Authors :
Presenting Author: Joyce Cramer, BS – Consultant, Yale University School of Medicine
Eric Segal, MD – Hackensack University Medical Center and Northeast Regional Epilepsy Group and Hackensack Meridian School of Medicine
James Wheless, BScPharm, MD, FAAP, FACP, FAAN, FAES, FCNS – University of Tennessee Health Science Center and Le Bonheur Children's Hospital
Jurriaan Peters, MD PhD – Boston Children's Hospital
Steven M Wolf, MD – Westchester Medical Center, Hawthorne, NY, United States
Miguel Lopez-Toledano, PhD – Neurelis, Inc.
Leock Ngo, PhD – Neurelis, Inc.
Enrique Carrazana, MD – Neurelis, Inc., John A. Burns School of Medicine; University of Hawaii, Honolulu, HI
Adrian Rabinowicz, MD – Neurelis, Inc., Center for Molecular Biology and Biotechnology (CMBB) in the Charles E. Schmidt Collage of Science at Florida Atlantic University
Rationale:
Most seizure clusters occur outside hospitals, so treatments should be simple for caregivers to use quickly in community settings to avoid negative outcomes. Two diazepam formulations are approved by the US Food and Drug Administration for the treatment of SCs in patients with epilepsy aged ≥2 y: diazepam rectal gel and diazepam nasal spray. Compared with rectal administration, the nasal route allows for easier access, is noninvasive, and is more socially acceptable. Use of diazepam nasal spray in children aged 2-5 y was evaluated in a Phase 1/2 pharmacokinetics (PK) and safety study, which included a seizure severity questionnaire (SSQ) and a caregiver questionnaire completed at study visits.Methods:
Children aged 2-5 y with focal or generalized epilepsy with motor seizures or seizures with clear alteration of awareness were enrolled in an open-label PK study of diazepam nasal spray with a 180-day open-label safety period and an optional extension period. During the safety and optional periods, diazepam nasal spray was administered by caregivers as needed for acute repetitive seizures or frequent seizures. The diazepam nasal spray dose (5, 10, or 15 mg) was based on the patient’s age and weight (0.5 mg/kg). A seizure severity questionnaire and a caregiver assessment with questions covering the past 4 weeks were completed at baseline and at follow-up visits (Days 30, 90, and 180) during the safety period. This preliminary analysis examines responses for a subset of questions, selected a priori as relevant to intermittent treatment.Results:
Of the 36 patients (mean age: 3.9 y, range: 2.0-5.8 y) who were treated and included in the safety period, 31 patients completed the safety period, and 27 patients completed the optional extension period. A total of 471 doses of diazepam nasal spray were administered (mean [SD] duration of exposure, 15.45 [8.43] months). At the end of the safety period (Day 180), more caregivers (13/20) responded on the SSQ that it did not take a while for patients to recover after seizures. The majority of those 7 patients who reported it took a while to recover had cognitive (6), emotional (4), and physical (7) effects after seizures (Figure 1). For the caregiver questionnaire (Figure 2) at Day 180, responses were substantially more positive than or remained stable with baseline: most said that SCs affected other responsibilities not at all or rarely (63%), SCs caused little or no family stress (70%), recovery improved very much or a lot (69%), and SCs were much or a little milder and fewer since starting treatment (67%).
Conclusions:
At the end of the 180-day period, caregivers reported that most patients recovered quickly and that SCs did not affect other responsibilities, were not stressful to the family, and were milder and fewer and that recovery improved with treatment. These insights into caregiver perceptions reinforce the value of appropriate SC management. Funding: Neurelis, Inc.