Abstracts

Comparison of Safety and Effectiveness of Diazepam Nasal Spray in Male and Female Patients: Post Hoc Analysis of Data from a Phase 3 Safety Study

Abstract number : 2.264
Submission category : 7. Anti-seizure Medications / 7B. Clinical Trials
Year : 2023
Submission ID : 591
Source : www.aesnet.org
Presentation date : 12/3/2023 12:00:00 AM
Published date :

Authors :
Presenting Author: James Wheless, MD – Le Bonheur Children's Hospital

Robert Hogan, MD – Washington University in St. Louis, St. Louis, MO; Charles Davis, PhD – CSD Biostatistics, Oro Valley, AZ; Sunita Misra, MD, PhD – Neurelis, Inc., San Diego, CA; Enrique Carrazana, MD – Neurelis, Inc., San Diego, CA; University of Hawaii John A. Burns School of Medicine, Honolulu, HI; Adrian Rabinowicz, MD – Neurelis, Inc., San Diego, CA

Rationale:
Sex differences in drug metabolism have been described, which include differences in expression of key cytochrome P450 enzymes important for benzodiazepine metabolism. The influence of sex on outcomes associated with the intranasal route of administration is unclear. A post hoc analysis was conducted to evaluate the safety and effectiveness of diazepam nasal spray, including the duration in days between seizure clusters (SEIzure cluster interVAL [SEIVAL]) over time, in male and female patients who participated in the phase 3 open-label safety study of diazepam nasal spray. Diazepam nasal spray (Valtoco®) is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥ 6 years.

Methods:
Patients (aged 6–65 y) in a phase 3, long-term, open-label safety study of diazepam nasal spray received 5, 10, 15, or 20mg doses (based on age and weight) to treat seizure clusters. Second doses could be administered four to twelve hours later if needed. Rates of treatment-emergent adverse events (TEAEs), serious TEAEs, and treatment-related TEAEs were recorded. The number of second doses given within 24 hours of the first was used as a proxy for effectiveness. SEIVAL was determined using 90-day periods for patients treated with two doses per period across four periods (360 d). Second doses administered within 24 hours of the first dose were excluded from the analysis to eliminate re-treatments (ie, second doses) for the same seizure cluster.

Results:
Of 175 patients enrolled in the study, 163 were treated with 1 dose of diazepam nasal spray. Demographic characteristics, frequency of use, and the safety profile of diazepam nasal spray were generally similar between male (n=74, 45.4%) and female (n=89, 54.6%) patients (Table), and ~16% of both sexes self-administered the nasal spray. In male patients, 144 of 1537 seizure clusters (9.4%) received a second dose of diazepam nasal spray; in female patients, 341 of 2316 seizure clusters (14.7%) received a second dose.

A total of 76 patients had ≥ 1 SEIVAL in each of the four periods. In male patients, mean SEIVAL increased from 16.3 days in Period one to 26.8 days in Period four (P< 0.05). Female patients had a slightly larger increase in mean SEIVAL from Period 1 (12.3 d) to Period 4 (26.8 d) (P< 0.01).
Anti-seizure Medications