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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zanubrutinib + Rifabutin | Experimental | Day 1: zanubrutinib Days 3 to 10: rifabutin Day 11: zanubrutinib and rifabutin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zanubrutinib | Drug | Single oral dose of 320 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Zanubrutinib | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | From the date of first study drug administration to 30 days after last dose (up to 3.5 months) |
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Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | BeiGene | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance Clinical Research Unit | Daytona Beach | Florida | 32117 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37145975 | Derived | 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. |
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This was a single-center study with dosing in a fixed sequence. A total of 13 participants were enrolled and 12 completed the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Zanubrutinib + Rifabutin | Single oral dose zanubrutinib 320 mg on Days 1 and 11 in the fasted state and once daily oral rifabutin 300 mg on Days 3 to 10 with food and on Day 11 in the fasted state |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Zanubrutinib on Day 1 |
| |||||||||||||
| Rifabutin on Days 3 to 10 |
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| Zanubrutinib + Rifabutin on Day 11 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Zanubrutinib + Rifabutin | Single oral dose zanubrutinib 320 mg on Days 1 and 11 in the fasted state and once daily oral rifabutin 300 mg on Days 3 to 10 with food and on Day 11 in the fasted state |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Zanubrutinib | 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11 |
|
From the date of first study drug administration to 30 days after last dose (up to 3.5 months)
The safety population included all subjects who received at least 1 dose of zanubrutinib
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Zanubrutinib on Day 1 | Single oral dose zanubrutinib 320 mg on Day 1 | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chromaturia | Renal and urinary disorders | MedDRA 23.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | BeiGene | +1-877-828-5568 | clinicaltrials@beigene.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 16, 2020 | Mar 10, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 12, 2020 | Mar 10, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000629551 | zanubrutinib |
| D017828 | Rifabutin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Rifabutin | Drug | Oral dose of 300 mg once daily |
|
|
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
|
| Primary | AUC From Time Zero to Infinity (AUC0-∞) of Zanubrutinib | 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11 |
|
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Zanubrutinib | 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11 |
|
|
|
|
| Primary | Time to the Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib | 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). | Posted | Median | Full Range | Hours | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11 |
|
|
|
| Primary | Time of the Last Quantifiable Concentration (Tlast) of Zanubrutinib | 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). | Posted | Median | Full Range | Hours | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11 |
|
|
|
| Primary | Apparent Terminal Elimination Half-life (t1/2) of Zanubrutinib | 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). | Posted | Mean | Standard Deviation | Hours | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11 |
|
|
|
| Primary | Apparent Oral Clearance (CL/F) of Zanubrutinib | 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters/hour | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11 |
|
|
|
| Primary | Apparent Volume of Distribution (Vz/F) of Zanubrutinib | 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11 |
|
|
|
| Secondary | 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 | The safety population included all participants who received at least 1 dose of zanubrutinib. | Posted | Count of Participants | Participants | From the date of first study drug administration to 30 days after last dose (up to 3.5 months) |
|
|
|
| 13 |
| 0 |
| 13 |
| 1 |
| 13 |
| EG001 | Rifabutin on Days 3 to 10 | Once daily oral rifabutin 300 mg on Days 3 to 10 | 0 | 13 | 0 | 13 | 6 | 13 |
| EG002 | Zanubrutinib + Rifabutin on Day 11 | Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11 | 0 | 13 | 0 | 13 | 0 | 13 |
| Vessel puncture site haematoma | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information & may request a further delay to protect its IP rights.
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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| Vital sign TEAEs |
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| Physical examination TEAEs |
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| Electrocardiogram TEAEs |
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| Laboratory-related TEAEs |
|