| Exclusion Criteria: | 1) Patients who are being or were treated with octreotide, lanreotide or dopamine agonists with the exception of a single dose of short-acting octreotide or short-acting dopamine agonists. In case of a single dose of short-acting octreotide, the dose should not be used to predict the response to the octreotide treatment. The single dose of short acting octreotide or short-acting dopamine agonists should not be administered in the 3 days prior to randomization.
2) Patients who are being or were treated with GH antagonists
3) De-novo patients not having a visible pituitary adenoma on MRI
4) Patients who have received pasireotide (SOM 230) prior to randomization
5) Patients with compression of the optic chiasm causing any visual field defect for whom surgical intervention is indicated.
6) Patients who require a surgical intervention for relief of any sign or symptom associated with tumor compression
7) Patients who have undergone major surgery/surgical therapy for any cause within 4 weeks of visit 1
8) Patients who have received radiotherapy (except for pituitary irradiation) for any reason in the 4 weeks prior to visit 1 must have recovered from any side effect of radiotherapy
9) Patients who have received pituitary irradiation within the last ten years prior to visit 1
10) Patients who are hypothyroid and not adequately treated with stable doses of thyroid hormone replacement therapy
11) Diabetic patients on antidiabetic medications whose fasting blood glucose is poorly controlled as evidenced by HbA1c >8%
12) Patients with symptomatic cholelithiasis
13) Patients with abnormal coagulation (PT and/or APTT elevated by 30% above normal limits) or patients receiving anticoagulants that affect PT (prothrombin time) or APTT (activated partial thromboplastin time)
14) Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment
15) Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTc > 450 ms, hypokalemia, hypomagnesemia, hypocalcemia, family history of long QT syndrome, or patients receiving a concomitant medication known to prolong QT interval
16) Patients with confirmed central hypothyroidism, central hypoadrenalism and diabetes insipidus, unless they are adequately treated with stable doses of hormone replacement therapy for a minimum of three months prior to study entry (first dose of study medication). Patients with confirmed central hypogonadism unless they are adequately treated with stable doses of hormone replacement therapy for a minimum of three months prior to study entry (first dose of study medication) except in cases where hormones replacement therapy is not indicated.
17) Patients with liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis, or patients with ALT and/or AST more than 2 x ULN, serum creatinine > 2.0 x ULN, serum bilirubin > 2 x ULN, serum albumin < 0.67 x LLN, [Chinese patients need to have normal serum creatinine level (China only)].
18) Patients with WBC <3 x 109/L; Hgb < 90 % LLN; PLT <100 x 109/L
19) Patients who have any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the Investigator or the Sponsor's Medical Monitor
20) Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control. Female patients must use one contraception method and the partner should use a condom. If oral contraception is used, the female patient must have been practicing this method for at least two months prior to the enrollment and must agree to continue the oral contraceptive throughout the course of the study and for three months after the last study drug administration. Male patients who are sexually active are required to use condoms.
21) 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
22) Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to first dosing
23) Known hypersensitivity to somatostatin analogues or any other component of the pasireotide LAR or octreotide LAR formulations
24) Patients with active malignant disease within the last five years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix)
25) Patients with the presence of active or suspected acute or chronic uncontrolled infection
26) 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
27) Patients with a history of alcohol or drug abuse in the 6 month period prior to receiving the study drug |