Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment

Exclusion Criteria

• •Participation in any clinical investigation within 4 weeks prior to dosing
• •Significant acute illness within the two weeks prior to dosing
• •History of immunodeficiency diseases, including a positive HIV
• •History of malignancy of any organ system, treated or untreated, within 5 years
• •Any prior history of keratoacanthoma and/or cutaneous squamous cell carcinoma
• •A known diagnosis of any of the RASopathies, such as NF-1, Noonan syndrome, or related conditions.
• •History of drug or alcohol abuse within the 6 months prior to dosing
• •Smoking: urine cotinine levels below 500 ng/mL on Day -1.
• •Use of drugs known to affect CYP3A4 and/or CYP2C8 including both (strong or moderate) inhibitors and inducers, within 7 days prior to dosing
• •Administration of medications that prolong the QT interval within 4 weeks prior to dosing and until EOT.
• •History or current diagnosis of cardiac disease indicating significant risk of safety
• •Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs.
• •Clinical evidence of liver disease or liver injury
• •History or presence of renal impairment as indicated by abnormal creatinine or BUN values
• •A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody
• •Alcohol or drug abuse within one month prior to dosing or evidence of such
• •History of liver transplantation at any time in the past and is on immunosuppressant therapy.
• •Encephalopathy Grade 3 or worse within 28 days of dosing.
• •History of surgical portosystemic shunt.
• •Life expectancy ≤3 months
• •Other protocol-defined inclusion/exclusion may apply.