A phase I study of the safety, tolerability, and pharmacokinetics of contezolid acefosamil after intravenous and oral administration in healthy Chinese subjects.

Contezolid acefosamil (also known as MRX-4), a prodrug of contezolid, is under development for treatment of multidrug-resistant Gram-positive bacterial infections. A phase I single ascending dose (SAD) and multiple-dose placebo-controlled study was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of contezolid acefosamil in healthy Chinese subjects following intravenous (IV) and oral administration. Adverse events (AEs) and PK parameters were assessed appropriately. All subjects ( = 70) completed the trial. Overall, 67 cases of treatment-emergent adverse events (TEAEs) were observed in 49.1% (27 of 55) of the subjects receiving contezolid acefosamil. All TEAEs were mild in severity. No serious AEs or deaths were reported. After IV SAD (500-2,000 mg), the corresponding of the active drug contezolid increased from 1.95 ± 0.57 to 15.61 ± 4.88 mg/L, AUC from 40.25 ± 10.12 to 129.41 ± 38.30 h·mg/L, median from 2.00 to 2.75 h, and mean from 13.33 to 16.74 h. Plasma contezolid reached steady state on day 6 after multiple IV doses, with an accumulation ratio of 2.20-2.96. Oral SAD of 500 and 1,500 mg resulted in contezolid of 8.66 ± 2.60 and 37.10 ± 8.66 mg/L, AUC of 30.44 ± 7.33 and 162.36 ± 47.08 h·mg/L, and median of 2.50 and 2.98 h. Contezolid reached steady state on day 5 after multiple oral doses of 1,500 mg without significant accumulation. Contezolid and AUC increased with the dose of contezolid acefosamil. The good safety and PK profiles in this SAD and multiple-dose study can support further clinical development of contezolid acefosamil.