Methods: Two multi-center, double-blind, double-dummy trials of adults with ABSSSI randomized patients 1:1 to receive either DLX monotherapy or VAN 15 mg/kg (actual body weight) with AZ for 5 – 14 days. Study 302 used DLX 300mg BID IV only; study 303 used IV DLX for 3 days with a mandatory blinded switch to DLX 450 mg oral BID. Key endpoints were objective response at 48-72 hours with ≥20% reduction in lesion size and Investigator assessment of outcome based on resolution of signs and symptoms at later time-points.
Results: In the 2 studies, 1510 patients were randomized between the 2 groups (DLX or VAN/AZ) including 63% who were male. Mean age ~48 years. 69% of patients had pathogens identified at baseline; S. aureus(62%) was the most frequent isolate with MRSA seen in ~27%. Enterobacteriaceae were identified in ~10% of patients.
Overall, the pooled Phase 3 population included subjects with vascular disease (29.0%), diabetes (11%), and cardiac disease (9.7%). Thirteen percent of subjects were 65 years of age, including 5.5% who were 75 years of age, and 16.2% of subjects had renal impairment (CLcr < 90ml/min). 42% of subjects were obese (BMI ≥ 30 kg/m2). By medical history, the obese subjects had at least twice the rates of vascular disease, metabolism and nutrition disorders, and cardiac disease when compared to the non-obese subjects. Approximately 19% of the obese subjects were diabetic.
Conclusions: Subjects enrolled in the DLX Phase 3 ABSSSI clinical program reflect the challenging ABSSSI patient population commonly seen in clinical practice today. Key patient populations included obese patients, diabetics, and the elderly due to their general risk of infection, including mixed infections. Patients with renal impairment provide challenges in antibiotic selection and dosing, especially when considering the monitoring requirements for vancomycin therapy, as well as the potential for AEs such as nephrotoxicity and infusion site and skin reactions. The obese population acts as natural aggregators of comorbidities and show twice the rate of comorbidities when compared to non-obese patients. These factors are important considerations in antibiotic selection.