Claims for Patent: 10,780,097

Summary for Patent: 10,780,097

Title:	Use of cortisol 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):	Andreas Moraitis
Assignee:	Corcept Therapeutics Inc
Application Number:	US16/109,585
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 will be treated with a glucocorticoid receptor modulator (GRM) to control hyperglycemia secondary to hypercortisolism, the method comprising: Obtaining a potassium level and a morning cortisol level determined from a sample obtained from said patient: and then (a) identifying an adult patient with endogenous Cushing's syndrome having type 2 diabetes mellitus or glucose intolerance who: (i) has greatly increased risk of developing hypokalemia with GRM treatment, said patient having a morning serum cortisol level that is at least 27 micrograms per deciliter (pg/dL), (ii) does not have a lower than normal potassium level; (iii) has not been administered a GRM, and (iv) will be treated with a GRM to control hyperglycemia secondary to hypercortisolism; (b) administering to said identified patient an effective amount of a therapeutic agent for treating hypokalemia, and then (c) administering to the identified patient an initial dose of GRM, whereby the identified patient is treated to control hyperglycemia secondary to hypercortisolism and the risk of developing hypokalemia is reduced or hypokalemia is prevented in the patient, wherein said GRM is mifepristone. 2. The method of claim 1, wherein the patient suffers from ACTH-dependent Cushing's syndrome. 3. The method of claim 1, further comprising administering to the patient the therapeutic agent for treating hypokalemia just before, or at the same time as, increasing the patient's initial GRM dose and administering to the patent a second and higher dose of GRM. 4. The method of claim 1, wherein the therapeutic agent for treating hypokalemia comprises a mineralocorticoid receptor antagonist or a potassium supplement. 5. The method of claim 4, wherein the mineralocorticoid receptor antagonist is spironolactone. 6. The method of claim 1, wherein the initial GRM dose is 300 mg/day, 600 mg/day, 900 mg/day, or 1200 mg/day of mifepristone. 7. The method of claim 1, wherein the patient has failed surgery, or is not a candidate for surgery, for Cushing's syndrome.