EDP-420 (also known as EP-013420, or S-013420) is a first-in-class bridged bicyclolide currently in clinical development for the treatment of
respiratory tract infections (RTI) and has previously shown favorable pharmacokinetic (PK) and safety profiles after the administration of single oral doses of a
suspension to healthy volunteers. Here we report its PK profile after the administration of multiple oral doses of a
suspension to healthy adults. Bioequivalence between
suspension and
capsule formulations, as well as the effect of food, is also reported. The most important PK features of
EDP-420 observed in these clinical studies are its long half-life of 17 to 18 h and its high systemic exposure, which support once-daily dosing and treatment durations potentially shorter than those of most other
macrolide antibiotics.
EDP-420 is readily absorbed following
oral administration in both
suspension and
capsule formulations. In the multiple-oral-dose study, steady state was achieved on day 1 by using a loading dose of 400 mg/day, followed by 2 days of 200 mg/day. A high-fat meal had no effect on the bioavailability of
EDP-420 administered in a
capsule formulation.
EDP-420 was well tolerated, with no serious or severe adverse events reported, and no subject was discontinued from the study due to an adverse event. Based on its human PK and safety profiles, together with its in vitro/in vivo activities against common respiratory pathogens,
EDP-420 warrants further development, including trials for clinical efficacy in the treatment of RTI.