Corcept Therapeutics Incorporated
CONCOMITANT ADMINISTRATION OF GLUCOCORTICOID RECEPTOR MODULATOR RELACORILANT AND CYP2C8 SUBSTRATES

Abstract:

Relacorilant is useful in the treatment of cancer and hypercortisolism. Many drugs useful in treating cancer or hypercortisolism are metabolized by CYP2C8 enzymes. The effects of concomitant administration of relacorilant and a CYP2C8 substrate are disclosed herein. Relacorilant potently inhibited CYP2C8 in an in vitro test, indicating that co-administration of relacorilant and a CYP2C8 substrate would be expected to increase the CYP2C8 substrate plasma exposure more than five-fold in vivo. Significant reductions in CYP2C8 substrate doses would be expected to be required when administered with relacorilant. Surprisingly, no such increase in plasma exposure was seen in human studies. Applicant discloses that relacorilant may be safely co-administered with unmodified doses of CYP2C8 substrates such as pioglitazone, rosiglitazone, and enzalutamide. Relacorilant and unmodified doses of enzalutamide may be co-administered to treat cancer, e.g., prostate cancer. Relacorilant and unmodified doses of pioglitazone or rosiglitazone may be co-administered to treat cancer or hypercortisolism.