(135) 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

Rationale: The time to return to full baseline functionality (FBF) after use of rescue medication is an important factor in assessing the efficacy of treatment for seizure clusters (SCs). In a Phase III, open-label extension trial (P261-402; NCT01529034) that evaluated safety and efficacy of repeated intermittent use of midazolam nasal spray (MDZ‐NS) in the outpatient treatment of patients (≥12 years) with SCs, patients returned to FBF within 24 h of administration of the first dose of MDZ‐NS in most SC episodes (SCEs), with a median time of 1.2 h (Wheless et al. Epilepsia 2019). The objective of this analysis was to assess the influence of treatment with 1 or 2 MDZ-NS doses on the time to return to FBF.

Methods: Post hoc analysis of Phase III, open-label extension trial (P261-402). Caregivers administered MDZ‐NS 5 mg when patients experienced a SC; a second dose could be given if seizures did not terminate within 10 min or recurred within 10 min–6 h. In this post hoc analysis, time to return to FBF within 24 h of MDZ-NS administration (documented by caregiver) was assessed in SCEs treated with one or two MDZ-NS doses, overall (all SCEs treated) and over time (by number of SCE treated) using Kaplan-Meier method. Time to return to FBF was assessed from the time of MDZ-NS administration in SCEs treated with 1 dose and from the time of the second MDZ-NS dose in SCEs treated with 2 doses.

Results: Overall, 1996 SCEs treated with MDZ-NS in 161 patients were evaluable (1201 [60%] treated with 1 dose; 795 [40%] with 2 doses). In SCEs treated with one or two MDZ-NS doses, patients returned to FBF within 24 h of MDZ-NS administration in 97.2% and 94.2% of SCEs, with an estimated median time of 1.2 h (Q1–Q3: 0.4–2.4) and 1.3 h (0.5–3.5), respectively (Figure). The estimated median time to return to FBF was generally stable over repeated intermittent use of MDZ-NS (1–45 SCEs assessed). 30% of patients were estimated to return to FBF within 30 min and almost 50% within 1 h in both SCEs treated with 1 and 2 MDZ-NS doses. The estimated proportion of patients returning to FBF within 2, 4, and 6 h of MDZ-NS administration was higher in SCEs treated with 1 versus 2 MDZ-NS doses. Over the course of repeated intermittent use of MDZ-NS, the estimated proportion of patients returning to FBF within 2 h of MDZ-NS administration increased by number of SCEs treated.

Conclusions: In this post hoc analysis, most patients returned to FBF within 24 h of repeated intermittent administration of 1 or 2 MDZ-NS doses. The median time to return to FBF was similar in SCEs treated with one and two doses and generally stable over the course of repeated intermittent MDZ-NS use. 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 two and six h after administration of 1 MDZ-NS dose. These data further support the favorable profile of repeated intermittent use of MDZ-NS in patients with SCs in terms of time to return to FBF.

Funding: Please list any funding that was received in support of this abstract.: UCB Pharma-sponsored