Claims for Patent: 10,231,983

Summary for Patent: 10,231,983

Title:	Use of ACTH in assessment and prophylactic treatment of hypokalemia associated with glucocorticoid receptor modulator treatment of Cushing's syndrome patients
Abstract:	This invention provides new methods for a) identifying Cushing's Syndrome patients at high risk of developing hypokalemia during glucocorticoid receptor modulator (GRM) treatment, and b) for prophylactically treating such patients to prevent, or reduce the severity of, hypokalemia. Patients at such high risk may be identified prior to their developing hypokalemia. Such a patient may be an adult patient with endogenous Cushing's Syndrome having type 2 diabetes mellitus or glucose intolerance to control hyperglycemia secondary to hypercortisolism. Patients may be identified by an above-threshold level of ACTH or cortisol in a patient sample taken post-GRM administration or pre-GRM administration, respectively. Upon identifying such a patient prior to the development of low potassium, the present methods provide for prophylactically treating the patient by administration of one or more hypokalemia treatments concurrently with an increased dose of GRM or with an initial dose of GRM to prevent hypokalemia.
Inventor(s):	Moraitis; Andreas (Menlo Park, CA)
Assignee:	Corcept Therapeutics, Inc. (Menlo Park, CA)
Application Number:	16/109,561
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,231,983
Patent Claims:	1. A method for reducing the risk of developing hypokalemia or preventing the development of hypokalemia in an adult patient with endogenous Cushing's syndrome having type 2 diabetes mellitus or glucose intolerance, wherein the patient is being, or will be, treated with a glucocorticoid receptor modulator (GRM) to control hyperglycemia secondary to hypercortisolism, the method comprising: (a) administering to the patient an effective amount of a therapeutic agent for treating hypokalemia, wherein the patient prior to step (a) has been administered multiple doses of a first dose of the GRM over a time period of about 7 days to about 21 days, and the patient's morning serum ACTH level is at least about 112 pg/mL after said multiple doses of GRM, and wherein the patient does not have a lower than normal potassium level, whereby the patient is treated to control hyperglycemia secondary to hypercortisolism and the risk of developing hypokalemia is reduced or hypokalemia is prevented in the patient. 2. The method of claim 1, wherein the patient suffers from ACTH-dependent Cushing's syndrome. 3. The method of claim 1, wherein step (a) comprises administering to the patient the therapeutic agent for hypokalemia just before, or at about the same time as, increasing the patient's GRM dose and administering to the patient a second and higher dose of GRM. 4. The method of claim 1, wherein the patient prior to step (a) has been administered the first dose of GRM for at least two weeks. 5. The method of claim 1, wherein the therapeutic agent for treating hypokalemia comprises a mineralocorticoid receptor antagonist or a potassium supplement. 6. The method of claim 5, wherein the mineralocorticoid receptor antagonist comprises spironolactone. 7. The method of claim 1, wherein the GRM comprises mifepristone. 8. The method of claim 7, wherein the first dose of mifepristone is 300 mg/day, 600 mg/day, 900 mg/day, or 1200 mg/day of mifepristone. 9. The method of claim 1, wherein the patient has failed surgery, or is not a candidate for surgery, for Cushing's syndrome. 10. The method of claim 3, wherein the GRM comprises mifepristone. 11. A method for reducing the risk of developing hypokalemia or preventing the development of hypokalemia in an adult patient with endogenous Cushing's syndrome having type 2 diabetes mellitus or glucose intolerance, wherein the patient is being, or will be, treated with a glucocorticoid receptor modulator (GRM) to control hyperglycemia secondary to hypercortisolism, the method comprising: (a) administering to the patient an effective amount of a therapeutic agent for treating hypokalemia, wherein the patient prior to step (a) has been administered multiple doses of a first dose of the GRM over a time period of about 7 to about 21 days, wherein the patient's morning serum ACTH level after having received said multiple doses of GRM is at least about 1.5 times the patient's baseline morning serum ACTH level, wherein said baseline morning serum ACTH level is determined prior to GRM administration, and wherein the patient does not have a lower than normal potassium level, whereby the patient is treated to control hyperglycemia secondary to hypercortisolism and the risk of developing hypokalemia is reduced or hypokalemia is prevented in the patient. 12. The method of claim 11, wherein the patient suffers from ACTH-dependent Cushing's syndrome. 13. The method of claim 11, wherein step (a) comprises administering to the patient the therapeutic agent for hypokalemia just before, or at about the same time as, increasing the patient's GRM dose and administering to the patient a second and higher dose of GRM. 14. The method of claim 11, wherein the patient's morning serum ACTH level after having received the multiple doses of the first dose of GRM administration is at least about 2 times the patient's morning serum ACTH level prior to starting GRM administration. 15. The method of claim 11, wherein the patient prior to step (a) has been administered the first dose of GRM for at least two weeks. 16. The method of claim 11, wherein the therapeutic agent for treating hypokalemia comprises a mineralocorticoid receptor antagonist or a potassium supplement. 17. The method of claim 16, wherein the mineralocorticoid receptor antagonist is spironolactone. 18. The method of claim 11, wherein the GRM comprises mifepristone. 19. The method of claim 18, wherein the first dose is 300 mg/day, 600 mg/day, 900 mg/day, or 1200 mg/day of mifepristone. 20. The method of claim 11, wherein the patient has failed surgery, or is not a candidate for surgery, for Cushing's syndrome. 21. The method of claim 13, wherein the GRM comprises mifepristone. 22. A method for treating Cushing's syndrome and reducing the risk of developing hypokalemia or preventing the development of hypokalemia in a patient with Cushing's syndrome, the method comprising: (a) administering to the patient an effective amount of a therapeutic agent for treating hypokalemia, wherein the patient prior to step (a) has been administered multiple doses of a first dose of a glucocorticoid receptor modulator (GRM) over a time period of about 7 to about 21 days, wherein (1) the patient's morning serum ACTH level is at least about 112 pg/mL after said multiple doses of GRM, and wherein the patient does not have a lower than normal potassium level; or (2) the patient's morning serum ACTH level after having received said multiple doses of GRM is at least about 1.5 times the patient's baseline morning serum ACTH level, wherein said baseline morning serum ACTH level is determined prior to GRM administration, and wherein the patient does not have a lower than normal potassium level, whereby the patient is treated for Cushing's syndrome and the risk of developing hypokalemia is reduced or hypokalemia is prevented in the patient. 23. The method of claim 22, wherein the patient suffers from ACTH-dependent Cushing's syndrome. 24. The method of claim 22, wherein step (a) comprises administering to the patient the therapeutic agent for hypokalemia just before, or at about the same time as, increasing the patient's GRM dose and administering to the patient a second and higher dose of GRM. 25. The method of claim 22, wherein the patient prior to step (a) has been administered the first dose of GRM for at least two weeks. 26. The method of claim 22, wherein the therapeutic agent for treating hypokalemia comprises a mineralocorticoid receptor antagonist or a potassium supplement. 27. The method of claim 26, wherein the mineralocorticoid receptor antagonist comprises spironolactone. 28. The method of claim 22, wherein the GRM comprises mifepristone. 29. The method of claim 28, wherein the first dose of mifepristone is 300 mg/day, 600 mg/day, 900 mg/day, or 1200 mg/day of mifepristone. 30. The method of claim 24, wherein the GRM comprises mifepristone.