| Primary | Arm A: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) | | 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). | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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 (QD) 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 (BID); 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. |
| | | Title | Denominators | Categories |
|---|
| Zanubrutinib 320 mg QD | | | | Zanubrutinib 80 mg BID + 400 mg fluconazole QD | | | | Zanubrutinib 80 mg BID + 180 mg diltiazem QD | |
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| Arm A: Zanubrutinib alone vs. Zanubrutinib + fluconazole | | | | | Ratio of geometric least squares mean | 0.49 | | | 2-Sided | 90 | 0.42 | 0.56 | | | | | Equivalence | Two one sided tests procedure by estimation of ratio of geometric means and 90% CI; exponential transformation from estimated difference in natural logarithm scale obtained from linear mixed effect model with treatment as a fixed effect and participant as a random effect. | | |
|
| Primary | Arm B: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) | | 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). | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| Primary | Arm A: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) | | 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). | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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 (QD) 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 (BID); 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. |
| |
| Primary | Arm B: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) | | 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). | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| Primary | Arm A: Maximum Observed Concentration (Cmax) | | 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). | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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 (QD) 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 (BID); 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. |
| |
| Primary | Arm B: Maximum Observed Concentration (Cmax) | | 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). | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| Primary | Arm A: Time of the Maximum Observed Concentration (Tmax) | | 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). | Posted | | Median | Full Range | Hours | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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 (QD) 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 (BID); 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. |
| |
| Primary | Arm B: Time of the Maximum Observed Concentration (Tmax) | | 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). | Posted | | Median | Full Range | Hours | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| Primary | Arm A: Apparent Terminal Elimination Half-life (t1/2) | | 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). | Posted | | Geometric Mean | Full Range | Hours | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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 (QD) 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 (BID); 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. |
| |
| Primary | Arm B: Apparent Terminal Elimination Half-life (t1/2) | | 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). | Posted | | Geometric Mean | Full Range | Hours | | 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) | | | | ID | Title | Description |
|---|
| OG000 | 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. |
| |
| 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 | The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib | Posted | | Count of Participants | | Participants | | From the date of first study drug administration to 30 days after last dose (up to approximately 15 months) | | | | ID | Title | Description |
|---|
| OG000 | 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. | | OG001 | 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. |
|