study to determine the prevalence of hypercortisolism in patients with type 2 diabetes and treatment with korlym® (mifepristone) (catalyst)

Conditions: Hypercortisolism; Diabetes Mellitus, Type 2

Summary: this is a phase 4 study with 2 parts: part 1 (prevalence phase) is non-interventional and will assess the prevalence of hypercortisolism in a population with difficult to control type 2 diabetes (t2d) (hemoglobin a1c ≥7.5%) despite receiving standard-of-care therapies. part 2 (treatment phase) is a randomized, prospective, placebo-controlled, double-blind multi-center trial that will assess the safety and efficacy of mifepristone treatment in patients with hypercortisolism who have difficult to control t2d despite receiving standard of care therapies.

this is a phase 4 study with 2 parts at approximately 30 sites in the united states (us). part 1 (prevalence phase) is non-interventional and will assess the prevalence of hypercortisolism in a population with difficult to control t2d (hba1c ≥7.5%) despite receiving standard-of-care therapies. patients from part 1 prevalence phase who meet eligibility requirements can then enroll in part 2 and will be randomized 2:1 to receive mifepristone or placebo once daily with food. randomization will be stratified by presence of adenoma (yes/no). part 2 (treatment phase) is a randomized, prospective, placebo-controlled, double-blind multi-center trial that will assess the safety and efficacy of mifepristone treatment in patients with hypercortisolism who have difficult to control t2d despite receiving standard of care therapies.

Eligibility criteria:
for part 1: inclusion criteria: has difficult to control t2d (hba1c ≥7.5% and ≤11.5%) based on hba1c performed at screening. and taking 3 or more anti-hyperglycemic drugs. or taking insulin and other anti-hyperglycemic drugs. or taking 2 or more anti-hyperglycemic drugs and a.) the presence of 1 or more micro-vascular or macro-vascular complication (retinopathy, diabetic nephropathy and chronic kidney disease, diabetic neuropathy, atherosclerotic heart disease with diabetes); and/or b.) concomitant hypertension requiring 2 or more anti-hypertension medications. • women on oral contraceptive pills (ocps) may be screened but must be willing and able to stop ocps for at least 3 weeks prior to the dexamethasone suppression test. exclusion criteria: * has type 1 diabetes mellitus. * new-onset diabetes less than 1 year. * systemic glucocorticoid medications exposure (excluding inhalers or topical) within 3 months of screening. * is pregnant or lactating. for women of childbearing potential, have a positive pregnancy test before dexamethasone administration. a woman of childbearing potential includes all women \<50 years old, women whose surgical sterilization was performed \<6 months ago, and women who have had a menstrual period in the last 12 months. * on hemodialysis or has end-stage renal disease. * has severe untreated sleep apnea as judged by the investigator. * has excessive alcohol consumption (\>14 units/week for male, \>7 units/week for female) as judged by the investigator. * has severe psychiatric illness by history (such as schizophrenia or dementia) as judged by the investigator. * has severe medical or surgical illness as judged by the investigator. * is a night shift worker, i.e., is awake from approximately 11 pm to 7 am. * has taken any investigational drug within 4 weeks prior to screening, or within less than 5 times the drug's half-life, whichever is longer. * has had the diagnosis of cushing syndrome or has used or plans to use any of the following treatments for cushing syndrome: - mifepristone, metyrapone, osilodrostat, ketoconazole, fluconazole, aminoglutethimide, etomidate, octreotide, larazotide, pasireotide, long-acting octreotide or pasireotide. * has a history of hypersensitivity or severe reaction to dexamethasone for part 2: inclusion criteria: * has completed part 1 of the study with post-dst cortisol level of \>1.8 μg/dl and dexamethasone level ≥140 ng/dl * will have no change in, or initiation of, diabetes medications within 4 weeks prior to first study drug dose exclusion criteria: * has any change in status of exclusion criteria from part 1 * requires inhaled glucocorticoid use and may require systemic glucocorticoids if their condition deteriorates during study * has severe, poorly controlled hypertension at screening (defined as mean systolic bp \>160 mmhg or mean diastolic bp \>100 mmhg); must be able to correct to a bp of \<160/100 mmhg before first dose of study drug * has refractory hypokalemia; must be able to correct to potassium level of ≥4.0 meq/l before first dose of study drug * has poorly controlled hyperthyroidism/hypothyroidism before first dose of study drug (confirmed by tsh or free thyroxine) * has plans for adrenalectomy or adrenal nodulectomy * has renal insufficiency (egfr \<30 ml/min/1.73m2) * has liver test results \>3x uln (alt or ast) or bilirubin \>1.5x uln * takes drugs metabolized by cyp3a and cyp3a substrates with narrow therapeutic ranges * receiving systemic corticosteroids that cannot be discontinued * uses hormonal contraceptives * has a history of unexplained vaginal bleeding, endometrial hyperplasia with atypia, or endometrial carcinoma * is pregnant or lactating * has a known hypersensitivity to mifepristone or any of the product components

Keywords: hypercortisolism diabetes mellitus, type 2 uncontrolled