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

NCT03465059 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: BGB-3111-107
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

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

Keywords

BGB-3111; Zanubrutinib; pharmacokinetics; healthy subjects; hepatic impairment

Outcome Measures

Primary Outcomes (2)

• Plasma concentration of Zanubrutinib (BGB-3111) to evaluate protocol specified PK parameters

  Plasma concentration of Zanubrutinib (BGB-3111) to evaluate Area Under the Plasma Concentration-Time Curve (AUC) of Zanubrutinib

  Days 1, 2 & 3

• Plasma concentration of Zanubrutinib (BGB-3111) to evaluate protocol specified PK parameters

  Plasma concentration of Zanubrutinib (BGB-3111) to evaluate Maximum Observed Plasma Concentration (Cmax) of Zanubrutinib

  Days 1, 2 & 3

Secondary Outcomes (1)

• Treatment-Emergent Adverse Events (AE)

  up to Day 17

Study Arms (4)

Normal Hepatic Function

EXPERIMENTAL

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

Drug: Zanubrutinib

Mild Hepatic Impairment

EXPERIMENTAL

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).

Drug: Zanubrutinib

Moderate Hepatic Impairment

EXPERIMENTAL

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).

Drug: Zanubrutinib

Severe Hepatic Impairment

EXPERIMENTAL

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).

Drug: Zanubrutinib

Interventions

Zanubrutinib DRUG

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

Mild Hepatic Impairment; Moderate Hepatic Impairment; Normal Hepatic Function; Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BeiGene: lead

Study Sites (2)

University of Miami

Miami, Florida, 33124, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Related Publications (1)

• 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.

  PMID: 32031037 RESULT

MeSH Terms

Conditions

Hepatic Insufficiency

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Study Officials

• William Novotny, MD

  BeiGene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2018
• First Posted: March 14, 2018
• Study Start: May 30, 2018
• Primary Completion: October 19, 2018
• Study Completion: October 19, 2018
• Last Updated: April 24, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)