The safety and pharmacokinetics of dalbavancin in subjects with renal impairment or end-stage renal disease

Abstract number: 1134_02_95

Dowell J.A., Seltzer E., Krause D., Henkel T.

Objectives:

Dalbavancin is a novel, second generation lipoglycopeptide antibiotic in late stage clinical development for complicated skin and skin structure infections (cSSSI). The weekly dosage used in clinical studies is 1000 mg Day 1/500 mg Day 8. Since dalbavancin will likely be used in patients with various degrees of renal impairment, it is important to determine the safety and pharmacokinetics in this population, as well as to evaluate if a dosage adjustment is necessary.

Methods:

Single intravenous doses of 1000 mg dalbavancin were examined in subjects with mild (CLCR of 50–79 mL/min) and moderate (CLCR of 30–49 mL/min) renal impairment. Doses of 500 mg dalbavancin were studied in subjects with end-stage renal disease (ESRD; dialysis-dependent). Single doses of 500 mg and 1000 mg dalbavancin were studied in subjects with severe renal impairment (CLCR <30 mL/min). Subjects with normal renal function were studied and used as controls. Pharmacokinetic data were analysed using non-compartmental methods; parameters included maximum concentration (Cmax) and area under the plasma concentration time curve (AUC).

Results:

A total of 43 subjects received dalbavancin and were included in the pharmacokinetic analysis (6 mild, 6 moderate, 10 severe, 6 ESRD, and 15 normal). Dalbavancin was well tolerated in each of the renal impairment groups. The majority of adverse events were mild or moderate in severity and unrelated to study drug. There were no related serious adverse events. Dalbavancin pharmacokinetics were similar between subjects with mild and moderate renal impairment and subjects with normal renal function. Concentrations in subjects with ESRD were similar to subjects with normal renal function, indicating compensation in renal insufficiency due to regular dialysis (3 times/week). Subjects with severe renal impairment had increased concentrations and exposure. Concentrations were increased by no more than 40% through the first week post dose, but differences continued to increase through the rest of the profile. AUC was increased almost 2-fold.

Conclusion:

Dalbavancin was well tolerated in subjects with various degrees of renal impairment. Patients with severe renal impairment (CLCR <30 mL/min) may require a modest dosage adjustment. No dosage adjustment is required for patients undergoing regularly scheduled dialysis.