A Phase l Study to Evaluate the Pharmacokinetics and Safety Pasireotide in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Volunteers

Exclusion Criteria

• •Subjects eligible for this study must not meet any of the following criteria:
• •1. Clinically significant abnormal laboratory values at the screening evaluation or at the baseline re-evaluation, excluding those normally associated with mild to severe degree of renal impairment or the primary cause of renal insufficiency
• •2. Use of any over-the-counter medications or vitamins or herbal/natural supplements during 2 weeks prior to dosing (acetaminophen is acceptable, and must be documented in the Concomitant Medications/Non-Drug Therapies page of the CRF)
• •3. Current medical history of the following:
• •* Sustained or clinically significant cardiac arrhythmias
• •* History of syncope or family history of idiopathic sudden death
• •* Risk factors for torsades de pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high grade AV block
• •* Screening QTcF \> 450ms
• •* 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
• •* Concomitant medications known to increase the QT interval
• •4. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation
• •5. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing or other amount considered to compromise the health of the subject if previous history of anemia exists
• •6. Significant acute illness within the two weeks prior to dosing
• •7. History of immunocompromise, including a positive HIV (ELISA and Western blot) test result
• •8. History of allergies to the investigational compound/compound class being used in the study
• •9. A positive Hepatitis B surface antigen (HBsAg) or positive HCV antibody
• •10. History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations
• •11. History of liver disease, such as cirrhosis or chronic active hepatitis B and C.
• •12. Known gallbladder or bile duct disease, acute or chronic pancreatitis
• •13. Baseline ALT or AST \> ULN
• •14. Baseline total bilirubin \> 1.5x ULN
• •15. Subjects on dialysis
• •16. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 5 times the terminal half-life of study treatment (6 days). Highly effective contraception methods include:
• •* Total abstinence or
• •* Male or female sterilization or
• •* Combination of any two of the following (a+b or a+c, or b+c):
• •* Use of oral, injected or implanted hormonal methods of contraception
• •* Placement of an intrauterine device (IUD) or intrauterine system (IUS)
• •* Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
• •17. Sexually active males unless they use a condom during intercourse while taking drug and for 5 half-lives (6 days) after stopping SOM230 medication and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
• •18. Potentially unreliable or vulnerable subjects (e.g. person kept in detention) and those judged by the investigator to be unsuitable for the study.