Background: AFN-1252 is a novel inhibitor of FabI, which is essential in Staphylococcus spp. This study evaluated the safety, tolerability and pharmacokinetics of multiple oral doses of AFN-1252 immediate-release tablets.
Methods: Part I evaluated AFN-1252 as a single 200 mg dose in fed versus fasted subjects. Part II evaluated 200, 300 and 400 mg doses of AFN-1252 administered once-daily for 10 days.
Results: Pharmacokinetics indicated good absorption with a median Tmax of 2-3 hours, and a mean t1/2 of 7-10 hours, for all doses. Cmax and AUC responses were non-linear. A high-fat meal reduced AUC0-t and Cmax values by 62% and 48%, respectively, and delayed Tmax by 2.5 hours. All adverse events, including possibly drug-related headache and nausea, were mild or moderate.
Conclusions: Multiple ascending doses of AFN-1252 were safe and well tolerated. AFN-1252 has potential for once- or twice-daily dosing in the treatment of staphylococcal infections.
Keywords: AFN-1252; FabI inhibitor; Immediate–release; Multiple dose; Pharmacokinetics; Phase I; Safety; Staphylococcus aureus.