Evaluation of the Potential for Cytochrome P450 and Transporter-Mediated Drug–Drug Interactions for Firsocostat, a Liver-Targeted Inhibitor of Acetyl-CoA Carboxylase

Firsocostat is an oral, liver-targeted inhibitor of acetyl-CoA carboxylase in clinical development for the treatment of metabolic dysfunction-associated steatohepatitis. This work evaluated the potential drug–drug interactions (DDIs) of firsocostat as a victim and as a perpetrator, to inform concomitant medication use. In this phase I study, healthy participants (n = 13–30 in each of four cohorts) received firsocostat alone or in combination with either victims or perpetrators of cytochrome P450 (CYP) enzymes and drug transporters to evaluate firsocostat as both a victim and perpetrator of DDIs, respectively. Overall, 80 participants completed the study. As a victim of DDI, firsocostat plasma exposure (area under the plasma concentration-time curve [AUC] from 0 to infinity [AUC∝]) was 19-fold, 22-fold, 63