Phase II Clinical Study of BC-3781, a Pleuromutilin Antibiotic, in Treatment of Patients with Acute Bacterial Skin and Skin Structure Infections

Abstract

ABSTRACT This study investigated the potential of the novel systemic pleuromutilin antibiotic BC-3781 to treat patients with an acute bacterial skin and skin structure infection (ABSSSI) caused by a Gram-positive pathogen. Patients were randomized to intravenous BC-3781 100 mg, BC-3781 150 mg, or vancomycin 1 g every 12 h. Response to treatment was assessed daily and at test of cure (TOC). The primary endpoint was the clinical success rate at TOC in the modified intent-to-treat (MITT) and clinically evaluable (CE) analysis populations. Baseline characteristics, including the frequency of methicillin-resistant Staphylococcus aureus (MRSA), were comparable between the different treatment groups. Of 210 patients randomized, 186 (88.6%) patients completed the study. Clinical success at TOC in the CE population occurred in 54 (90.0%) patients in the BC-3781 100-mg group, 48 (88.9%) in the BC-3781 150-mg group, and 47 (92.2%) in the vancomycin group. At day 3, the clinical response rate was similar across the three treatment groups. Six patients discontinued study medication following an adverse event. The incidence rate for drug-related adverse events was lower for patients receiving BC-3781 (34.3% and 39.4% in the 100-mg and 150-mg groups, respectively) than those receiving vancomycin (53.0%). When BC-3781 was used to treat ABSSSIs caused by a Gram-positive pathogen, including MRSA, clinical success rates were comparable to those of the comparator, vancomycin. BC-3781 was generally well tolerated. These results provide the first proof of concept for the systemic use of a pleuromutilin antibiotic for the treatment of ABSSSIs.