An Open-label, Multi-center, Expanded Access Study of Pasireotide s.c. in Patients With Cushing's Disease.

Inclusion criteria

• Written informed consent obtained prior to any screening procedures
• Male or female patients aged 18 years or greater
• Patients with confirmed diagnosis of Cushing's disease as evidenced by mean urinary free cortisol of three 24-hour urine samples collected during the 3-week screening period above the upper limit of the laboratory normal range morning plasma ACTH within the normal or above normal range either MRI confirmation of pituitary adenoma (greater than or equal to 0.6 cm), or inferior petrosal sinus gradient >3 after CRH stimulation for those patients with a microadenoma less than 0.6 cm, or for patients who have had prior pituitary surgery, histopathology confirming an ACTH staining adenoma.
• Patients with de novo Cushing's disease must not be considered as candidates for pituitary surgery (i.e. poor surgical candidates, surgically unapproachable tumors, patients with no visible pituitary tumor, patients who refuse to have surgical treatment)
• Karnofsky performance status >60 (i.e. requires occasional assistance, but is able to care for most of his personal needs)
• For patients on previous medical treatment for Cushing's disease the following washout periods must be completed before screening assessments are performed
• Inhibitors of steroidogenesis (e.g. ketoconazole, metyrapone, rosiglitazone): 1 week
• Dopamine agonists (e.g. bromocriptine, cabergoline): 4 weeks
• Mitotane: 6 months
• Octreotide LAR and Lanreotide autogel: 8 weeks
• Lanreotide SR: 4 weeks
• Octreotide (immediate release formulation): 1 week
• Glucocorticoid receptor inhibitor (mifepristone): 4 weeks

Exclusion criteria

• Radiotherapy of the pituitary 8%
• Patients who have clinically significant impairment in cardiovascular function or are at risk thereof, as evidenced by congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, high grade AV block, history of acute MI less than one year prior to study entry
• QTcF >450 msec at screening
• History of syncope or family history of idiopathic sudden death
• Risk factors for Torsades de Pointes such as uncorrected hypokalemia, uncorrected hypomagnesemia, cardiac failure
• Concomitant disease(s) that could prolong the QT interval such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism, concomitant medication(s) with known risk for TdP
• Patients with liver disease or history of liver disease such as cirrhosis, chronic active hepatitis B and C, or chronic persistent hepatitis, or patients with ALT or AST more than 2 x ULN, serum creatinine >2.0 x ULN, serum bilirubin >1.5 x ULN, serum albumin < 0.67 x LLN at screening
• Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results, such as
• History of immunocompromise, including a positive HIV test result (Elisa and Western blot). An HIV test will not be required, however, previous medical history will be reviewed
• Presence of active or suspected acute or chronic uncontrolled infection
• History of, or current alcohol misuse/abuse in the 12 month period prior to screening
• Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control. If a woman is participating in the trial then one form of contraception is sufficient (pill or diaphragm) and the partner should use a condom. If oral contraception is used in addition to condoms, the patient must have been practicing this method for at least two months prior to screening and must agree to continue the oral contraceptive throughout the course of the study and for one month after the study has ended. Male patients who are sexually active are required to use condoms during the study and for three month afterwards as a precautionary measure (available data do not