465 A Pharmacokinetic Bridging Study to Compare the Bioavailability of Budesonide Between Budesonide Oral Suspension and ENTOCORT EC in Healthy Subjects

• Published in: The American journal of gastroenterology Vol. 114; no. 1; p. S271
• Main Authors: Song, Ivy, Finkelman, Richard, Lan, Lan
• Format: Journal Article
• Language: English
• Published: New York Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins 01.10.2019
• Subjects: Bioavailability; Crohn's disease; Pharmacokinetics
• ISSN: 0002-9270; 1572-0241
• DOI: 10.14309/01.ajg.0000591392.31133.04

INTRODUCTION:Budesonide oral suspension (BOS; TAK-721) is a viscous formulation of budesonide that is in development for the treatment of eosinophilic esophagitis in adults and adolescents. BOS was granted Breakthrough Designation by the FDA and is currently being evaluated in phase 3 trials. Several budesonide products are approved in the US for other indications, including ENTOCORT EC for mild to moderate active Crohn's disease; thus, the safety of budesonide has been evaluated extensively. The present study compared the bioavailability of BOS with ENTOCORT EC, aiming to provide the pharmacokinetic (PK) bridge to the safety data of ENTOCORT EC.METHODS:Healthy adults (n=22) were enrolled in an open-label, single-center, crossover study. Subjects received two treatments in a randomized sequence with a 48 h washout period between treatments: a single oral dose of BOS 2 mg and a single oral dose of ENTOCORT EC 9 mg. Serial blood samples were collected in each treatment period to determine plasma budesonide concentrations. PK parameters were calculated by non-compartmental analysis and compared between treatments using a mixed effects model with sequence and treatment as fixed effects and subject within sequence as a random effect.RESULTS:Plasma budesonide concentrations showed a faster absorption from BOS compared with ENTOCORT EC. Peak plasma concentrations were achieved ∼1.5 h post-dose for BOS and ∼4 h post-dose for ENTOCORT EC. Systemic exposure to budesonide after a single dose of BOS 2 mg was lower than that observed after a single dose of ENTOCORT EC 9 mg: the geometric mean AUC0-t, AUC0-inf and Cmax of budesonide after BOS 2 mg were 33.6%, 32.9% and 71.1% of those after ENTOCORT EC 9 mg, respectively.CONCLUSION:ENTOCORT EC 9 mg once daily (qd) is approved for induction treatment of Crohn's disease. The proposed clinical dosing regimen for BOS for induction treatment of eosinophilic esophagitis is 2 mg twice daily (bid). When taking into account the different dosing frequencies, the daily AUC and the Cmax of budesonide from BOS 2 mg bid at steady state are estimated to be 67% and 71% of those from ENTOCORT EC 9 mg qd, respectively. These results provide PK bridging data to compare BOS 2 mg bid to ENTOCORT EC with respect to safety information.