Significant Improvements in SEIzure InterVAL (Time Between Seizure Clusters) Across Time Irrespective of Age or Change in Concomitant Treatments in a Long-Term, Open-Label Safety Study of Diazepam Nasal Spray
Michael Sperling1, Sunita Misra2, Vikram Rao3, Jurriaan Peters4, Enrique Carrazana5, Adrian Rabinowicz2
1Thomas Jefferson University, Philadelphia, PA, 2Neurelis, Inc., San Diego, CA, 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
Objective:
To characterize time between seizure clusters in patients using diazepam nasal spray (Valtoco®) intermittent rescue therapy.
Background:
Metrics for effectiveness of rescue therapies for seizure clusters across multiple days are lacking. We explored a novel measure of effectiveness, SEIzure interVAL (SEIVAL; time between seizure clusters) in a long-term safety study of diazepam nasal spray, which is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years.
Design/Methods:
A post hoc analysis of a long-term, open-label, repeat-dose safety study of diazepam nasal spray in patients aged 6–65 years with epilepsy and frequent seizure clusters evaluated SEIVAL across 4 consecutive 90-day periods (total 360 days). Paired t tests assessed statistical significance.
Results:
Of 175 enrolled patients, 163 received ≥1 dose of diazepam nasal spray, and 120 had SEIVAL data in period 1 and another period. A consistent cohort (n=76) had data in all 4 periods. In the 120 patients, mean SEIVAL increased from 14.8 to 35.8 days (Period 1 to 4). In the consistent cohort, mean SEIVAL increased from 13.9 to 26.8 days (P≤0.001). In pediatric patients (age 6–17 years, n=32), mean SEIVAL increased from 13.0 to 25.9 days (P=0.02). In adults (n=44), mean SEIVAL increased from 14.6 to 27.5 days (P=0.01). Mean SEIVAL also increased in patients with (n=56; from 13.9–25.8 days) and without (n=20; from 14.1–29.6 days) changes in concomitant antiseizure drug (ASD) therapy during the study.
Conclusions:
Across 12 months, a statistically significant change in SEIVAL was observed, which may reflect a beneficial effect of intermittent rescue therapy with diazepam nasal spray and appears to be independent of age or concomitant ASDs. These findings may reflect patient behavior or other factors, including a change in the underlying biology of seizure clusters; these hypotheses warrant further study.