Abstracts

Seizure Cluster Interval (SEIVAL) Between Seizure Clusters and Quality of Life Across Time from a Phase 3 Safety Study of Diazepam Nasal Spray for Seizure Clusters

Abstract number : 3.286
Submission category : 7. Anti-seizure Medications / 7B. Clinical Trials
Year : 2022
Submission ID : 2203999
Source : www.aesnet.org
Presentation date : 12/5/2022 12:00:00 PM
Published date : Nov 22, 2022, 05:22 AM

Authors :
Sunita Misra, MD, PhD – Neurelis, Inc.; Michael Sperling, MD – Thomas Jefferson University; Vikram Rao, MD, PhD – University of California; Jurriaan Peters, MD, PhD – Boston Children's Hospital; Charles Davis, PhD – SD Biostatistics, Inc; Enrique Carrazana, MD, PhD – Neurelis, Inc.; University of Hawaii John A. Burns School of Medicine; Adrian Rabinowicz, MD – Neurelis, Inc.

Rationale: Timing between seizures has been used to evaluate daily antiseizure drugs but not intermittent rescue therapy. The long-term effect of intermittent rescue therapy on the duration between seizure clusters (SEIVAL) and potential interaction with quality of life (QoL) is unclear. Here, we examined SEIVAL and QoL across time in a phase 3 safety study of diazepam nasal spray (Valtoco®). Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years.

Methods: Patients (aged 6‒65 years) in a long-term, open-label safety study received age- and weight-based doses of diazepam nasal spray for seizure clusters. SEIVAL was assessed using 90-day periods in patients treated with ≥2 doses per period in each of 4 periods (360 days). This consistent cohort across time was selected to help control for survival bias. Second doses administered within 24 hours of the first (ie, retreatments) were not included. In a separate analysis, the Quality of Life in Epilepsy (QOLIE)-31-P survey was used to measure QoL in adults using a weighted composite of 7 subscales. Higher scores (100-point scales) indicate better QoL. The QOLIE-31-P was completed at baseline (day 0) and days 30, 150, 270, and 365 by patients aged ≥18 years. It was hypothesized that Seizure Worry and Social Functioning subscales would be most relevant to rescue therapy. SEIVAL and QOLIE-31-P were compared.

Results::Of 175 enrolled patients, 163 were treated with ≥1 dose of diazepam nasal spray. In the SEIVAL analysis of pediatric and adult patients, 151 had data, and 76 had ≥1 SEIVAL in each of 4 consecutive periods (consistent cohort). Within the consistent cohort, 35 adults completed the QOLIE-31-P at baseline and day 365. In the full 76-patient consistent cohort, mean SEIVAL increased by 12.9 days (P < 0.001) from Periods 1 to 4, while a similar increase was noted in SEIVAL (12.2 days; P=0.022) in the subgroup of 35 adults with QOLIE-31-P data. In the QOLIE-31-P analysis (Figure
Anti-seizure Medications