| Exclusion Criteria: | 1) Patients who have received a somatostatin analogue higher than the maximum approved dose within 3 months of Visit 1. (This exclusion criteria is not applicable to patients who are receiving short acting formulation.)
2) Patients receiving radiolabeled somatostatin analogue therapy within the 3 months or any cytotoxic chemotherapy or interferon therapy within the 4 weeks prior to recording baseline symptoms.
3) Patients who have undergone major surgery/surgical therapy for any cause within 1 month or surgical therapy of loco-regional metastases within the last 3 months before recording baseline symptoms.
4) Patients with hepatic artery embolization, chemoembolization or radioembolization (yttrium 90 microspheres) within the last 6 months (1 month if there are other sites of measurable disease), or patients who have undergone cryoablation or radiofrequency ablation of hepatic metastasis within the last 2 months before recording baseline symptoms.
5) Patients who have received radiotherapy for any reason within the last 4 weeks and must have recovered from any side effects of radiotherapy before recording baseline symptoms.
6) Patients who are unwilling to follow dietary restrictions within 3 days of urinary 5-HIAA sample collection or require medications that would interfere with urinary 5-HIAA measurement (e.g. Reserpine, mephenesin carbamate, Lugol's solution).
7) Patients with known malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means.
8) Patients who are not biochemically euthyroid. Diabetic patients on antidiabetic medications whose fasting blood glucose is poorly controlled as indicated by HbA1C > 8%.
9) Patients with symptomatic cholelithiasis.
10) Any of the following cardiac abnormalities:1) QTcF at screening > 450 msec 2) History of syncope or family history of idiopathic sudden death 3) Sustained or clinically significant cardiac arrhythmias 4) Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block 5) Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure.
11) (continuation of # 10) 6) Concomitant medication(s) known to increase the QT interval.
12) Patients with additional active malignant disease within the last five years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix).
13) Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (ELISA and Western blot). A HIV test will not be required; however, previous medical history will be reviewed.
14) Patients with abnormal coagulation [prothrombin time (PT) or activated thromboplastin time (APTT) elevated by 30% above normal limits.]
15) 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 Study Physician.
16) 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 barrier contraception with condoms. If oral contraception is used in addition to condoms, the patient must have been practicing this method for at least two months prior to enrollment and must agree to continue the oral contraceptive throughout the course of the study, and for three months after the study has ended.
17) (Continuation of # 18) Male patients who are sexually active are required to use condoms during the study and for three months afterwards as a precautionary measure (available data do not suggest any increased reproductive risk with the study drugs). Female partners of these male patients must use a secondary barrier contraception.
18) Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing.
19) Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR or s.c. formulations.
20) Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study.
21) Patients who have been previously treated with Pasireotide. |