What happens to a medicine (entrectinib) when given to people with unhealthy livers

All participants:

• A body mass index (BMI) between 18.0 and 38.0 kg/m2, and weighing at least 50 kg
• Agreement to comply with measures to prevent pregnancy and restrictions on sperm donation.

Participants with normal hepatic function:

• Normal hepatic function and no history of clinically significant hepatic dysfunction.
• Healthy for age-group in the opinion of the Investigator.

Participants with hepatic impairment:

• Mild, moderate or severe hepatic dysfunction (i.e. Child-Pugh A, B or C, NCIODWG Mild, Moderate or Severe) arising from cirrhosis of the liver as the result of parenchymal liver disease.
• Stable hepatic function.

• Transjugular intrahepatic portosystemic shunt or other porta-caval shunt.
• A history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers.
• Recent history or signs of severe hepatic encephalopathy (e.g., a portal systemic encephalopathy score >2).
• Advanced ascites or ascites which require emptying and albumin supplementation.
• Hepatocellular carcinoma, acute liver disease or serum ALT or AST not consistent with stable disease.
• Recipient of a liver transplant.
• Uncontrolled hypertension.
• Clinically significant impairment of renal function.
• A history of gastrointestinal surgery or other gastrointestinal disorder that might affect absorption of medicines from the gastrointestinal tract.
• Clinically significant change in health status, or any major illness, or clinically significant acute infection or febrile illness.
• Women who are pregnant or lactating.
• Presence of any abnormal ECG finding, which is clinically significant.
• Use of moderate or potent inhibitors or inducers of cytochrome P450 3A4 enzyme.
• Participation in any other clinical study involving administration of an investigational medicinal product or use of an unapproved device.
• A positive test result for human immunodeficiency virus (HIV).
• Known history of clinically significant hypersensitivity, or severe allergic reaction, to entrectinib or related compounds or other excipients in the entrectinib formulation.