Combination therapy

Inventors

GIBBONS, Jacqueline • MORDENTI, Joyce • DE VRIES, Michiel • KRAUWINKEL, Walter • Ouatas, Taoufik

Assignees

Astellas Pharma Inc • Medivation Prostate Therapeutics LLC

Abstract

This disclosure provides a dosage regimen for co-administration of enzalutamide and a strong CYP3A4 inducer.

Core Innovation

The invention relates to a method of treating prostate cancer in a patient to whom rifampin is administered, comprising co-administering a daily dose of enzalutamide. The regimen is positioned in the context of drug-drug interaction between enzalutamide and a strong CYP3A4 inducer, and the described clinical pharmacology includes exposure comparisons using AUCinf and other exposure measures.

The problem addressed is that rifampin, as a strong CYP3A4 inducer, decreases enzalutamide exposure, including reductions in enzalutamide AUCinf while maintaining comparable Cmax, and is associated with a faster half-life. The data further describe that induction-related changes extend to metabolite exposures, including N-desmethyl enzalutamide metabolites M1 and M2, and that the combined exposure of enzalutamide and metabolite M2 is reduced.

To characterize CYP3A4 induction, the document reports pharmacodynamic evidence using urinary 6β-hydroxycortisol/cortisol ratios to confirm CYP3A4 induction by rifampin by day 8, and indicates minimal induction from enzalutamide alone. The document also reports steady-state rifampin exposure context, including C2h rifampin concentrations.

Claims Coverage

The partial content provides one independent claim. Across the independent claim and its dependent refinements, the coverage centers on co-administration of enzalutamide with rifampin for prostate cancer, with inventive-feature refinements directed to disease states and metastatic combinations.

Claim coverage is directed to a prostate cancer treatment method that co-administers rifampin with a daily 240 mg dose of enzalutamide, with dependent claims specifying castration-resistant and/or hormone-sensitive disease states and adding metastatic combinations.

Stated Advantages

Documented Applications