Tolerability of Midazolam Nasal Spray in Pediatric Subjects with Epilepsy (P6.235)

Objective: An objective of this study was to characterize safety and tolerability of midazolam (MDZ) nasal spray (USL261) in pediatric subjects with epilepsy to inform its potential use in this population. Background: USL261 is in development as rescue treatment for individuals with intermittent bouts of increased seizure activity. Design/Methods: This open-label, phase 1 study evaluated single doses of USL261. Subjects (2–13 years) with focal or generalized epilepsy received 5.0, 2.5, or 1.25 mg USL261 based on body weight (≥40–≤60, ≥20– Results: All 36 enrolled individuals (n=12/cohort) completed the study and were included in the safety analysis. Aside from expected age, weight, and BMI differences, demographic and baseline characteristics were generally similar across the three cohorts. Twenty-five subjects (69.4%) had ≥1 TEAE, with similar TEAE incidence across cohorts (58.3%, 75.0%, and 75.0% in the 5.0, 2.5, and 1.25 mg cohorts, respectively). Of 58 reported TEAEs, 82.8% were considered mild and 77.6% were categorized as related to study drug. Most common TEAEs (n, % of subjects) were somnolence (21, 58.3%), product taste abnormal (4, 11.1%), and nasal discomfort (3, 8.3%). No treatment-related serious adverse events were reported. Changes in vital signs and clinical laboratory results revealed no overall patterns of clinical concern. No subjects had any suicidal ideation or behavior at any time point during the study. There were no clinically significant abnormal nasal exam results. Physical and neurological examination results were similar between screening and follow-up. Conclusions: USL261—MDZ nasal spray—was generally well tolerated with no clinically meaningful safety concerns. These safety and tolerability results support the continued development of USL261 in pediatric patients with epilepsy. Study Supported by: Upsher-Smith Laboratories, Inc. Disclosure: Dr. Bancke has received person compensation for activities with Upsher-Smith Laboratories, Inc. as an employee. Dr. Meng has received personal compensation for activities with Upsher-Smith Laboratories, Inc. as an employee. Dr. Kapelan has received personal compensation for activities with Upsher-Smith Laboratories, Inc. as an employee. Dr. Moe has receievd personal compensation for activities with Upsher-Smith Laboratories, Inc. as an employee. Dr. Berg has received personal compensation for activities with Upsher-Smith Laboratories, Inc. as an employee. Dr. Van Ess has received personal compensation for activities with Upsher-Smith Laboratories Inc. as an employee.