1699. Efficacy and Safety by BMI Category and Gender in Contezolid and Contezolid Acefosamil Phase 2 and Phase 3 Skin Infection Clinical Trials

Abstract

Abstract Background Contezolid (CZD; MRX-I) is a novel oral (PO) oxazolidinone with potent activity against multidrug-resistant Gram-positive pathogens. Contezolid acefosamil (CZA; MRX-4) is an intravenous (IV) double prodrug of CZD. Nonclinical and initial clinical data indicate CZA and CZD may cause less myelosuppression, particularly with longer duration therapy, and with reduced risk of monoamine oxidase inhibition compared to linezolid (LZD). In 3 CZD Phase 2 (Ph2) and Phase 3 (Ph3) skin infection trials and 1 CZA Ph2 acute bacterial skin and skin structure infection (ABSSSI) study, primary efficacy and overall safety outcomes were comparable to LZD, and the most common treatment emergent adverse events (TEAEs) were gastrointestinal; however, hematologic laboratory abnormalities and TEAEs were less common with CZD and CZA. In June 2021, CZD was approved in China for complicated skin and soft tissue infections (cSSTI). Sequential therapy with CZA IV followed by CZD PO is being evaluated in global Ph3 diabetic foot infection (DFI) and ABSSSI clinical trials. Body weight and gender can affect drug pharmacokinetics (PK) and potentially efficacy and safety outcomes, though in CZA and CZD Phase 1 (Ph1) pharmacokinetics (PK) studies, PK differences between male and female healthy subjects were not considered to be significant. Efficacy and safety outcomes for male and female patients, and between subjects of different body mass index (BMI) were evaluated in completed Ph2 and Ph3 CZD and CZA studies. Methods In 4 CZD and CZA Ph2 and Ph3 skin infection trials, men and women were enrolled with no weight restrictions, and no dose adjustments were made for gender or BMI. Primary efficacy outcomes and occurrence of TEAEs were evaluated for CZD and CZA subjects in 3 BMI categories, and also in male and female subjects. Results Primary efficacy outcomes and occurrence of TEAEs appeared to be similar for CZD and CZA male and female subjects, and also subjects in different BMI categories in 4 skin infection trials. Conclusion In 4 completed Ph2 and Ph3 skin infection clinical trials, primary efficacy and safety outcomes appeared similar for male and female subjects, and for subjects of varying BMI, supporting current Ph3 global DFI and ABSSSI studies which will enroll men and women with no body weight restrictions. Disclosures Edward Fang, MD, MicuRx Pharmaceuticals Inc: Employee Huahui Yang, MS, MicuRx Pharmaceuticals Inc: Employee.