An Open-label, Multi-center, Expanded Access Study of Pasireotide s.c. in Patients With Cushing's Disease.
Condition: Cushing's Disease
MeSH terms: ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion
Intervention: Pasireotide sub-cutaneous
Intervention description: Pasireotide sub-cutaneous was supplied in 1 ml ampoules containing 900 μg, 600 μg, or 300 μg pasireotide per 1 ml of solution and was administered BID. Starting dose was 900 μg and 600 μg for glucose impaired metabolism patients
Intervention MeSH terms: Pasireotide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cushing's disease; Hormone disorder; Cortisol; Adrenocorticotropic hormone; Pituitary tumor; SOM230; adult

Summary:

      This study provided access to pasireotide sc in patients with Cushing's disease.and provided
      additional information for safety and efficacy of pasireotide s.c.
    

Eligibility criteria:

        Inclusion criteria:

          1. Written informed consent obtained prior to any screening procedures

          2. Male or female patients aged 18 years or greater

          3. 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.

          4. 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)

          5. Karnofsky performance status >60 (i.e. requires occasional assistance, but is able to
             care for most of his personal needs)

          6. 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:

          1. Radiotherapy of the pituitary <4 weeks before screening or patient who has not
             recovered from side effects

          2. Patients with compression of the optic chiasm causing acute clinically significant
             visual field defect

          3. Patients with Cushing's syndrome due to ectopic ACTH secretion

          4. Patients with hypercortisolism secondary to adrenal tumors or nodular (primary)
             bilateral adrenal hyperplasia

          5. Patients who have a known inherited syndrome as the cause for hormone over secretion
             (i.e. Carney Complex, McCune-Albright syndrome, MEN-1)

          6. Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)

          7. Patients who have undergone major surgery within 1 month prior to screening

          8. Patients with known gallbladder or bile duct disease, acute or chronic pancreatitis
             (patients with asymptomatic cholelithiasis and asymptomatic bile duct dilation can be
             included)

          9. Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C >8%

         10. 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

         11. 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

         12. 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

         13. 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 suggest any
             increased reproductive risk with the study drugs)

         14. Patients who have participated in any clinical investigation with an investigational
             drug within 1 month prior to screening or patients who have previously been treated
             with pasireotide

         15. Known hypersensitivity to somatostatin analogues

         16. Patients with a history of non-compliance to medical regimens or who are considered
             potentially unreliable or will be unable to complete the entire study

         17. Patients with presence of Hepatitis B surface antigen (HbsAg)

         18. Patients with presence of Hepatitis C antibody test (anti-HCV)