Dalbavancin safety in the phase 2/3 clinical development program

Introduction

Dalbavancin (DAL) is a novel, next-generation lipoglycopeptide with a pharmacokinetic profile that allows weekly dosing. The safety of DAL in the treatment of complicated skin and soft tissue infections was demonstrated versus comparators (COMP) in the phase 2/3 clinical development program.

Methods

Safety was assessed by analyzing adverse events (AEs), laboratory parameters, vital signs, and ECGs. Safety analyses were conducted on the intent-to-treat (ITT) population, using descriptive statistics only (consistent with ICH Guidance). COMP included linezolid, cefazolin, and vancomycin.

Results

Of 1,699 patients in the phase 2/3 integrated database, 1126 patients received DAL. Demographic characteristics were similar between the treatment groups. The majority of patients were aged <65 years, male (60.2% DAL vs 58.8% COMP), and Caucasian (71.1% DAL vs 75% COMP). The safety and tolerability were good and comparable with each of the comparators separately and in toto. No compound-specific or unique toxicity was identified. The duration of AEs in patients treated with DAL was similar to that of COMP (median duration, 4 days vs 5.5 days for treatment-related AEs and 3 days vs 4 days for all AEs, respectively) (Figure 1). There was no hepatotoxic or renal signal in an examination of abnormalities in ALT, AST, BUN, and creatinine. The percentage of patients with abnormal hematology values was low and similar between treatment groups. No QT effect was demonstrated. Safety in relevant subpopulations (such as elderly, diabetic patients) was demonstrated.

Figure 1

Conclusion

Dalbavancin is a well-tolerated lipoglycopeptide, with an AE profile similar to comparators in type and duration of AEs.