A Study to Investigate the Effect of Impaired Hepatic Function on the Pharmacokinetics of Entrectinib in Volunteers With Different Levels of Hepatic Function

• Status: Active, not recruiting
• Trial end date: 2021-09-16
• Target enrollment: 0
• Participant gender: All

Summary

This is a non-randomized, open-label, one treatment, four group, parallel group study to investigate the effect of impaired hepatic function on the pharmacokinetics of entrectinib in participants with different levels of hepatic function. Participants with mild, moderate or severe hepatic impairment ('Mild', 'Moderate' and 'Severe' groups), and control participants with normal hepatic function ('Normal' group) will each receive a single 100 mg dose of entrectinib after consumption of a standardized meal.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Entrectinib

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

• 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.