HealthyPhase 1NCT04470908

The Effect of Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of Zanubrutinib in Healthy Males

A Phase 1 study testing Zanubrutinib and Rifabutin in people with Healthy and Male, run by BeiGene at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary objective of this study was to determine the effect of the moderate cytochrome P450 3A (CYP3A) inducer rifabutin on the pharmacokinetics (PK) of zanubrutinib in healthy males. Read more about this study

Who is it for?: Ages 18 to 65 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy, Male
What is being tested?: Zanubrutinib and Rifabutin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 1 siteUnited States
Study dates: 29 Jul 2020to 10 Nov 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 65 years
Men only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Males of any race, between 18 and 65 years of age, inclusive.
Male participants in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening
Must have a body mass index (BMI) between 18 and 32 kg/m^2

Who cannot join

Participants with a clinically relevant history or presence of any clinically significant disease
History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed)
History of drug or alcohol abuse within 1 year prior to check-in
Use or intended use of any nonprescription medications/products including vitamins, minerals, herbal/plant-derived preparations within 7 days prior to check-in
A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result and/or a positive human immunodeficiency virus (HIV) at screening
Use of tobacco- or nicotine-containing products within 3 months prior to check-in
Use or intended use of any prescription medications/products within 14 days prior to check-in
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

United States1 site

Covance Clinical Research Unit
Daytona Beach, Florida, 32117

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Fixed-sequence Study to Investigate the Effect of the Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of Zanubrutinib in Healthy Male Subjects

The primary objective of this study was to determine the effect of the moderate cytochrome P450 3A (CYP3A) inducer rifabutin on the pharmacokinetics (PK) of zanubrutinib in healthy males.

Conditions: Healthy, Male
Being tested: Zanubrutinib, Rifabutin
Keywords: Phase 1, Healthy volunteers, Pharmacokinetics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ZanubrutinibDrug
Also called BGB-3111, Brukinsa
Single oral dose of 320 mg
RifabutinDrug
Oral dose of 300 mg once daily

Study groups in NCT04470908
Study group	Role	What they receive
Zanubrutinib + Rifabutin	Experimental	Day 1: zanubrutinib Days 3 to 10: rifabutin Day 11: zanubrutinib and rifabutin Receives: Drug: Zanubrutinib; Drug: Rifabutin

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Zanubrutinib
Measured: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
AUC From Time Zero to Infinity (AUC0-∞) of Zanubrutinib
Measured: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Maximum Observed Plasma Concentration (Cmax) of Zanubrutinib
Measured: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Time to the Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib
Measured: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Time of the Last Quantifiable Concentration (Tlast) of Zanubrutinib
Measured: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Terminal Elimination Half-life (t1/2) of Zanubrutinib
Measured: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Oral Clearance (CL/F) of Zanubrutinib
Measured: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Volume of Distribution (Vz/F) of Zanubrutinib
Measured: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11

Secondary outcomes (1)

Number of Participants Experiencing Adverse Events (AEs)
Adverse events (AEs) and serious adverse events included for summary, AEs that start during or after the first dose, or start prior to the first dose and increases in severity after the first dose, including vital signs, physical examination, electrocardiogram, and laboratory parameters
Measured: From the date of first study drug administration to 30 days after last dose (up to 3.5 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Jul 202010 Nov 2020

First posted14 Jul 2020
Study start29 Jul 2020
Primary completion10 Nov 2020
Study completion10 Nov 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04470908
Sponsor's protocol ID: BGB-3111-112
Status last verified: Oct 2024
First submitted: 10 Jul 2020
Last updated: 26 Oct 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes

Publications

Tariq B, Conto S, Cohen A, Sahasranaman S, Ou YC. A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study of Zanubrutinib with Rifabutin in Healthy Volunteers. Clin Pharmacol Drug Dev. 2023 Aug;12(8):832-838. doi: 10.1002/cpdd.1250. Epub 2023 May 5.
PubMed 37145975

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-label, Fixed-sequence Study to Investigate the Effect of the Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of Zanubrutinib in Healthy Male Subjects
ClinicalTrials.gov ID: NCT04470908
Acronym / sponsor ID: BGB-3111-112
Conditions: Healthy, Male
Keywords: Phase 1, Healthy volunteers, Pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: BeiGeneIndustry (pharma, biotech, devices)
Study start: 29 Jul 2020 (actual)
Primary completion: 10 Nov 2020 (actual)
Study completion: 10 Nov 2020 (actual)
First posted: 14 Jul 2020 (actual)
Results: Posted 14 Dec 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The primary objective of this study was to determine the effect of the moderate cytochrome P450 3A (CYP3A) inducer rifabutin on the pharmacokinetics (PK) of zanubrutinib in healthy males.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Zanubrutinib + Rifabutin	Experimental	Drug: Zanubrutinib, Drug: RifabutinDay 1: zanubrutinib Days 3 to 10: rifabutin Day 11: zanubrutinib and rifabutin

Who may qualify

Ages: 18 to 65 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Males of any race, between 18 and 65 years of age, inclusive.
Male participants in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening
Must have a body mass index (BMI) between 18 and 32 kg/m^2

Key exclusion criteria (8 listed)

Participants with a clinically relevant history or presence of any clinically significant disease
History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed)
History of drug or alcohol abuse within 1 year prior to check-in
Use or intended use of any nonprescription medications/products including vitamins, minerals, herbal/plant-derived preparations within 7 days prior to check-in
A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result and/or a positive human immunodeficiency virus (HIV) at screening

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
ZanubrutinibAlso: BGB-3111, BrukinsaSingle oral dose of 320 mg	Drug	Zanubrutinib + Rifabutin
RifabutinOral dose of 300 mg once daily	Drug	Zanubrutinib + Rifabutin

Primary outcome

Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Zanubrutinib
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
AUC From Time Zero to Infinity (AUC0-∞) of Zanubrutinib
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Maximum Observed Plasma Concentration (Cmax) of Zanubrutinib
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Time to the Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Time of the Last Quantifiable Concentration (Tlast) of Zanubrutinib
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Terminal Elimination Half-life (t1/2) of Zanubrutinib
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Oral Clearance (CL/F) of Zanubrutinib
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Volume of Distribution (Vz/F) of Zanubrutinib
Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11

1 secondary outcome

Number of Participants Experiencing Adverse Events (AEs)
Time frame: From the date of first study drug administration to 30 days after last dose (up to 3.5 months)

Results and safety

Results posted to the registry on 14 Dec 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Zanubrutinib + Rifabutin	13	13

Primary outcome: Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Zanubrutinib

Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11. Geometric mean (Geometric Coefficient of Variation). Unit: h*ng/mL

Measure	Zanubrutinib n = 13	Zanubrutinib + Rifabutin n = 13
Value	2700 (24.8)	1530 (21.4)

Zanubrutinib vs Zanubrutinib + Rifabutin: Ratio of Geometric Least Squares Means: 0.566 (90% CI 0.525 to 0.610)

Population analysed: The pharmacokinetic (PK) population included all participants who received at least 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).

Primary outcome: AUC From Time Zero to Infinity (AUC0-∞) of Zanubrutinib

Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11. Geometric mean (Geometric Coefficient of Variation). Unit: h*ng/mL

Measure	Zanubrutinib n = 13	Zanubrutinib + Rifabutin n = 12
Value	2780 (23.3)	1590 (22.2)

Zanubrutinib vs Zanubrutinib + Rifabutin: Ratio of Geometric Least Squares Means: 0.560 (90% CI 0.532 to 0.589)

Population analysed: The PK population included all participants who received at least 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Zanubrutinib

Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Zanubrutinib n = 13	Zanubrutinib + Rifabutin n = 13
Value	489 (38.1)	253 (33.7)

Zanubrutinib vs Zanubrutinib + Rifabutin: Ratio of Geometric Least Squares Means: 0.518 (90% CI 0.441 to 0.608)

Population analysed: The PK population included all participants who received at least 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).

Primary outcome: Time to the Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib

Time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11. Median (Full Range). Unit: Hours

Measure	Zanubrutinib n = 13	Zanubrutinib + Rifabutin n = 13
Value	1.50 (1.00 to 4.02)	2.00 (1.00 to 8.00)

Population analysed: The PK population included all participants who received at least 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From the date of first study drug administration to 30 days after last dose (up to 3.5 months). Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Zanubrutinib on Day 1	0 of 13 (0%)	1 of 13 (7.7%)	0 of 13
Rifabutin on Days 3 to 10	0 of 13 (0%)	6 of 13 (46.2%)	0 of 13
Zanubrutinib + Rifabutin on Day 11	0 of 13 (0%)	0 of 13 (0%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37145975Tariq B, Conto S, Cohen A, Sahasranaman S, Ou YC. A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study of Zanubrutinib with Rifabutin in Healthy Volunteers. Clin Pharmacol Drug Dev. 2023 Aug;12(8):832-838. doi: 10.1002/cpdd.1250. Epub 2023 May 5.
Individual participant dataSharing planned: Yes

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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.

Study Director principal investigator

BeiGene

1 site 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 and Rifabutin in people with Healthy and Male, run by BeiGene at 1 site 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 3 inclusion and 8 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 26 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Yes. Results are posted in the registry (first posted 14 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Zanubrutinib (time frame: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11). The study lists 8 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 NCT04470908, 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 26 Oct 2024.