Syndi Seinfeld1, Michael A Gelfand2, Allen H Heller3, Carla Buan4, Gary Slatko4. 1. Joe DiMaggio Children's Hospital, Hollywood, FL, USA. 2. University of Pennsylvania, Philadelphia, PA, USA. 3. Pharma Study Design, Woodbridge, CT, USA. 4. Aquestive Therapeutics, Inc., Warren, NJ, USA.
Abstract
OBJECTIVE: Diazepam buccal film (DBF) is in development for treatment of patients experiencing bouts of increased seizure activity. We assessed safety, tolerability, and usability of self- or caregiver-administered DBF in the outpatient setting. METHODS: Patients aged 2-65 years needing treatment with a rescue benzodiazepine at least once monthly were eligible for the study. DBF (5-17.5 mg) was dispensed based on age and body weight. Patients/caregivers administered DBF for up to five seizure episodes per month. Adverse events (AEs) and usability assessments were recorded after the first dose, then every 3 months. RESULTS: Onehundred eighteen patients who used ≥1 DBF dose (adults, n = 82; adolescents, n = 19; children, n = 17) were enrolled. Eleven treatment-related AEs (10 being mild or moderate in severity) occurred in nine (7.6%) patients over a mean of 243 days of follow-up. No patient discontinued participation because of AEs. Mild local buccal discomfort, buccal swelling, and cheek skin sensitivity were reported by one patient each. Twenty-two serious AEs were reported; one was treatment-related. The three deaths reported, all unrelated to DBF, resulted from seizures or seizure with brain malignancy. Self-administration by adults was attempted on 23.6% (188/795) of use occasions. Administration of DBF occurred under ictal or peri-ictal conditions on 49.5% (538/1087) of use occasions, and DBF was successfully administered on a first or second attempt on 96.6% (1050/1087) of use occasions. Overall, patients received their dose of DBF on 99.2% (1078/1087) of use occasions. A second DBF dose was required within 24 hours after the first dose on 8.5% (92/1087) of use occasions. SIGNIFICANCE: In this observational study of chronic intermittent use, DBF was easy to administer, safe, and well tolerated in adult, adolescent, and pediatric patients with epilepsy experiencing seizure emergencies. DBF can be readily self-administered by adults with epilepsy, as well as successfully administered by a caregiver in seizure emergencies.
OBJECTIVE:Diazepam buccal film (DBF) is in development for treatment of patients experiencing bouts of increased seizure activity. We assessed safety, tolerability, and usability of self- or caregiver-administered DBF in the outpatient setting. METHODS:Patients aged 2-65 years needing treatment with a rescue benzodiazepine at least once monthly were eligible for the study. DBF (5-17.5 mg) was dispensed based on age and body weight. Patients/caregivers administered DBF for up to five seizure episodes per month. Adverse events (AEs) and usability assessments were recorded after the first dose, then every 3 months. RESULTS: Onehundred eighteen patients who used ≥1 DBF dose (adults, n = 82; adolescents, n = 19; children, n = 17) were enrolled. Eleven treatment-related AEs (10 being mild or moderate in severity) occurred in nine (7.6%) patients over a mean of 243 days of follow-up. No patient discontinued participation because of AEs. Mild local buccal discomfort, buccal swelling, and cheek skin sensitivity were reported by one patient each. Twenty-two serious AEs were reported; one was treatment-related. The three deaths reported, all unrelated to DBF, resulted from seizures or seizure with brain malignancy. Self-administration by adults was attempted on 23.6% (188/795) of use occasions. Administration of DBF occurred under ictal or peri-ictal conditions on 49.5% (538/1087) of use occasions, and DBF was successfully administered on a first or second attempt on 96.6% (1050/1087) of use occasions. Overall, patients received their dose of DBF on 99.2% (1078/1087) of use occasions. A second DBF dose was required within 24 hours after the first dose on 8.5% (92/1087) of use occasions. SIGNIFICANCE: In this observational study of chronic intermittent use, DBF was easy to administer, safe, and well tolerated in adult, adolescent, and pediatric patients with epilepsy experiencing seizure emergencies. DBF can be readily self-administered by adults with epilepsy, as well as successfully administered by a caregiver in seizure emergencies.