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

BeiGene

Status and phase: Completed; Phase 1

Conditions: Hepatic Insufficiency & Healthy Subjects

Treatments: Drug: Zanubrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03465059

BGB-3111-107

Details and patient eligibility

About

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

Enrollment: 29 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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29 participants in 4 patient groups

Normal Hepatic Function

Experimental group

Description:

Participants with normal hepatic function will be administered a single oral dose of Zanubrutinib (80 mg).

Treatment:

Drug: Zanubrutinib

Mild Hepatic Impairment

Experimental group

Description:

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).

Treatment:

Drug: Zanubrutinib

Moderate Hepatic Impairment

Experimental group

Description:

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).

Treatment:

Drug: Zanubrutinib

Severe Hepatic Impairment

Experimental group

Description:

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).

Treatment:

Drug: Zanubrutinib