Key Exclusion Criteria:

1. Have de novo Cushing??s disease and are surgical candidates for pituitary surgery.
2. Have an acute or unstable medical problem, which could be aggravated by mifepristone treatment.
3. Have received adrenostatic medications including metyrapone, ketoconazole, fluconazole,aminoglutethimide, or etomidate within 1 month of the baseline visit (Day 1). Patients with adrenal carcinoma who have been receiving stable doses of mitotane for at least one month before study entry may continue to receive the same or lower dose of mitotane for the duration of the study.
4. Have received neuromodulator drugs that act at the hypothalamic-pituitary level, such as serotonin antagonists (cyproheptadine, ketanserin, retanserin) dopamine agonists(bromocriptine, cabergoline), GABA agonists (sodium valproate), and somatostatin
receptor ligands (octreotide, pasireotide, lanreotide) within 1 month of the baseline visit(Day 1).
5. Taking medications within 14 days of the baseline visit (Day 1) that a) have a large first pass metabolism that is largely mediated by CYP3A4 and which have a narrow therapeutic margin; and/or b) are strong CYP3A4 inhibitors. Including: cyclosporine, tacrolimus, sirolimus, HIV protease inhibitors non-nucleoside reverse transcriptase inhibitors kinase inhibitors simvastatin, lovastatin, atorvastatin, midazolam (administered orally), triazolam, alprazolam, itraconazole, ketoconazole,nefazodone.
These medications are prohibited during the study. A complete list of contraindicatedmedications and cautionary notes is included in Appendix 18.2
6. Female patients of reproductive potential, who are pregnant or who are unable or unwilling to use medically acceptable, non-hormonal methods of contraception during the study.
7. Have received investigational treatment (drug, biological agent or device) within 30 days of Screening
8. Have a history of an allergic reaction or intolerance to CORLUX (mifepristone)
9. Have a non-endogenous source of hypercortisolemia such as factitious hypercortisolemia (exogenous source of glucocorticoid, iatrogenic Cushing??s syndrome), factitious or therapeutic use of ACTH
10. Have Pseudo-Cushing??s syndrome. Subjects with suspected Pseudo-Cushing??s syndrome such as those with severe obesity, major depression or a history of alcoholism should undergo dexamethasone-CRH test. A cortisol value ??1.4 mcg/dL is consistent with Pseudo-
Cushing??s syndrome.
11. Initiation of an antiresorptive bone active drug such as a bisphosphonate, SERM (selective estrogen receptor modulator), tibolone, calcitonin within 6 months of screening. Subjects
on antiresorptive therapy for greater than 6 months at the time of screening may be enrolled. Anabolic bone agents such as teriparatide or strontium are not allowed within 6 months of screening.
12. Receive PPAR?? agonist drugs (e.g. pioglitazone, rosiglitazone) within 4 months of the baseline visit (Day 1).
13. Initiate or have a change in dose of an antidepressant medication (such as an SSRI or tricyclic compound) within 6 weeks of the baseline visit (Day 1).
14. Initiate or change the dose of any lipid lowering drug within 4 weeks of the baseline visit (Day 1). Subjects who are changed from a prohibited statin drug to an allowed statin must
remain on the new statin for at least 4 weeks prior to the baseline visit (Day 1)
15. Poorly controlled diabetes mellitus defined as HgbA1c ??11% at screening
16. Poorly controlled hypertension defined as a systolic blood pressure > 170 mmHg or diastolic blood pressure > 110 mmHg at screening
17. Have uncorrected hypokalemia (potassium level of <3.5 mEq/L). Subjects should have hypokalemia corrected prior to the baseline visit (Day 1). Spironolactone is allowed to control hypokalemia; spironolactone should not be started to manage elevated blood
pressure.
18. Postmenopausal women with an intact uterus who have experienced unexplained vaginal bleeding within 12 months of Screening are excluded. Individuals who have had vaginal bleeding within 12 months and have undergone a gynecological evaluation are excluded
from participation if they received a diagnosis of endometrial hyperplasia, endometrial carcinoma, or endometrial polyps.
19. Endometrial abnormalities on Transvaginal Ultrasound in:
a. postmenopausal women that include an endometrial thickness >5 mm, ovarian cyst(s) >2 cm, or free fluid pocket of >4cm;
b. premenopausal women that include an endometrial thickness of >2 cm in normally cycling women, an ovarian cyst of >5cm, or a free fluid pocket of >4 cm. If abnormalities are found during cycle days 1-6 the ultrasound may be repeated on days 7-10.
20. Uncontrolled, clinically significant hypothyroidism or hyperthyroidism.
21. Any woman with an intact uterus who has a hemorrhagic disorder or is being treated with an anticoagulant (e.g. warfarin, heparin).
22. Have renal failure as defined by a serum creatinine of ??2.2 mg/dL.
23. Elevated total bilirubin >1.5 ULN, elevated ALT or AST ?? 3X the upper limit of normal.