PK and Safety of Midostaurin in Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function

Exclusion Criteria

• •Significant neurologic or psychiatric disorder which could compromise participation in the study.
• •History of: seizures requiring anti-convulsant therapy; unstable COPD; GI or rectal bleeding 3 weeks prior to study start; Myocardial Infarction within 12 months; unstable or poorly controlled angina or other clinically significant heart disease; clinically significant urinary obstruction or difficulty voiding; clinically significant ECG abnormalities or long QT-interval syndrome; pancreatic injury or pancreatitis
• •Concurrent severe / uncontrolled medical conditions
• •Significant illness within 2 weeks prior to dosing or hospitalisation within 4 weeks prior to dosing
• •Any surgical or medical condition that may significantly affect absorption, distribution, metabolism or excretion of drugs
• •Clinically significant ECG abnormalities at screening
• •Cotinine levels greater than 500ng/mL (group 1-3) or smokers not willing to limit tobacco or nicotine products equivalent to 10 cigarettes per day (group 4 and 5) for 1 week prior to dosing and throughout hospital confinement
• •Consumption of alcohol within 3 days (group 1-3) or within 2 days (groups 4 and 5) prior to dosing or during the study.
• •Administration of CYP3A4/5 or P-gp inducing or inhibiting drugs within 14 days prior to dosing or during the study
• •Sexually active males unless they use condom during intercourse while taking midostaurin and for at least 3 months after the last exposure to drug.
• •Use of any prescription drug within 2 weeks or over the counter medication within 72 hours prior to dosing
• •Consumption of grapefruit, grapefruit juice, Seville oranges, start fruit / juice within 72 hours prior to dosing
• •Clinical evidence of liver disease or liver injury
• •Positive HBsAg or Hep C test result
• •Symptoms or history of \>=G3 hepatic encephalopathy; surgical portosystemic shunt
• •PTT \>2.5xULN; INR \>3; Total bilirubin \>6mg/dL
• •Evidence of progressive liver disease within 4 weeks prior to starting study
• •Clinical evidence of severe \>=G3 ascites (groups 2 and 3)