| Abstract: | EDP-305 is a farnesoid X receptor (FXR) agonist that selectively activates FXR and is a potential treatment for patients with nonalcoholic steatohepatitis (NASH) with liver fibrosis. Results from preclinical studies indicate that CYP3A4 is the primary enzyme involved in EDP-305 metabolism and that EDP-305 has low potential to inhibit or induce cytochrome (CYP) isoenzymes and drug transporters. Four studies were conducted in healthy volunteers to evaluate the drug-drug interaction (DDI) potential of EDP-305 co-administered with drugs known to be substrates for drug metabolizing enzymes or transporters, and to assess the effect of inhibitors and inducers of CYP3A4 on EDP-305. Results suggest caution when substrates of CYP3A4 are administered concomitantly with EDP-305. A potential for increased exposure is apparent when CYP1A2 substrates with a narrow therapeutic index are administered with EDP-305. In contrast, substrates of drug transporters can be administered concomitantly with EDP-305 with a low potential for interactions. Coadministration of EDP-305 and a combined OC had no relevant effects on plasma concentrations of the combined OC. Co-administration of EDP-305 with strong or moderate inhibitors and inducers of CYP3A4 is not recommended. These results indicate low overall likelihood of interaction of EDP-305 and other substrates through CYP mediated interactions. The interaction potential of EDP-305 with drug transporters was low and of unlikely clinical significance. The EDP-305 DDI profile allows for convenient administration in patients with NASH and other patient populations with comorbidities, with minimal dose modification of concomitant medications. |
