Examination of Interval Between Seizure Clusters Across Time for Pediatric and Adult Patient Subgroups in a Long-term, Open-label Safety Study of Diazepam Nasal Spray
Abstract number :
3.285
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2022
Submission ID :
2203998
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:22 AM
Authors :
Jurriaan Peters, MD, PhD – Harvard Medical School and Boston Children’s Hospital, Boston, MA; Sunita Misra, MD, PhD – Neurelis, Inc.; Michael Sperling, MD – Thomas Jefferson University; Vikram Rao, MD, PhD – University of California; Charles Davis, PhD – SD Biostatistics, Inc; Enrique Carrazana, MD – Neurelis, Inc.; University of Hawaii John A. Burns School of Medicine; Adrian Rabinowicz, MD – Neurelis, Inc.
Rationale: Metrics for the effectiveness of rescue therapies for seizure clusters across multiday time periods have not been established. This post hoc analysis explores SEIzure cluster interVAL (SEIVAL; time between seizure clusters) in patients with epilepsy and seizure clusters from a long-term safety study of diazepam nasal spray (Valtoco®). SEIVAL can be applied as a novel measure of effectiveness for intermittent rescue therapy. Included here are observations on pediatric and adult patient subgroup SEIVAL changes with diazepam nasal spray treatment across time. Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy age ≥6 years.
Methods: This was a long-term, open-label, repeat-dose safety study of diazepam nasal spray in patients with epilepsy. The study enrolled patients aged 6–65 years with frequent seizure clusters. Age- and weight-based doses of diazepam nasal spray were administered. Patients and care partners were instructed to administer second doses 4–12 hours after the initial dose if needed. SEIVAL was evaluated across 4 consecutive 90-day periods (total 360 days) for pediatric (6–17 years) and adult (≥18 years) patient subgroups. Paired t tests assessed statistical significance. A consistent cohort of patients who had data in each of periods 1, 2, 3, and 4 was used to reduce potential confounding with a variable cohort. Second doses within 24 hours of the first were excluded to eliminate retreatments for the same seizure cluster.
Results: A total of 175 patients were enrolled in the study; 163 patients received ≥1 dose of diazepam nasal spray. Seventy-six of these patients had ≥1 SEIVAL in each of the 4 periods and were included in the consistent cohort. For the overall (all-age) group, mean SEIVALs increased significantly from 13.9 days (Period 1) to 26.8 days (Period 4) (P< 0.001). The pediatric and adult subgroups showed similar patterns of increases in SEIVALs from Period 1 to 4 compared with the overall age group across these periods. In the pediatric subgroup (n=32), mean SEIVAL for Period 1 was 13.0, rising to 25.9 for Period 4 (P=0.02). In the adult subgroup (n=44), mean SEIVAL for Period 1 was 14.6, rising to 27.5 for Period 4 (P=0.01).
Anti-seizure Medications