Pharmacokinetics of Clobazam and N-desmethylclobazam Following Administration of Clobazam Oral Soluble Film
Abstract number :
3.295
Submission category :
7. Antiepileptic Drugs / 7B. Clinical Trials
Year :
2018
Submission ID :
507370
Source :
www.aesnet.org
Presentation date :
12/3/2018 1:55:12 PM
Published date :
Nov 5, 2018, 18:00 PM
Authors :
Allen H. Heller, Pharma Study Design LLC; Stephen Wargacki, Aquestive Therapeutics Inc; Cassie Jung, Aquestive Therapeutics Inc; David J. Wyatt, Syneos Health Inc; and A. Mark Schobel, Aquestive Therapeutics Inc
Rationale: Clobazam oral soluble film (COSF) is a novel dosage form under development for adjunctive treatment of seizures in Lennox-Gastaut syndrome (LGS). The film formulation has the potential to contribute to the care of patients with LGS by providing a means for easier and more reliable administration than the currently available clobazam formulations. We assessed the pharmacokinetics (PK) of clobazam and its active metabolite, N-desmethylclobazam, administered as single doses of COSF 20 and 10 mg (Aquestive Therapeutics) compared with clobazam tablets 20 and 10 mg (Lundbeck, US). Methods: Healthy adult volunteers (N=51) were enrolled in a single-dose, open-label, randomized four-sequence, four-period, crossover: (A) COSF 20 mg; (B) clobazam tablet 20 mg; (C) COSF 10 mg; and (D) clobazam tablet 10 mg. PK sampling for both clobazam and N-desmethylclobazam was carried out until 21 days post-dose with a 28-day washout. Subjects were monitored for adverse events (AE) throughout the study. Results: COSF at single doses of 10 and 20 mg was bioequivalent to the clobazam tablet at both doses for both clobazam and for N-desmethylclobazam. The time until maximal plasma concentration (Tmax) for clobazam was similar for COSF and the tablet (1.5 to 2 hours at both dose levels). The PK for parent drug and active metabolite were demonstrated to be dose-proportional. Adverse events were as expected for clobazam, and dose-related across the treatment groups, with somnolence the most common. Most events were mild and none serious or severe. Conclusions: COSF is a novel clobazam dosage form that is bioequivalent to the clobazam tablet with respect to both clobazam and its active metabolite N- desmethylclobazam. These data indicate that in healthy volunteers administered single doses of clobazam as COSF or tablet, the rate and extent of clobazam absorption are similar, and the rate and extent of clobazam metabolism to N-desmethylclobazam are similar. Funding: Funding for this study was provided by Aquestive Therapeutics Inc.