Assessment of Study Endpoints for Patients Discontinuing from a Phase 3, Long-Term, Open-Label, Repeat-Dose, Safety Study of Diazepam Nasal Spray for Acute Treatment of Seizure Clusters
Abstract number :
2.21
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1825616
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Enrique Carrazana, MD - Neurelis, Inc.; Daniel Tarquinio, DO - Center for Rare Neurological Diseases; R. Edward Hogan, MD - Washington University in St. Louis; Michael Sperling, MD - Thomas Jefferson University; James Wheless, MD - Le Bonheur Children’s Hospital, University of Tennessee Health Science Center; Jay Desai, MD - Children’s Hospital of Los Angeles; Kore Liow, MD - Hawaii Pacific Neuroscience; Gregory Cascino, MD - Mayo Clinic; Adrian Rabinowicz, MD - Neurelis, Inc.
Rationale: Patients with severe and poorly controlled epilepsy are more likely to have seizure clusters, which are associated with increased risk for status epilepticus and death. 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 evaluated patients from a phase 3, long-term, open-label, repeat-dose, safety study of diazepam nasal spray to compare results for those who completed the study with those who discontinued.
Methods: Eligible patients with epilepsy were aged 6–65 years and experienced seizure clusters. Patients and care partners were trained to administer age- and weight-based doses of 5, 10, 15, or 20 mg of diazepam nasal spray, with a second dose 4–12 hours later if needed. Proportion of seizures for which second doses were used was a proxy measure for effectiveness. Safety assessments included treatment-emergent adverse events (TEAEs) and treatment-related TEAEs. The safety population included patients who received ≥1 dose of diazepam nasal spray.
Results: Of 175 patients enrolled, 163 were included in the safety population and had a total of 3853 seizure clusters, which were treated with a total of 4390 doses of diazepam nasal spray. Overall mean duration on the study was 17.4 months (range: 1.8–40.5 months). Of the 163 patients, 117 (71.8%) completed the study, and 46 (28.2%) discontinued prematurely. The most common reasons for discontinuation ( >15%) were withdrawal by patient (41.3% [19/46]), lost to follow-up (23.9% [11/46]), and study closure (15.2% [7/46]) (Figure).
The mean age of the groups that completed or discontinued was similar at 23.6 years and 21.9 years, respectively. Duration of exposure was ≥12 months for 113 (96.6%) completers and 20 (43.5%) of those who discontinued. Mean doses per month was 2.3 for both groups. Proportion of second doses was similar at 12.6% (401 of 3195 seizure clusters) for completers and 12.8% (84 of 658 seizure clusters) for those who discontinued. TEAEs were reported for 104 (88.9%) completers, including 39 (33.3%) with serious TEAEs and 22 (18.8%) with treatment-related TEAEs (Table). Among those who discontinued, the proportions of TEAEs were consistently lower: TEAEs were reported for 30 (65.2%), including 11 (23.9%) with serious TEAEs and 8 (17.4%) with treatment-related TEAEs. Among the discontinuations, one was due to an adverse event of major depression and one to sudden unexpected death in epilepsy; neither of these was considered to be treatment related.
Conclusions: These results from a long-term safety study demonstrate similarities in safety and effectiveness of diazepam nasal spray between completers and those who discontinued. Only one discontinuation was due to a TEAE and one to death, neither of which were deemed treatment related. These results suggest that safety and effectiveness of diazepam nasal spray had minimal effect on discontinuations.
Funding: Please list any funding that was received in support of this abstract.: Neurelis, Inc.
Anti-seizure Medications