B-cell Malignancies
Conditions
Brief summary
The primary objective of this study was to assess the steady-state zanubrutinib pharmacokinetics (PK) when co-administered with moderate and strong cytochrome P450 family 3 subfamily A (CYP3A) inhibitors.
Interventions
DRUGZanubrutinib
Capsules administered at a dose and frequency as specified in the treatment arm
DRUGFluconazole
Capsules administered at a dose and frequency as specified in the treatment arm
DRUGDiltiazem
Capsules administered at a dose and frequency as specified in the treatment arm
DRUGVoriconazole
Capsules administered at a dose and frequency as specified in the treatment arm
DRUGClarithromycin
Capsules administered at a dose and frequency as specified in the treatment arm
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Histologically or cytologically confirmed CLL/SLL, MCL, WM, or MZL. 2. Relapsed or refractory disease after at least 1 prior line of systemic therapy. Participants with MZL are required to have failed an anti-CD20 monoclonal antibody-containing chemotherapy regimen. 3. Baseline Eastern Cooperative Oncology Group performance status of 0 to 1. 4. Meet protocol guidelines for adequate bone marrow, kidney, liver, and cardiac function. Key
Exclusion criteria
1. Requirement of chronic treatment with strong and moderate CYP3A inhibitors or inducers or with drugs that are not allowed to be used in combination with diltiazem, clarithromycin, fluconazole, or voriconazole. 2. History of stroke or intracranial hemorrhage (within 6 months of treatment start). 3. Known hypersensitivity or contraindication to zanubrutinib, diltiazem, clarithromycin, fluconazole, or voriconazole. 4. Prior exposure to zanubrutinib or other Bruton tyrosine kinase inhibitor 5. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Arm B: Apparent Terminal Elimination Half-life (t1/2) | Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle) |
| Arm A: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) | Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle) |
| Arm B: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) | Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle) |
| Arm A: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) | Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle) |
| Arm B: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) | Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle) |
| Arm A: Maximum Observed Concentration (Cmax) | Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle) |
| Arm B: Maximum Observed Concentration (Cmax) | Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle) |
| Arm A: Time of the Maximum Observed Concentration (Tmax) | Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle) |
| Arm B: Time of the Maximum Observed Concentration (Tmax) | Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle) |
| Arm A: Apparent Terminal Elimination Half-life (t1/2) | Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Adverse Events (AEs) | From the date of first study drug administration to 30 days after last dose (up to approximately 15 months) | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinical laboratory tests |
Countries
Australia
Participant flow
Recruitment details
This study was conducted at 7 study centers in Australia.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A Cycle 1 (30 days): Participants were administered zanubrutinib at a dose of 320 mg once a day from Day 1 to Day 3; From Day 4 to Day 10, fluconazole was administered once a day at a dose of 400 mg with zanubrutinib at a reduced dose of 80 mg twice a day; On Day 11 and Day 12, zanubrutinib monotherapy was administered at 80 mg twice a day, followed by 320 mg once a day from Day 13 to Day 21; From Day 22 to Day 28, diltiazem was administered once a day at a dose of 180 mg with 80 mg zanubrutinib twice a day; On Day 29 and Day 30, zanubrutinib monotherapy was administered 80 mg twice a day.
Cycles 2 to 6 (28 days each cycle): Zanubrutinib 160 mg twice a day or 320 mg once a day. | 13 |
| Arm B: Zanubrutinib With or Without Strong CYP3A Cycle 1 (30 days): Participants were administered zanubrutinib at a dose of 320 mg once a day from Day 1 to Day 3; From Day 4 to Day 10, voriconazole was administered twice a day at a dose of 200 mg (total daily dose of 400 mg) with zanubrutinib at a reduced dose of 80 mg once a day; On Day 11 and Day 12, zanubrutinib monotherapy was administered at 80 mg once a day, followed by 320 mg once a day from Day 13 to Day 21; From Day 22 to Day 28, clarithromycin was administered twice a day at a dose of 250 mg (total daily dose of 500 mg) with 80 mg zanubrutinib once a day; On Day 29 and Day 30, zanubrutinib monotherapy was administered 80 mg once a day.
Cycles 2 to 6 (28 days each cycle): Zanubrutinib 160 mg twice a day or 320 mg once a day. | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 |
Baseline characteristics
| Characteristic | Arm B: Zanubrutinib With or Without Strong CYP3A | Total | Arm A: Zanubrutinib With or Without Moderate CYP3A |
|---|---|---|---|
| Age, Continuous | 71.8 Years STANDARD_DEVIATION 8.64 | 71.1 Years STANDARD_DEVIATION 9.1 | 70.5 Years STANDARD_DEVIATION 9.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 24 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 23 Participants | 11 Participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 18 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 13 | 0 / 13 |
| other Total, other adverse events | 12 / 13 | 12 / 13 |
| serious Total, serious adverse events | 3 / 13 | 1 / 13 |
Outcome results
Primary
Arm A: Apparent Terminal Elimination Half-life (t1/2)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Population: The PK analysis set included all participants who received at last 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Apparent Terminal Elimination Half-life (t1/2) | Zanubrutinib 80 mg BID + 400 mg fluconazole QD | 2.10 Hours |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Apparent Terminal Elimination Half-life (t1/2) | Zanubrutinib 80 mg BID + 180 mg diltiazem QD | 2.14 Hours |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Apparent Terminal Elimination Half-life (t1/2) | Zanubrutinib 320 mg QD | 2.15 Hours |
Primary
Arm A: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Population: The PK analysis set included all participants who received at last 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) | Zanubrutinib 320 mg QD | 2035.32 h*ng/mL | Geometric Coefficient of Variation 46.97 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) | Zanubrutinib 80 mg BID + 400 mg fluconazole QD | 1911.93 h*ng/mL | Geometric Coefficient of Variation 46.97 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) | Zanubrutinib 80 mg BID + 180 mg diltiazem QD | 1653.07 h*ng/mL | Geometric Coefficient of Variation 44.88 |
Comparison: Arm A: Zanubrutinib alone vs. zanubrutinib + fluconazole90% CI: [0.82, 1.08]
Comparison: Arm A: Zanubrutinib alone vs. zanubrutinib + diltiazem90% CI: [0.66, 0.99]
Primary
Arm A: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Population: The pharmacokinetic (PK) analysis set included all participants who received at last 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) | Zanubrutinib 320 mg QD | 1899.32 h*ng/mL | Geometric Coefficient of Variation 44.95 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) | Zanubrutinib 80 mg BID + 400 mg fluconazole QD | 921.63 h*ng/mL | Geometric Coefficient of Variation 45.8 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) | Zanubrutinib 80 mg BID + 180 mg diltiazem QD | 797.87 h*ng/mL | Geometric Coefficient of Variation 43.05 |
Comparison: Arm A: Zanubrutinib alone vs. Zanubrutinib + fluconazole90% CI: [0.42, 0.56]
Comparison: Arm a: Zanubrutinib alone vs. Zanubrutinib + diltiazem90% CI: [0.34, 0.51]
Primary
Arm A: Maximum Observed Concentration (Cmax)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Population: The PK analysis set included all participants who received at last 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Maximum Observed Concentration (Cmax) | Zanubrutinib 320 mg QD | 520.78 ng/mL | Geometric Coefficient of Variation 39.18 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Maximum Observed Concentration (Cmax) | Zanubrutinib 80 mg BID + 400 mg fluconazole QD | 235.72 ng/mL | Geometric Coefficient of Variation 42.53 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Maximum Observed Concentration (Cmax) | Zanubrutinib 80 mg BID + 180 mg diltiazem QD | 211.06 ng/mL | Geometric Coefficient of Variation 36.59 |
Comparison: Arm A: Zanubrutinib alone vs. zanubrutinib + fluconazole90% CI: [0.35, 0.58]
Comparison: Arm A: Zanubrutinib alone vs. zanubrutinib + diltiazem90% CI: [0.32, 0.51]
Primary
Arm A: Time of the Maximum Observed Concentration (Tmax)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Population: The PK analysis set included all participants who received at last 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Time of the Maximum Observed Concentration (Tmax) | Zanubrutinib 320 mg QD | 2.03 Hours |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Time of the Maximum Observed Concentration (Tmax) | Zanubrutinib 80 mg BID + 400 mg fluconazole QD | 2.93 Hours |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm A: Time of the Maximum Observed Concentration (Tmax) | Zanubrutinib 80 mg BID + 180 mg diltiazem QD | 2.05 Hours |
Primary
Arm B: Apparent Terminal Elimination Half-life (t1/2)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Population: The PK analysis set included all participants who received at last 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Apparent Terminal Elimination Half-life (t1/2) | Zanubrutinib 320 mg QD | 1.79 Hours |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Apparent Terminal Elimination Half-life (t1/2) | Zanubrutinib 80 mg QD + 200 mg voriconazole BID | 2.38 Hours |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Apparent Terminal Elimination Half-life (t1/2) | Zanubrutinib 80 mg QD + 250 mg clarithromycin BID | 2.08 Hours |
Primary
Arm B: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Population: The PK analysis set included all participants who received at last 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) | Zanubrutinib 320 mg QD | 1578.12 h*ng/mL | Geometric Coefficient of Variation 49.53 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) | Zanubrutinib 80 mg QD + 200 mg voriconazole BID | 1376.02 h*ng/mL | Geometric Coefficient of Variation 25.09 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) | Zanubrutinib 80 mg QD + 250 mg clarithromycin BID | 766.71 h*ng/mL | Geometric Coefficient of Variation 60.44 |
Comparison: Arm B: Zanubrutinib alone vs. zanubrutinib + voriconazole90% CI: [0.65, 1.06]
Comparison: Arm B: Zanubrutinib alone vs zanubrutinib + clarithromycin90% CI: [0.4, 0.58]
Primary
Arm B: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Population: The PK analysis set included all participants who received at last 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) | Zanubrutinib 320 mg QD | 1550.40 h*ng/mL | Geometric Coefficient of Variation 49.2 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) | Zanubrutinib 80 mg QD + 200 mg voriconazole BID | 1254.29 h*ng/mL | Geometric Coefficient of Variation 22.36 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) | Zanubrutinib 80 mg QD + 250 mg clarithromycin BID | 763.00 h*ng/mL | Geometric Coefficient of Variation 54.79 |
Comparison: Arm B: Zanubrutinib alone vs. zanubrutinib + voriconazole90% CI: [0.66, 0.99]
Comparison: Arm B: Zanubrutinib alone vs zanubrutinib + clarithromycin90% CI: [0.41, 0.58]
Primary
Arm B: Maximum Observed Concentration (Cmax)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Population: The PK analysis set included all participants who received at last 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Maximum Observed Concentration (Cmax) | Zanubrutinib 320 mg QD | 428.88 ng/mL | Geometric Coefficient of Variation 43.56 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Maximum Observed Concentration (Cmax) | Zanubrutinib 80 mg QD + 200 mg voriconazole BID | 353.11 ng/mL | Geometric Coefficient of Variation 30.23 |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Maximum Observed Concentration (Cmax) | Zanubrutinib 80 mg QD + 250 mg clarithromycin BID | 215.15 ng/mL | Geometric Coefficient of Variation 51.79 |
Comparison: Arm B: Zanubrutinib alone vs. zanubrutinib + voriconazole90% CI: [0.68, 1]
Comparison: Arm B: Zanubrutinib alone vs. zanubrutinib + clarithromycin90% CI: [0.39, 0.64]
Primary
Arm B: Time of the Maximum Observed Concentration (Tmax)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Population: The PK analysis set included all participants who received at last 1 dose of zanubrutinib and had evaluable PK data (at least 1 PK parameter could be calculated).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Time of the Maximum Observed Concentration (Tmax) | Zanubrutinib 320 mg QD | 3.00 Hours |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Time of the Maximum Observed Concentration (Tmax) | Zanubrutinib 80 mg QD + 200 mg voriconazole BID | 2.05 Hours |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Arm B: Time of the Maximum Observed Concentration (Tmax) | Zanubrutinib 80 mg QD + 250 mg clarithromycin BID | 2.08 Hours |
Secondary
Number of Participants Experiencing Adverse Events (AEs)
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinical laboratory tests
Time frame: From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
Population: The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Number of Participants Experiencing Adverse Events (AEs) | At least one SAE | 3 Participants |
| Arm A: Zanubrutinib With or Without Moderate CYP3A | Number of Participants Experiencing Adverse Events (AEs) | At least one TEAE | 12 Participants |
| Arm B: Zanubrutinib With or Without Strong CYP3A | Number of Participants Experiencing Adverse Events (AEs) | At least one TEAE | 12 Participants |
| Arm B: Zanubrutinib With or Without Strong CYP3A | Number of Participants Experiencing Adverse Events (AEs) | At least one SAE | 1 Participants |