Clinical trial NCT03465059: Safety and Pharmacokinetics of Zanubrutinib (BGB-3111) in Healthy Subjects and Those With Impaired Liver Function
Official title: A Phase 1, Open-label, Single-dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Zanubrutinib (BGB-3111) in Subjects With Varying Degrees of Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Insufficiency & Healthy Subjects
Keywords: BGB-3111
Zanubrutinib
pharmacokinetics
healthy subjects
hepatic impairment
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-03-14
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

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.

Primary outcomes:
measure: Plasma concentration of Zanubrutinib (BGB-3111) to evaluate protocol specified PK parameters
timeFrame: Days 1, 2 & 3
measure: Plasma concentration of Zanubrutinib (BGB-3111) to evaluate protocol specified PK parameters
timeFrame: Days 1, 2 & 3
Secondary outcomes:
measure: Treatment-Emergent Adverse Events (AE)
timeFrame: up to Day 17
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
affiliation: BeiGene
name: William Novotny, MD
role: STUDY_DIRECTOR
References:
citation: 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.