Safety and Time to Second Doses in Age Subgroups of Patients with Seizure Clusters Treated with Diazepam Nasal Spray in a Phase 3, Open-Label, Repeat-Dose Safety Study
Abstract number :
3.274
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1825543
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
James Wheless, MD - University of Tennessee Health Science Center & Le Bonheur Children’s Hospital; R. Edward Hogan, MD - University of Tennessee Health Science Center; Michael Sperling, MD - Thomas Jefferson University; Kore Liow, MD - Hawaii Pacific Neuroscience; Daniel Tarquinio, DO - Center for Rare Neurological Diseases; Jay Desai, MD - Children’s Hospital of Los Angeles; Dennis Dlugos, MD - Children's Hospital of Philadelphia; Gregory Cascino, MD - Mayo Clinic; Enrique Carrazana, MD - Neurelis, Inc.; Adrian Rabinowicz, MD - Neurelis, Inc.
Rationale: Nonintraveous benzodiazepines are the key rescue therapies for treatment of outpatient seizure clusters in patients with epilepsy. Diazepam nasal spray is approved by the US Food and Drug Administration for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. This analysis assessed safety and time to second doses (a proxy for effectiveness) in patients with epilepsy aged 6–11 years and 12–65 years from the long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray.
Methods: The study enrolled patients aged 6–65 years with frequent seizure clusters. Patients and care partners were trained to administer doses of 5, 10, 15, or 20 mg of diazepam nasal spray based on age (≤11 or ≥12 years) and weight, with instructions to administer second doses 4–12 hours later if needed. Investigators could adjust doses for effectiveness or safety reasons. Seizures, drug administration, and treatment-emergent adverse events (TEAEs) were recorded in seizure diaries. Use of second doses at 4, 6, 12, and 24 hours was assessed for patients aged 6–11 and ≥12 years.
Results: The study enrolled 175 patients, with 163 treated and included in the safety population. Mean age was 23.1 years (6–11 years, n=45 [27.6%]; 12–65 years, n=118 [72.4%]). Overall mean duration of exposure was 17.4 months and was ≥12 months in 35 (77.8%) of the 6–11 group and 98 (83.1%) of the ≥12 group. The 6–11 group had 784 total seizure clusters, with second doses used in 22 clusters within 4 hours, 7 in 4–6 hours, 22 in 6–12 hours, and 39 in 12–24 hours, for a total of 90 (11.5%) second doses (Figure). The ≥12 group had 3069 total seizure clusters, with second doses used in 130 clusters within 4 hours, 65 in 4–6 hours, 234 in 6–12 hours, and 105 in 12–24 hours, for a total of 395 (12.9%) second doses.
TEAEs were reported in 91.1% of patients in the 6–11 group, including 40.0% with serious TEAEs and 6.7% with treatment-related TEAEs (Table). In the ≥12 group, TEAEs were reported for 78.8% of patients, including 27.1% with serious TEAEs and 22.9% with treatment-related TEAEs. None of the serious TEAEs in either group were considered treatment related. One patient in the ≥12 group discontinued owing to a TEAE, and one died; neither was deemed treatment related. The overall completion rate was 71.8%; 7 patients discontinued owing to study closure. Aside from discontinuations due to study closure, the retention rate was 75.5% for the 6–11 group and 76.3% for the ≥12 group.
Conclusions: In an analysis of age subgroups of patients with seizure clusters from a long-term safety study of diazepam nasal spray, use of second doses, safety, and retention rate were similar independent of subgroup. Second doses were administered within 24 hours for 11.5% of seizure clusters among patients 6–11 years and 12.9% among patients ≥12 years. The safety profiles were consistent with the established profile of rectal diazepam. The retention rate was ~76% in both subgroups.
Funding: Please list any funding that was received in support of this abstract.: Neurelis, Inc.
Anti-seizure Medications