Treatment for Endogenous Cushing's Syndrome

Inclusion Criteria

• •1. Male or female ≥18 years of age
• •2. Able to provide written informed consent prior to any study procedures being performed; eligible subjects must be able to understand the informed consent form prior to inclusion into the study.
• •3. Confirmed diagnosis of newly diagnosed, persistent or recurrent Cushing's disease (CD) or endogenous CS of other etiology if subjects are not candidates for surgery or radiotherapy within the 18 months after enrollment.
• •Previous medical records will be collected and used to support the diagnosis of CD or endogenous CS of other etiology, including the following etiologies:
• •* Ectopic adrenocorticotropic hormone (ACTH) secretion, i.e. ACTH not of pituitary origin
• •* Ectopic corticotropin-releasing hormone (CRH) secretion
• •* Adrenal-dependent CS (i.e. adrenal adenoma (NOT carcinoma), adrenal hyperplasia, etc.)
• •* Etiology unknown.
• •4. Must have elevated mean 24 hour UFC levels ≥1.5X ULN based on the normative range of the central lab assay and on a minimum of four measurements from adequately collected urine.
• •5. In addition to elevated mean UFC, presence of abnormal values from one of the following tests:
• •* Abnormal DST: Elevated 8 AM serum cortisol ≥1.8 micrograms/dL (50 nmol/L) after 1 mg dexamethasone orally at 11 PM the evening prior (if not conducted already in the diagnostic workup of the subject within the previous 2 months before start of Screening Phase; in that case previous test results and details of conduct will need to be available by the Baseline Visit)
• •* Elevated late night salivary cortisol concentrations (at least two measurements) \>ULN
• •6. Previously irradiated subjects with CD or endogenous CS of other etiology will be allowed as long as the radiation treatment occurred \> 4 years ago and subjects have not exhibited evidence for improvement in their underlying CD for 6 months prior to the Screening visit. The total number of previously irradiated subjects enrolled in this study will not exceed 10.
• •7. Subjects with CD or CS of other etiology who are not candidates for surgery, refuse surgery, or in whom surgery will be delayed for at least 18 months following enrollment. Subjects may be allowed to participate in the trial while awaiting surgery, but must agree to complete this study prior to surgery.
• •8. Subjects on treatment for CD or endogenous CS of other etiology for whom treatment has been inadequate or not well tolerated must agree to minimum washout periods prior to the Baseline Visit as specified.