To assess the impact of treatment of seizure clusters (SCs) with one or two midazolam nasal spray (MDZ-NS) doses on the time to return to full baseline functionality (FBF) in patients with epilepsy, over repeated intermittent episodes.

The time to return to FBF after rescue medication use in patients with SCs is an important factor in assessing the efficacy and tolerability of a SC treatment.

Phase III, open-label extension trial ARTEMIS-2/P261-402 (NCT01529034) evaluated intermittent MDZ-NS use in the treatment of patients (≥12 years) with SCs in the outpatient setting. Caregivers administered a 5-mg dose when patients experienced a SC; a second dose (5 mg) could be given if seizures did not terminate within 10 min or recurred within 6 h post MDZ-NS administration. This post-hoc analysis assessed time to return to FBF within 24 h of MDZ-NS administration (Kaplan-Meier methodology) in SC episodes (SCEs) treated with one or two MDZ-NS doses.

A total of 1996 treated SCEs (one MDZ-NS dose: 1201 [60%]; two doses: 795 [40%]) in 161 patients were evaluable. In SCEs treated with one or two doses, 97.2% and 94.2% of patients returned to FBF within 24 h of MDZ-NS administration, respectively; the estimated median time was 1.2 h (Q1–Q3: 0.4–2.4) and 1.3 h (0.5–3.5), respectively. The profile of return to FBF was generally similar in SCEs treated with one and two MDZ-NS doses, with a slightly higher proportion of patients returning to FBF between 2–6 h after the administration of one MDZ-NS dose.

The vast majority of patients returned to FBF within 24 h of intermittent administration of one or two MDZ-NS doses, with a similar median time to return to FBF. These return to FBF data further support the favorable profile of repeated intermittent MDZ-NS use in patients with SCs.