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

NCT ID: NCT03465059

Last Updated: 2020-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-30
• Study Completion Date: 2018-10-19

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

Conditions

Hepatic Insufficiency & Healthy Subjects

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Normal Hepatic Function

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

Group Type: EXPERIMENTAL

Zanubrutinib

Intervention Type: DRUG

A single oral dose of 80 mg Zanubrutinib will be administered.

Mild Hepatic Impairment

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).

Group Type: EXPERIMENTAL

Zanubrutinib

Intervention Type: DRUG

A single oral dose of 80 mg Zanubrutinib will be administered.

Moderate Hepatic Impairment

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).

Group Type: EXPERIMENTAL

Zanubrutinib

Intervention Type: DRUG

A single oral dose of 80 mg Zanubrutinib will be administered.

Severe Hepatic Impairment

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).

Group Type: EXPERIMENTAL

Zanubrutinib

Intervention Type: DRUG

A single oral dose of 80 mg Zanubrutinib will be administered.

Interventions

Zanubrutinib

A single oral dose of 80 mg Zanubrutinib will be administered.

Intervention Type: DRUG

Eligibility 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.

• 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

• 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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Novotny, MD

Role: STUDY_DIRECTOR

BeiGene

Locations

University of Miami

Miami, Florida, United States

Orlando Clinical Research Center

Orlando, Florida, United States

Countries

United States

References

Ou YC, Preston RA, Marbury TC, Tang Z, Novotny W, Tawashi M, Li TK, Sahasranaman S. A phase 1, open-label, single-dose study of the pharmacokinetics of zanubrutinib in subjects with varying degrees of hepatic impairment. Leuk Lymphoma. 2020 Jun;61(6):1355-1363. doi: 10.1080/10428194.2020.1719097. Epub 2020 Feb 7.

Reference Type: RESULT

PMID: 32031037 (View on PubMed)

Other Identifiers

BGB-3111-107

Identifier Type: -

Identifier Source: org_study_id