Hepatic Insufficiency & Healthy SubjectsPhase 1NCT03465059
Safety and Pharmacokinetics of Zanubrutinib (BGB-3111) in Healthy Subjects and Those With Impaired Liver Function
A Phase 1 study testing Zanubrutinib in people with Hepatic Insufficiency & Healthy Subjects, run by BeiGene at 2 sites in United States.
Trial summary
This study is designed to evaluate the safety and pharmacokinetics of zanubrutinib in subjects with impaired liver function in comparison with healthy subjects Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatic Insufficiency & Healthy Subjects
- What is being tested?
- Zanubrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 May 2018to 19 Oct 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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:
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- 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 locations and contacts
2 sites in 1 country.
United States2 sites
University of Miami
Miami, Florida, 33124
Orlando Clinical Research Center
Orlando, Florida, 32809
About this study
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
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
- Being tested
- Zanubrutinib
- Keywords
- BGB-3111, Zanubrutinib, pharmacokinetics, healthy subjects, hepatic impairment
- Medical subject headings
- Hepatic Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanubrutinibDrug
A single oral dose of 80 mg Zanubrutinib will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Normal Hepatic Function | Experimental | Participants with normal hepatic function will be administered a single oral dose of Zanubrutinib (80 mg). Receives: 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). Receives: 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). Receives: 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). Receives: Drug: Zanubrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Days 1, 2 & 3
Secondary outcomes (1)
Treatment-Emergent Adverse Events (AE)
Percentage of Participants with Treatment-Emergent Adverse Events (AE)
Measured: up to Day 17
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start30 May 2018
- Primary completion19 Oct 2018
- Study completion19 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatic Insufficiency & Healthy SubjectsStudies of the same condition, open and under way.
- More trials run by BeiGeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeiGene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William Novotny, MD, Study director, BeiGene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03465059
- Sponsor's protocol ID
- BGB-3111-107
- Status last verified
- Apr 2020
- First submitted
- 7 Mar 2018
- Last updated
- 24 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32031037
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03465059
- Acronym / sponsor ID
- BGB-3111-107
- Conditions
- Hepatic Insufficiency & Healthy Subjects
- Keywords
- BGB-3111, Zanubrutinib, pharmacokinetics, healthy subjects, hepatic impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- BeiGeneIndustry (pharma, biotech, devices)
- Study start
- 30 May 2018 (actual)
- Primary completion
- 19 Oct 2018 (actual)
- Study completion
- 19 Oct 2018 (actual)
- First posted
- 14 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate the safety and pharmacokinetics of zanubrutinib in subjects with impaired liver function in comparison with healthy subjects
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Normal Hepatic Function | Experimental | Drug: ZanubrutinibParticipants with normal hepatic function will be administered a single oral dose of Zanubrutinib (80 mg). |
| Mild Hepatic Impairment | Experimental | Drug: ZanubrutinibParticipants 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 | Experimental | Drug: ZanubrutinibParticipants 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 | Experimental | Drug: ZanubrutinibParticipants with severe hepatic impairment (Child-Pugh Class C, score of 10 to 15, inclusive) will be administered a single dose of Zanubrutinib (80 mg). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZanubrutinibA single oral dose of 80 mg Zanubrutinib will be administered. | Drug | Mild Hepatic Impairment, Moderate Hepatic Impairment, Normal Hepatic Function, Severe Hepatic Impairment |
Primary outcome
Plasma concentration of Zanubrutinib (BGB-3111) to evaluate protocol specified PK parameters
Time frame: Days 1, 2 & 3
Plasma concentration of Zanubrutinib (BGB-3111) to evaluate Area Under the Plasma Concentration-Time Curve (AUC) of Zanubrutinib
Plasma concentration of Zanubrutinib (BGB-3111) to evaluate protocol specified PK parameters
Time frame: Days 1, 2 & 3
Plasma concentration of Zanubrutinib (BGB-3111) to evaluate Maximum Observed Plasma Concentration (Cmax) of Zanubrutinib
1 secondary outcome
Treatment-Emergent Adverse Events (AE)
Time frame: up to Day 17
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2020.
- Results publication: PubMed 32031037Ou 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.
- Individual participant dataSharing planned: No
Related trials for Hepatic Insufficiency & Healthy Subjects
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Pharmacokinetic Differences, Y-3
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Novotny, MD study director
BeiGene
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zanubrutinib in people with Hepatic Insufficiency & Healthy Subjects, run by BeiGene at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma concentration of Zanubrutinib (BGB-3111) to evaluate protocol specified PK parameters (time frame: Days 1, 2 & 3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03465059, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2020; AzTrials last refreshed its copy on 9 Nov 2026.