Pharmacokinetic drug interactions of the selective androgen receptor modulator GTx 024(Enobosarm) with itraconazole, rifampin, probenecid, celecoxib and rosuvastatin
SummaryGTx 024 (also known as enobosarm) is a first in class selective androgen receptor modulator being developed for diverse indications in oncology. Preclinical studies of GTx 024 supported the evaluation of several potential drug drug interactions in a clinical setting. A series of open label Phase I GTx 024 drug drug interaction studies were designed to interrogate potential interactions with CYP3A4 inhibitor (itraconazole) a CYP3A4 inducer (rifampin) a pan UGT inhibitor (probenecid) a CYP2C9 substrate (celecoxib) and a BCRP substrate (rosuvastatin) The plasma pharmacokinetics of GTx 024, its major metabolite (GTx 024 glucuronide) and each substrate were characterized in detail. Itraconazole administration had no effect on GTx 024 pharmacokinetics. Likewise, GTx 024 administration did not significantly change the pharmacokinetics of celecoxib or rosuvastatin. Rifampin administration had the largest impact on GTx 024 pharmacokinetics of any co administered agent and reduced the maximal plasma concentration (Cmax) by 23 and the area under the curve (AUC) by 43 Probenecid had a complex interaction with GTx 024 whereby both GTx 024 plasma levels and GTx 024 glucuronide plasma levels (AUC) were increased by co administration of the UGT inhibitor (50 and 112 respectively) Overall, GTx 024 was well tolerated and poses very little risk of generating clinically relevant drug drug interactions.
Investigational New Drugs