Return to full baseline functionality after repeated intermittent use of midazolam nasal spray in patients with seizure clusters: Post hoc analysis of an open-label extension trial

Abstract

Objective: To characterize the time to return to full baseline functionality (RTFBF) in seizure cluster episodes (SCEs) treated with one or two midazolam nasal spray (MDZ-NS/Nayzilam®) doses over the course of repeated intermittent use in patients with seizure clusters (SCs). Methods: Post hoc analysis of an open-label extension trial in patients (≥12 years) with SCs (ARTEMIS-2/P261-402: NCT01529034, 2011-004109-25). Caregivers administered MDZ-NS 5 mg when patients experienced an SC; a second 5-mg dose could be given if seizures did not terminate within 10 min or recurred within 10 min–6 h. Outcomes: time to RTFBF within 24 h of MDZ-NS administration in SCEs treated with one or two doses, overall (all treated SCEs), and by number of treated SCEs for each patient over the course of the trial (Kaplan-Meier analyses). Time to RTFBF was assessed from the time of MDZ-NS administration in SCEs treated with one dose, and from the time of the second dose in SCEs treated with two doses. Results: One thousand nine hundred ninety-six treated SCEs (one dose: 1,201 [60.2%]; two doses: 795 [39.8%]) in 161 patients were evaluable. In SCEs treated with one or two doses, RTFBF within 24 h of MDZ-NS administration was observed in 97.2% and 94.2% of patients; the estimated median time was 1.2 and 1.3 h and stable from 1 to 45 treated SCEs. The RTFBF profile was generally similar in SCEs treated with one or two doses (30% of patients estimated to have RTFBF within 30 min, almost 50% within 1 h); the proportion of patients with RTFBF between 2 and 6h was slightly higher with one versus two doses. Significance: In almost all patients, RTFBF was observed within 24 h of MDZ-NS administration. The median time to RTFBF was similar in SCEs treated with one or two doses, and stable over the course of repeated intermittent use. Thus, dose (5 or 10 mg) does not seem to be a key influencer of time for RTFBF after repeated intermittent use.