Abstracts

Rationale: Diazepam buccal soluble film (DBSF) is a novel dosage form of diazepam under development for the management of selected patients with refractory epilepsy who require intermittent use of diazepam to control episodes of increased seizure activity. DBSF has the potential to be the first orally administered treatment for this indication and would provide an alternative to rectal diazepam gel. DBSF is administered by placing the film against the inner aspect of the cheek, where it adheres, dissolves and releases drug onto the buccal mucosa. The DBSF dosage form is expected to be accepted by a broad range of patients with epilepsy. A Phase 2 pharmacokinetic study in the epilepsy monitoring unit (EMU) assessed safety, pharmacokinetics and usability of DBSF. Here we present results on the usability of the product. Methods: This was a Phase 2, multi-center, open-label, crossover study in adult subjects who were studied during two treatment visits separated by approximately three weeks. The study enrolled male and female subjects 17-65 years of age with a clinical diagnosis of epilepsy (tonic clonic seizures or focal seizures with impaired awareness) who required EMU evaluation. Subjects received DBSF 12.5 mg during the interictal state (Treatment A) and the ictal/periictal state (during or within 5 min of a seizure; Treatment B). Usability endpoints for investigator placement of DBSF included: (1) whether successful placement was achieved, (2) number of attempts needed to successfully insert the film, (3) whether the subject spit or blew out the film, and (4) whether or not DBSF was swallowed. Results: A total of 35 subjects received at least one dose of DBSF.  Of these subjects, 33 subjects received Treatment A and 33 received Treatment B. During both Treatment A and Treatment B, there were no unsuccessful attempts of DBSF insertion. During Treatment A, 2 (6.1%) subjects, and during Treatment B, 1(3.0%) subject, swallowed DBSF during dosing. Three (9.1%) additional subjects swallowed DBSF per the protocol, which instructed all subjects to swallow the film if it had not completely dissolved 15 minutes after placement. During Treatment A, no patients spit or blew out DBSF following initial adherence to the buccal mucosa, while 3 (9.1%) subjects spit or blew out the film during Treatment B following initial placement. DBSF was generally safe and well tolerated.  The most common adverse event possibly related to drug was somnolence reported in two (5.7 %) of 35 of subjects. There were no serious adverse events related to study drug, and no subject withdrew because of an adverse event. Conclusions: In the EMU setting, DBSF was successfully placed and generally used correctly in both the interictal and ictal/periictal states. This study suggests that DBSF is a practical oral treatment for adults with refractory epilepsy who require intermittent use of diazepam to control episodes of increased seizure activity. Studies are currently in progress to evaluate usability in the home setting. Funding: This study was funded by Aquestive Therapeutics, Inc