1318 - Pharmacokinetics and Safety of Cefepime-Taniborbactam (formerly Cefepime/VNRX-5133) in Subjects with Renal Impairment

Background: Taniborbactam is a novel, non-ß-lactam, ß-lactamase inhibitor with activity against serine (Class A, C, D) and metallo (Class B) ß-lactamases including epidemiologically important carbapenemases. Both cefepime and taniborbactam are predominantly renally excreted and are likely to require dose adjustment in patients with renal impairment and end-stage renal disease (ESRD). The current study was designed to evaluate the pharmacokinetics and safety in patients with renal impairment and ESRD.

Methods: This was a Phase 1, open-label study in subjects with normal renal function (eCL_CR ≥ 90 mL/min) matched to subjects with mild, moderate, and severe renal impairment (eGFR 60-89, 30-59, and < 30 mL/min/1.73m², respectively), and patients with ESRD on hemodialysis. Subjects received a single dose of cefepime 2 g and taniborbactam 500 mg; subjects with ESRD received a single dose before HD and after a 9 day washout period, following HD. PK parameters including AUC_0-inf and total body clearance (CL) were evaluated. Safety assessments included adverse events (AEs), vital signs, clinical laboratory evaluations, electrocardiograms, and physical examinations.

Results: Thirty-three subjects were enrolled; 67% male, 58% white and 39% black/African Americans.  Median age and BMI were 55.0 years and 29.5 kg/m², respectively. For both cefepime and taniborbactam, exposures increased, and CL decreased with increasing renal impairment (see Table). The hemodialysis extraction ratio was 49.7% and 47.4% for taniborbactam and cefepime respectively. No safety signals were observed and there were no serious adverse events.Table


Conclusion: Cefepime and taniborbactam CL is similarly reduced with varying degrees of renal impairment. Dialysis removes a high fraction of both drugs. Dose adjustments recommended for cefepime are appropriate for taniborbactam.