Evaluating Tolerability Endpoints Relevant to Clinicians and Patients in a Long-Term, Phase 3, Open-Label Repeat-Dose Safety Study of Diazepam Nasal Spray in Patients with Seizure Clusters
Abstract number :
2.215
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1825578
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:43 AM
Authors :
R. Hogan, MD - Washington University in St. Louis; Dennis Dlugos, MD - Children's Hospital of Philadelphia; Daniel Tarquinio, DO - Center for Rare Neurological Diseases; 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.; Enrique Carrazana, MD - Neurelis, Inc.
Rationale: Diazepam nasal spray (Valtoco®) provides a rapid and noninvasive route of diazepam administration. It is US Food and Drug Administration approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years and has been shown to have a safety profile consistent with rectal diazepam across age groups evaluated. This analysis of final data from a long-term, phase 3 safety study of diazepam nasal spray follows up on a previously presented analysis from a phase 1 study to discuss adverse events relevant to clinicians and patients.
Methods: Individuals aged 6–65 years with a clinical diagnosis of epilepsy experiencing seizure clusters were eligible. Care partners and patients were trained to administer diazepam nasal spray age- and weight-based doses of 5, 10, 15, or 20 mg. A second dose could be administered 4‒12 hours later, if needed. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms. Other safety/tolerability outcomes included nasal assessments by a trained observer and olfactory changes on the NIH Toolbox Odor Identification Test.
Results: A total of 175 patients were enrolled, and 163 (54.6% female; mean age, 23.1 years) received ≥1 dose of diazepam nasal spray. Overall, TEAEs were reported for 134 (82.2%) patients; 1 patient had a TEAE (0.6%) resulting in discontinuation that was not treatment related. There were 50 (30.7%) patients with serious TEAEs, none of which were treatment related; one serious TEAE resulted in death. TEAEs considered treatment related were reported in 30 (18.4%) patients; those in >2% of patients were nasal discomfort (6.1%) and headache (2.5%), which were mild or moderate. Rates of cardiorespiratory TEAEs were low (< 5% of patients). There were no reported TEAEs of respiratory depression, cardiac depression, or hypotension. Somnolence was reported in 11 (6.7%) patients and sedation in 2 (1.2%) patients. There were no clinically significant abnormalities noted for vital signs; specifically, there were no changes in respiratory rate, blood pressure, or pulse rate with diazepam nasal spray administration. Nasal irritation was uncommon, mild, and transient (Table 1). The few observations of mucosal edema, crusting, erythema, epistaxis, and nasal discharge were typically mild and similar to baseline. Odor identification results showed no clinically relevant olfactory changes in both age groups of interest (6–11 and ≥12 years) (Table 2).
Conclusions: In these final data from a long-term study, diazepam nasal spray as rescue therapy for seizure clusters did not result in any new safety signals. Adverse events of specific relevance to clinicians and patients such as somnolence, nasal tolerability, and olfactory changes were infrequent and minimal in severity in patients aged 6–65 years. Additionally, no changes in respiratory rate, blood pressure, and heart rate were observed. These final data confirm those from previous analyses.
Funding: Please list any funding that was received in support of this abstract.: Neurelis, Inc.
Anti-seizure Medications