Concomitant administration of glucocorticoid receptor modulators and cyp3a inhibitors
AssigneeCorcept Therapeutics, Inc.
InventorJoseph K. Belanoff
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AssigneeCorcept Therapeutics, Inc.
InventorJoseph K. Belanoff
Estimating the term…
Applicant provides methods of treating diseases including Cushing's syndrome and hormone-sensitive cancers by concomitant administration of a glucocorticoid receptor modulator (GRM) and steroidogenesis inhibitors, and by concomitant administration of a GRM and CYP3A inhibitors. The GRM may be, e.g., mifepristone; the CYP3A inhibitors or steroidogenesis inhibitors (collectively “inhibitors”) may be, e.g., ketoconazole or itraconazole. Inhibitors may cause toxicity or other serious adverse reactions; concomitant administration of inhibitors with other drugs may increase the risk of such toxicity and adverse reactions due to the inhibitors and/or the other drugs. Applicant has surprisingly found that GRMs may be administered to subjects receiving inhibitors without increasing the risk of adverse reactions; for example, Applicant has found that mifepristone may be concomitantly administered with ketoconazole or itraconazolc, providing safe concomitant administration of the GRM and ketoconazole or itraconazolc. In embodiments, the GRM dose may be reduced during concomitant administration of the GRM with inhibitors.
A method of treating hyperglycemia secondary to hypercortisolism in a patient with Cushing's syndrome, said patient taking an original once-daily (OD) oral dose of 1200 milligrams per day (mg/day) of mifepristone, comprising reducing said original OD oral mifepristone dose of 1200 mg/day to an adjusted OD oral mifepristone dose of 900 mg/day when the patient is receiving concomitant administration of a strong CYP3A inhibitor.
A method of treating symptoms associated with elevated cortisol levels in a patient, said patient taking an original once-daily (OD) oral dose of 1200 milligrams per day (mg/day) of mifepristone, comprising reducing said original OD oral mifepristone dose of 1200 mg/day to an adjusted OD oral mifepristone dose of 900 mg/day when the patient is receiving concomitant administration of a strong CYP3A inhibitor.
A method of treating endogenous Cushing's syndrome in a patient, said patient taking an original once-daily (OD) oral mifepristone dose of 1200 milligrams per day (mg/day), comprising reducing said original OD oral mifepristone dose of 1200 mg/day to an adjusted OD oral mifepristone dose of 900 mg/day when the patient is receiving concomitant administration of a strong CYP3A inhibitor.
A method of safely treating hyperglycemia secondary to hypercortisolism in a patient with Cushing's syndrome, said patient taking an original once-daily (OD) oral dose of 1200 milligrams per day (mg/day) of mifepristone, comprising reducing said original OD oral mifepristone dose of 1200 mg/day to an adjusted OD oral mifepristone dose of 900 mg/day when the patient is receiving concomitant administration of a strong CYP3A inhibitor.
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