Abstract Details

Title Relative Bioavailability of Clobazam Oral Suspension after a Single 20-mg Dose in Healthy Study Volunteers

Topic Epilepsy

Presentation(s) P04 - (-)

Poster/Presentation
Number 209

Objective

Background BACKGROUND: Clobazam 5-, 10-, and 20-mg tablets are available as adjunctive therapy for adult and pediatric patients with Lennox-Gastaut syndrome (LGS).

Design/Methods DESIGN/METHODS: This Phase I, randomized, open-label, two-way crossover study investigated the relative bioavailability, safety, and tolerability of oral suspension vs. oral tablets following a single 20-mg dose to healthy participants (N=30). Doses were administered on Days 1 and 15. Each administration was separated by a 14-day washout. Pharmacokinetic profiles of clobazam and N-desmethylclobazam were obtained from serial plasma concentrations collected over 312 hours post-doses. The relative bioavailability of clobazam suspension vs. that of clobazam tablet was evaluated using bioequivalence criteria: 90% CIs of the ratios of oral suspension to oral tablet for the pharmacokinetic parameters of AUC0-inf and Cmax for clobazam were contained within the interval of 0.80-1.25.

Results RESULTS: The suspension/tablet ratio point estimate and 90% CIs for clobazam were: Cmax=1.19 (1.12 to 1.27); AUC0-last=0.997 (0.977 to 1.02); and AUC0-inf=0.995 (0.976 to 1.01). Thus, bioequivalence criteria were met for AUC0-last and AUC0-inf. However, for Cmax, the upper boundary of the 90% CI was just above the bioequivalence limit of 1.25. All other parameters were similar. The slight increase observed in Cmax is a consequence of the physicochemical properties of the suspension dosage form (designed to deliver drug faster than the tablet) and were not considered clinically meaningful, as two dissimilar dosage forms were compared.

Conclusions CONCLUSIONS: The 20-mg clobazam oral suspension was functionally bioequivalent to 20-mg tablets. Clobazam has a wide therapeutic window and is intended for long-term administration for patients with chronic LGS. Thus, the slight increase in Cmax is clinically insignificant. There were no clinically relevant differences in safety and tolerability between formulations.

Authors/Disclosures
Dwain Tolbert, PhD (Lundbeck LLC) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Panayiotis N. Varelas, MD, PhD, FAAN (Albany Med-Department of Neurology)	Dr. Varelas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Varelas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astra Zeneca -Alexion - Portola. Dr. Varelas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Annexon. Dr. Varelas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astra Zeneca- Alexion-Portola. Dr. Varelas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Marinus. Dr. Varelas has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Varelas has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Giammarco, Mullins & Horton P.C. The institution of Dr. Varelas has received research support from Marinus. The institution of Dr. Varelas has received research support from Bayer. Dr. Varelas has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Varelas has received personal compensation in the range of $5,000-$9,999 for serving as a Rep to the RUC meeting with AAN. Dr. Varelas has received personal compensation in the range of $500-$4,999 for serving as a Speaker at the Annual Meeting with AAN. Dr. Varelas has a non-compensated relationship as a President - Past President with Neurocritical Care Society that is relevant to AAN interests or activities.
	No disclosure on file

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