SEIzure InterVAL (SEIVAL) Between Seizure Clusters and Quality of Life Across Time From a Phase 3 Safety Study of Diazepam Nasal Spray for Seizure Clusters
Sunita Misra1, Michael Sperling2, Vikram Rao3, Jurriaan Peters4, Enrique Carrazana5, Adrian Rabinowicz1
1Neurelis, Inc., San Diego, CA, 2Thomas Jefferson University, Philadelphia, PA, 3University of California, San Francisco, San Francisco, CA, 4Boston Children’s Hospital, Boston, MA, 5Neurelis, Inc., San Diego, CA and John A. Burns School of Medicine, University of Hawaii, Honolulu, HI
To examine duration between seizure clusters (SEIVAL) and quality of life in patients receiving diazepam nasal spray (Valtoco®) rescue therapy.
The long-term effect of intermittent rescue therapy on SEIVAL and potential interaction with quality of life (QoL) is unclear. We examined SEIVAL and QoL across time in a phase 3 safety study of diazepam nasal spray. Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years.
Patients (aged 6‒65 years) 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/period in each of 4 periods. The Quality of Life in Epilepsy (QOLIE)-31-P survey was used to measure QoL in adult patients (aged ≥18 years).
 Of 163 treated patients, 76 had ≥1 SEIVAL in each of 4 consecutive periods (consistent cohort) of whom 35 also had QOLIE-31-P data at baseline and day 365. In the full consistent cohort, mean SEIVAL increased by 12.9 days (P≤0.001) from Periods 1 to 4, while a similar increase in SEIVAL (12.2 days; P=0.022) was noted in the subgroup with QOLIE-31-P data. Overall, 71 treated adults completed the QOLIE-31-P at baseline, while 53 completed it at day 365. Changes in QOLIE-31-P scores were similar for all patients with QOLIE-31-P data (from 64.0 to 63.9) and for those in the consistent cohort (58.4 to 60.4). Seizure Worry and Social Functioning scores clinically improved for all patients (46.3 to 55.0, 52.9 to 61.0; respectively).
In the safety study of diazepam nasal spray, no change in overall QOLIE-31-P scores was observed. However, key QoL domains of Seizure Worry and Social Functioning improved over time, which paralleled increases in SEIVAL. These results will support future studies of factors that may affect QoL in patients using diazepam nasal spray.