Trial Outcomes & Findings for Interaction Study of Zanubrutinib With Moderate and Strong CYP3A Inhibitors in Participants With B-Cell Malignancies (NCT NCT04551963)
NCT ID: NCT04551963
Last Updated: 2024-10-26
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
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)
Results posted on
2024-10-26
Participant Flow
This study was conducted at 7 study centers in Australia.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
13
|
|
Overall Study
COMPLETED
|
11
|
12
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
1
|
|
Overall Study
Death
|
1
|
0
|
Baseline Characteristics
Interaction Study of Zanubrutinib With Moderate and Strong CYP3A Inhibitors in Participants With B-Cell Malignancies
Baseline characteristics by cohort
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 Participants
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.
|
Arm B: Zanubrutinib With or Without Strong CYP3A
n=13 Participants
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.
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70.5 Years
STANDARD_DEVIATION 9.85 • n=5 Participants
|
71.8 Years
STANDARD_DEVIATION 8.64 • n=7 Participants
|
71.1 Years
STANDARD_DEVIATION 9.10 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 Participants
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.
|
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.
|
|---|---|---|
|
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: 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 45.80
|
—
|
|
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
|
—
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 Participants
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.
|
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.
|
|---|---|---|
|
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 49.20
|
—
|
|
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 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
|
—
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=12 Participants
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.
|
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.
|
|---|---|---|
|
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: 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
|
—
|
|
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
|
—
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=12 Participants
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.
|
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.
|
|---|---|---|
|
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 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 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
|
—
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 Participants
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.
|
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.
|
|---|---|---|
|
Arm A: Maximum Observed Concentration (Cmax)
Zanubrutinib 320 mg QD
|
520.78 ng/mL
Geometric Coefficient of Variation 39.18
|
—
|
|
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: Maximum Observed Concentration (Cmax)
Zanubrutinib 80 mg BID + 180 mg diltiazem QD
|
211.06 ng/mL
Geometric Coefficient of Variation 36.59
|
—
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 Participants
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.
|
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.
|
|---|---|---|
|
Arm B: Maximum Observed Concentration (Cmax)
Zanubrutinib 320 mg QD
|
428.88 ng/mL
Geometric Coefficient of Variation 43.56
|
—
|
|
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 B: Maximum Observed Concentration (Cmax)
Zanubrutinib 80 mg QD + 250 mg clarithromycin BID
|
215.15 ng/mL
Geometric Coefficient of Variation 51.79
|
—
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 Participants
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.
|
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.
|
|---|---|---|
|
Arm A: Time of the Maximum Observed Concentration (Tmax)
Zanubrutinib 320 mg QD
|
2.03 Hours
Interval 1.0 to 4.0
|
—
|
|
Arm A: Time of the Maximum Observed Concentration (Tmax)
Zanubrutinib 80 mg BID + 400 mg fluconazole QD
|
2.93 Hours
Interval 1.0 to 4.0
|
—
|
|
Arm A: Time of the Maximum Observed Concentration (Tmax)
Zanubrutinib 80 mg BID + 180 mg diltiazem QD
|
2.05 Hours
Interval 1.0 to 4.2
|
—
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 Participants
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.
|
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.
|
|---|---|---|
|
Arm B: Time of the Maximum Observed Concentration (Tmax)
Zanubrutinib 320 mg QD
|
3.00 Hours
Interval 1.0 to 4.0
|
—
|
|
Arm B: Time of the Maximum Observed Concentration (Tmax)
Zanubrutinib 80 mg QD + 200 mg voriconazole BID
|
2.05 Hours
Interval 1.0 to 3.9
|
—
|
|
Arm B: Time of the Maximum Observed Concentration (Tmax)
Zanubrutinib 80 mg QD + 250 mg clarithromycin BID
|
2.08 Hours
Interval 0.5 to 7.9
|
—
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 Participants
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.
|
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.
|
|---|---|---|
|
Arm A: Apparent Terminal Elimination Half-life (t1/2)
Zanubrutinib 320 mg QD
|
2.15 Hours
Interval 1.4 to 4.5
|
—
|
|
Arm A: Apparent Terminal Elimination Half-life (t1/2)
Zanubrutinib 80 mg BID + 400 mg fluconazole QD
|
2.10 Hours
Interval 1.7 to 3.3
|
—
|
|
Arm A: Apparent Terminal Elimination Half-life (t1/2)
Zanubrutinib 80 mg BID + 180 mg diltiazem QD
|
2.14 Hours
Interval 1.4 to 4.0
|
—
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 Participants
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.
|
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.
|
|---|---|---|
|
Arm B: Apparent Terminal Elimination Half-life (t1/2)
Zanubrutinib 320 mg QD
|
1.79 Hours
Interval 1.2 to 2.5
|
—
|
|
Arm B: Apparent Terminal Elimination Half-life (t1/2)
Zanubrutinib 80 mg QD + 200 mg voriconazole BID
|
2.38 Hours
Interval 1.6 to 2.8
|
—
|
|
Arm B: Apparent Terminal Elimination Half-life (t1/2)
Zanubrutinib 80 mg QD + 250 mg clarithromycin BID
|
2.08 Hours
Interval 1.4 to 2.9
|
—
|
SECONDARY outcome
Timeframe: 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
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinical laboratory tests
Outcome measures
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 Participants
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.
|
Arm B: Zanubrutinib With or Without Strong CYP3A
n=13 Participants
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.
|
|---|---|---|
|
Number of Participants Experiencing Adverse Events (AEs)
At least one TEAE
|
12 Participants
|
12 Participants
|
|
Number of Participants Experiencing Adverse Events (AEs)
At least one SAE
|
3 Participants
|
1 Participants
|
Adverse Events
Arm A: Zanubrutinib With or Without Moderate CYP3A
Serious events: 3 serious events
Other events: 12 other events
Deaths: 1 deaths
Arm B: Zanubrutinib With or Without Strong CYP3A
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 participants at risk
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.
|
Arm B: Zanubrutinib With or Without Strong CYP3A
n=13 participants at risk
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.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Fall
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Injury, poisoning and procedural complications
Traumatic haemorrhage
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mantle cell lymphoma refractory
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Nervous system disorders
Radiculopathy
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Infections and infestations
Pneumonia cryptococcal
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
Other adverse events
| Measure |
Arm A: Zanubrutinib With or Without Moderate CYP3A
n=13 participants at risk
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.
|
Arm B: Zanubrutinib With or Without Strong CYP3A
n=13 participants at risk
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.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
15.4%
2/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Gastrointestinal disorders
Constipation
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
23.1%
3/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
23.1%
3/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
15.4%
2/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Injury, poisoning and procedural complications
Contusion
|
23.1%
3/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
30.8%
4/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Injury, poisoning and procedural complications
Fall
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
15.4%
2/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.4%
2/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
23.1%
3/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
15.4%
2/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
15.4%
2/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Infections and infestations
Upper respiratory tract infection
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Blood and lymphatic system disorders
Neutropenia
|
15.4%
2/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
15.4%
2/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
General disorders
Fatigue
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
15.4%
2/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
General disorders
Oedema peripheral
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
7.7%
1/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
|
Investigations
Blood creatinine increased
|
0.00%
0/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
15.4%
2/13 • From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)
The safety analysis set included all participants who were enrolled and received any dose of zanubrutinib
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER