Safety and Pharmacokinetics of Zanubrutinib (BGB-3111) in Healthy Subjects and Those With Impaired Liver Function
- Registration Number
- NCT03465059
- Lead Sponsor
- BeiGene
- Brief Summary
This study is designed to evaluate the safety and pharmacokinetics of zanubrutinib in subjects with impaired liver function in comparison with healthy subjects
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 29
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Normal Hepatic Function Zanubrutinib Participants with normal hepatic function will be administered a single oral dose of Zanubrutinib (80 mg). Mild Hepatic Impairment Zanubrutinib Participants with mild hepatic impairment (Child-Pugh Class A, score of 5 to 6, inclusive) will be administered a single dose of Zanubrutinib (80 mg). Moderate Hepatic Impairment Zanubrutinib Participants with moderate hepatic impairment (Child-Pugh Class B, score of 7 to 9, inclusive) will be administered a single dose of Zanubrutinib (80 mg). Severe Hepatic Impairment Zanubrutinib Participants with severe hepatic impairment (Child-Pugh Class C, score of 10 to 15, inclusive) will be administered a single dose of Zanubrutinib (80 mg).
- Primary Outcome Measures
Name Time Method Plasma concentration of Zanubrutinib (BGB-3111) to evaluate protocol specified PK parameters Days 1, 2 & 3 Plasma concentration of Zanubrutinib (BGB-3111) to evaluate Maximum Observed Plasma Concentration (Cmax) of Zanubrutinib
- Secondary Outcome Measures
Name Time Method Treatment-Emergent Adverse Events (AE) up to Day 17 Percentage of Participants with Treatment-Emergent Adverse Events (AE)
Trial Locations
- Locations (2)
University of Miami
🇺🇸Miami, Florida, United States
Orlando Clinical Research Center
🇺🇸Orlando, Florida, United States