Safety of Diazepam Nasal Spray in Patients with Rett Syndrome or Lennox-gastaut Syndrome: Subgroup Results from a Phase 3, Open-label, Repeat-dose Safety Study
Abstract number :
3.289
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2022
Submission ID :
2204003
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:22 AM
Authors :
Daniel Tarquinio, DO – Center for Rare Neurological Diseases; James Wheless, MD – Le Bonheur Children’s Hospital, University of Tennessee Health Science Center; Eric Segal, MD – Hackensack University Medical Center and Northeast Regional Epilepsy Group; Sunita Misra, MD, PhD – Neurelis, Inc.; Adrian Rabinowicz, MD – Neurelis, Inc.; Enrique Carrazana, MD – Neurelis, Inc.; University of Hawaii John A. Burns School of Medicine
Rationale: Seizure clusters are seizure emergencies associated with an increased risk of prolonged seizures and status epilepticus, more frequent emergency room visits, and disruption of daily life. Diazepam nasal spray (Valtoco®) is approved for acute treatment of seizure clusters in patients with epilepsy age ≥6 years. This study included a large cohort of patients with Rett syndrome, a rare X-linked disorder caused by mutations in the MCEP2 gene that occurs in ~1:10,000 female births. This analysis evaluates the safety of long-term treatment with diazepam nasal spray for seizure clusters in pediatric patients with Rett syndrome or Lennox-Gastaut syndrome (LGS) from a long-term safety study of diazepam nasal spray.
Methods: This was a phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray in patients with epilepsy. The study enrolled patients aged 6 to 65 years with frequent seizure clusters. Age- and weight-based doses of diazepam nasal spray were administered and second doses were administered 4 to 12 hours later if needed. The investigator could adjust dosing for safety or effectiveness. Treatment-emergent adverse events (TEAEs) were recorded along with other safety assessments. Use of second doses within 24 hours of the first was used as a proxy for effectiveness. Patients with Rett syndrome and LGS were identified based on patients’ medical histories.
Results: Of 163 treated patients in the safety population, 78 (47.9%) were aged 6 to 17 years. A total of 16 (20.5%) pediatric patients had a diagnosis of Rett syndrome; 9 patients (7 pediatric, 2 adults) were diagnosed with LGS, 1 patient was diagnosed with Rett syndrome and also LGS (Table). Second doses were infrequent, used in 18.4% of seizure clusters in the Rett syndrome subgroup and 4.1% of the LGS group. A second dose was used in 12.6% of clusters in the overall study safety population. Retention rate to study closure was 81.3% in the Rett syndrome subgroup and 77.8% in the LGS group. Overall, TEAE rates in children with Rett syndrome (87.5%) were similar to the LGS group (66.7%). Treatment-related TEAEs occurred in 3 (18.8%) patients with Rett syndrome and 1 (11.1%) with LGS. No treatment-related TEAEs occurred in >1 patient in either group. There were no cases of cardiorespiratory depression or treatment-related serious TEAEs. There were no discontinuations due to TEAEs and no deaths in either group.
Conclusions: In this analysis of patients with Rett syndrome or LGS from the long-term, safety study of diazepam nasal spray, the low percentage of seizure clusters requiring a second dose was similar to the overall study findings, which suggests initial-dose effectiveness in these highly intractable subgroups. There were no new safety signals compared with previous diazepam formulations, and the retention rate was high.
Funding: Neurelis, Inc.
Anti-seizure Medications