A Phase III multicentre, randomized, double-blind trial to evaluate the efficacy and safety of oral contezolid versus linezolid in adults with complicated skin and soft tissue infections

Abstract

Abstract Objectives Contezolid is a novel oxazolidinone antibacterial agent for managing infections caused by aerobic and anaerobic Gram-positive bacteria including methicillin-resistant strains. A Phase III, multicentre, randomized, double-blind, active-controlled trial evaluated the efficacy and safety of contezolid versus linezolid in adults with complicated skin and soft tissue infections (cSSTIs). Methods Adult patients with cSSTI were randomized in a ratio of 1:1 to receive contezolid 800 mg or linezolid 600 mg q12h for 7–14 days. Clinical cure rate and safety were assessed at the test of cure (TOC) visit in the full analysis set (FAS) and clinical evaluable (CE) population. Non-inferiority was defined as a lower limit of the 95% CI around the treatment difference of clinical cure rates greater than −10%. Chinadrugtrials.org.cn registration identifier: CTR20150855. Results Clinical cure rates at TOC indicated non-inferiority of contezolid 800 mg to linezolid 600 mg q12h for patients in the FAS with clinical evaluation, FAS, and CE populations: 92.8% (271/292) versus 93.4% (284/304) (difference −0.6%, 95% CI: −4.7% to 3.5%), 81.4% (271/333) versus 84.5% (284/336) (difference −3.1%, 95% CI: −8.8% to 2.6%) and 90.5% (267/295) versus 90.1% (282/313) (difference 0.4%, 95% CI: −4.3% to 5.1%). Contezolid and linezolid showed similar efficacy for the cSSTIs caused by methicillin-susceptible or methicillin-resistant Staphylococcus aureus. Contezolid demonstrated significant lower incidence of leucopenia (0.3% versus 3.4%) and thrombocytopenia (0% versus 2.3%) than linezolid. The frequency of treatment-emergent adverse events was comparable between the two groups. Conclusions Contezolid 800 mg q12h is as effective as linezolid for treatment of cSSTIs in adults, but safer than linezolid in terms of haematological abnormalities.