall. TEAEs reported by most patients (within 2days and overall) were nasal discomfort (12.4%) and somnolence (9.3%). One patient each discontinued due to treatment-related nasal discomfort and somnolence. There were no patients with treatment-related respiratory depression, and none with TEAEs indicative of drug abuse or dependence. Treatment success criteria were met in 55% (1108/1998) of SC episodes after administration of a single 5-mg dose and in 80.2% (617/769) with the second dose. Treatment success was consistent over treated episode number. Repeated, intermittent, acute treatment of patients experiencing SCs with MDZ-NS in the outpatient setting was well tolerated over an extended period, with maintenance of efficacy suggesting lack of development of tolerance.