Abstract Details

Title Pharmacokinetics of Diazepam Buccal Film in Adult Patients with Epilepsy: Comparison with Diazepam Rectal Gel

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S25 - Epilepsy/Clinical Neurophysiology (EEG) 2 (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

Objective To assess the pharmacokinetics (PK) of diazepam buccal film (DBF) in adults with epilepsy (weight-based regimen; 12.5–17.5 mg) versus diazepam rectal gel (DRG; FDA-approved weight-based regimen; 12.5–20 mg).

Background DBF is a novel form of diazepam under development for patients with refractory epilepsy requiring intermittent diazepam to control increased seizure activity.

Design/Methods Adults aged 18–65 years with epilepsy on a stable regimen of ≥1 antiseizure drug were enrolled in a 2-period crossover study (NCT03953820) to receive a single dose of DBF or DRG separated by a 28-day washout. Diazepam plasma samples were obtained pre-dose and at intervals until 10 days post-dose for analysis of maximal plasma concentration (C_max), time to C_max (T_max), area under the curve (AUC) to the last measurable concentration, and AUC extrapolated to infinity. Adverse events (AEs) were monitored.

Results

PK profiles valid for DBF and DRG analysis were available for 28 of 31 enrolled subjects (15 females; mean±SD weight 84.6±20.6 kg). Subjects were excluded if both treatments were not completed (n=2), or if pre-dose diazepam concentrations were >5% of C_max (n=1). Diazepam mean±SD dose was 15.4±1.9 mg and 17.1±3.0 mg for DBF and DRG, respectively. For the overall population, DBF and DRG geometric mean C_max values were 204.26 ng/mL (geometric SD [GSD] 136.12–306.49) and 211.22 ng/mL (GSD 87.71–508.63), respectively, indicating that C_max values following DBF were comparable but significantly less variable than values following DRG (P<0.0001). AUC values were higher for DBF versus DRG, and median T_max for DBF and DRG was 1.0 and 0.52 hours, respectively (P<0.05). Three of 28 subjects following DRG dosing failed to achieve plasma concentration ≥70 ng/mL. There were no drug-related serious AEs.

Conclusions A single DBF dose administered to adults with epilepsy provides diazepam exposure diazepam similar to DRG with significantly less variability.

Authors/Disclosures
Michael A. Rogawski, MD, PhD (University of California - Davis) PRESENTER	Dr. Rogawski has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Xenon Pharmaceuticals.
Allen H H. Heller, MD, MPH (Pharma Study Design LLC)	Dr. Heller has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for Epalex Corporation. Dr. Heller has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Aquestive Therapeutics Inc.. Dr. Heller has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celanese Corporation. Dr. Heller has stock in Epalex Corporation.
Simon J. Farrow, MD, BM, Bch	No disclosure on file
	No disclosure on file
Pavel Klein, MD, FAAN (Mid-atlantic Epilepsy and Sleep Center)	The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Aquestive. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurelis. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB Pharma. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for SK Life Sience. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alliance. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvelle Therapeutics. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Aquestive. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Eisai. Dr. Klein has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for UCB Pharma. Dr. Klein has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for SK Life Sciences. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sunovion. Dr. Klein has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for PrevEp. Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Fenwick . Dr. Klein has received research support from DOD/CURE.
	No disclosure on file
Gary Slatko, MD (Aquestive Therapeutics)	Dr. Slatko has received personal compensation for serving as an employee of Aquestive Therapeutics. Dr. Slatko has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Aquestive Therapeutics.

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