1121. Bioequivalence of Two Formulations of Oral Tebipenem-Pivoxil Hydrobromide in Healthy Subjects

Abstract

Abstract Background Tebipenem-pivoxil-hydrobromide (TBP-PI-HBr) is a novel oral carbapenem being developed to treat serious bacterial infections including complicated urinary tract infection. The objectives of this study were to assess the bioequivalence (BE) of two tablet formulations of TBP-PI-HBr in healthy adult subjects under fasted conditions and to evaluate the food-drug interactions of the registration drug product. Methods This was an open-label, randomized, single-dose, semi-replicate, 3-sequence, 4-period crossover, BE, and food effect study. Subjects were randomized to one of three sequences where they received a single 600 mg oral dose of TBP-PI-HBr, as either the reference clinical study drug product (Treatment A) or the registration drug product (Treatment B) under fasted conditions. Subsequently, all subjects received a single 600 mg oral dose of TBP-PI-HBr as the registration drug product under fed conditions. There was by a 7-day washout between each period. Whole blood sampling to determine TBP pharmacokinetics (PK) was conducted predose and up to 24 hours post dose in each period. Safety and tolerability were monitored throughout the study. Results Thirty-six healthy, adult male and female subjects were enrolled and completed the study. The TBP-PI-HBr registration product was bioequivalent to the clinical study product (Figure 1). For TBP, 90% confidence intervals (CIs) for AUC0-t, AUC0-inf, and Cmax were within the 80% to 125% BE limits when administered under fasted conditions. A standard high-fat/high-calorie meal had no meaningful effect on the total plasma exposure of TBP after administration of the registration product, thus, overall exposure based on AUC0-t and AUC0-inf was comparable under fed and fasted conditions (Figure 2). Five (14%) subjects reported adverse events of mild severity. No deaths, serious AEs or discontinuations due to AEs were reported, and no clinically relevant ECGs, vital signs or safety laboratory findings were observed. Figure 1. Arithmetic mean plasma TBP concentrations following a 600 mg dose of clinical study drug product (A1 and A2) and registrational drug product (B) – PK population. Figure 2. Arithmetic mean plasma TBP concentrations following a 600 mg dose of registrational drug product (B) under fasted and fed conditions – PK population. Conclusion The TBP-PI-HBr registration product was bioequivalent to the clinical study product under fasted conditions, and no meaningful effect of a high fat meal on TBP PK was observed. Disclosures Vipul K. Gupta, Ph.D., Spero Therapeutics (Employee, Shareholder) Gina Patel, PhD, Spero Therapeutics, Inc. (Consultant) Leanne Gasink, MD, Spero Therapeutics, Inc. (Consultant) Floni Bajraktari, MSc, Spero Therapeutics, Inc. (Employee) Yang Lei, PhD, Spero Therapeutics, Inc. (Employee) Akash Jain, PhD, Spero Therapeutics, Inc. (Employee) Praveen Srivastava, MS, BS, Spero Therapeutics, Inc. (Employee) Angela Talley, MD, Spero Therapeutics, Inc. (Employee)