Bioequivalence of two oral formulations of tebipenem pivoxil hydrobromide in healthy subjects

Abstract

Abstract Tebipenem pivoxil hydrobromide (TBP‐PI‐HBr) is a novel oral carbapenem prodrug of tebipenem (TBP), the active moiety, currently in development for treating serious bacterial infections. This study assessed the bioequivalence (BE) of the clinical trial and registration tablet formulations of TBP‐PI‐HBr and evaluated the effect of food on the pharmacokinetics (PKs) of tebipenem. This was a single center, open‐label, randomized, single‐dose, three‐sequence, four‐period crossover, BE, and food‐effect study. Subjects received single 600 mg oral doses of TBP‐PI‐HBr as the reference clinical trial tablet (treatment A) and test registration tablet (treatment B) formulations in alternating sequence while fasting, and then the test formulation under fed conditions. Whole blood samples were collected predose and at specified intervals up to 24 h postdose to evaluate TBP PK parameters. Safety and tolerability were monitored. Thirty‐six healthy, adult subjects were enrolled and completed the study. The criteria for BE were met for the TBP‐PI‐HBr test (registration tablet) and reference (clinical trial tablet) formulations as the 90% confidence intervals for the geometric mean ratios for TBP area under the curve (AUC)0‐t, AUC0‐inf, and maximum plasma concentration (Cmax) fell within the established 80% to 125% BE limits. Dosing with food had no meaningful effect on TBP PK parameters. Five (14%) subjects reported adverse events (AEs) of mild severity. No deaths, serious AEs, or discontinuations due to AEs were reported, and no clinically relevant electrocardiograms, vital signs, or safety laboratory findings were observed. The study results demonstrate the BE of oral TBP‐PI‐HBr registration and clinical trial tablet formulations and indicate that TBP‐PI‐HBr can be administered without regard to meals.