Safety and Pharmacokinetics of Zanubrutinib (BGB-3111) in Healthy Subjects and Those With Impaired Liver Function

• Status: Completed
• Trial end date: 2018-10-19
• Target enrollment: 0
• Participant gender: All

Summary

This study is designed to evaluate the safety and pharmacokinetics of zanubrutinib in subjects with impaired liver function in comparison with healthy subjects

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: BeiGene
• Treatments: Zanubrutinib

Criteria

Inclusion Criteria:

• Male and/or female subjects in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening.

• Subjects must have a body mass index (BMI) between 18 and 40 kg/m2 to participate at screening.

• Female subject must be of non-childbearing potential, i.e. surgically sterile at least 6 months prior to screening with supportive clinical documentation OR post-menopausal must have no regular menstrual bleeding for at least 12 months prior to inclusion. Menopause will be confirmed by a plasma FSH level of >40 IU/L

• Male subjects must agree to practice 2 highly effective methods of birth control at least one method must be barrier technique.

Additional Inclusion Criteria for Healthy Subjects Only:

• In good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests at screening; subjects without diseases/conditions

• Matched with a hepatic impaired patient (mild, moderate or severe, as applicable) using the following criteria: sex, age ±10 years and body mass index (BMI)± 10 kilograms

Additional Inclusion Criteria for Hepatic Impaired Subjects Only:

• History of cirrhosis with supportive documentation (ultrasonography, computed tomography scan, liver biopsy, magnetic resonance imaging, clinical laboratory tests results or physical signs consistent with a clinical diagnosis of liver cirrhosis.

• Child-Pugh Clinical Assessment Score consistent with degree of hepatic impairment.

• Blood pressure of 90 to 155 mmHg (systolic) and 50 to 100 mmHg (diastolic).

• Otherwise considered healthy in general as determined by physical examination findings and laboratory assessments within normal limits.

Exclusion Criteria:

• Subjects with a clinically relevant history or presence of any clinically significant disease.

• History of drug or alcohol abuse within the 12 months prior to dosing.

• A positive human immunodeficiency virus (HIV) Type 1 or 2 test result at screening.

• History of blood donation of 500 mL or more of blood within 2 months prior to screening

• A positive tuberculosis test result.

Additional Exclusion Criteria for Hepatic Impaired Subjects Only:

• Received a liver transplant

• Acute or exacerbating hepatitis

• Active Stage 3 or 4 hepatic encephalopathy

• Previously diagnosed with hepatocellular carcinoma, or a history of cholestatic liver disease or biliary sepsis within the past 2 years.

• Additional Exclusion Criteria for Healthy Subjects Only: A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.

• History of any clinically significant chronic and/or active hepatic disease.