Trial Outcomes & Findings for The Effect of Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of Zanubrutinib in Healthy Males (NCT NCT04470908)
NCT ID: NCT04470908
Last Updated: 2024-10-26
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
13 participants
Primary outcome timeframe
Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Results posted on
2024-10-26
Participant Flow
This was a single-center study with dosing in a fixed sequence. A total of 13 participants were enrolled and 12 completed the study.
Participant milestones
| Measure |
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
|
|---|---|
|
Zanubrutinib on Day 1
STARTED
|
13
|
|
Zanubrutinib on Day 1
COMPLETED
|
13
|
|
Zanubrutinib on Day 1
NOT COMPLETED
|
0
|
|
Rifabutin on Days 3 to 10
STARTED
|
13
|
|
Rifabutin on Days 3 to 10
COMPLETED
|
13
|
|
Rifabutin on Days 3 to 10
NOT COMPLETED
|
0
|
|
Zanubrutinib + Rifabutin on Day 11
STARTED
|
13
|
|
Zanubrutinib + Rifabutin on Day 11
COMPLETED
|
12
|
|
Zanubrutinib + Rifabutin on Day 11
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
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
|
|---|---|
|
Zanubrutinib + Rifabutin on Day 11
Lost to Follow-up
|
1
|
Baseline Characteristics
The Effect of Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of Zanubrutinib in Healthy Males
Baseline characteristics by cohort
| Measure |
Zanubrutinib + Rifabutin
n=13 Participants
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
|
|---|---|
|
Age, Continuous
|
48.8 Years
STANDARD_DEVIATION 11.00 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11Population: 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).
Outcome measures
| Measure |
Zanubrutinib
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 (reference)
|
Zanubrutinib + Rifabutin
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 and after co-administration with oral rifabutin 300 mg on Day 11 (test)
|
Zanubrutinib + Rifabutin on Day 11
Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11
|
|---|---|---|---|
|
Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Zanubrutinib
|
2700 h*ng/mL
Geometric Coefficient of Variation 24.8
|
1530 h*ng/mL
Geometric Coefficient of Variation 21.4
|
—
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11Population: 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).
Outcome measures
| Measure |
Zanubrutinib
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 (reference)
|
Zanubrutinib + Rifabutin
n=12 Participants
Single oral dose zanubrutinib 320 mg on Day 1 and after co-administration with oral rifabutin 300 mg on Day 11 (test)
|
Zanubrutinib + Rifabutin on Day 11
Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11
|
|---|---|---|---|
|
AUC From Time Zero to Infinity (AUC0-∞) of Zanubrutinib
|
2780 h*ng/mL
Geometric Coefficient of Variation 23.3
|
1590 h*ng/mL
Geometric Coefficient of Variation 22.2
|
—
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11Population: 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).
Outcome measures
| Measure |
Zanubrutinib
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 (reference)
|
Zanubrutinib + Rifabutin
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 and after co-administration with oral rifabutin 300 mg on Day 11 (test)
|
Zanubrutinib + Rifabutin on Day 11
Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Zanubrutinib
|
489 ng/mL
Geometric Coefficient of Variation 38.1
|
253 ng/mL
Geometric Coefficient of Variation 33.7
|
—
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11Population: 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).
Outcome measures
| Measure |
Zanubrutinib
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 (reference)
|
Zanubrutinib + Rifabutin
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 and after co-administration with oral rifabutin 300 mg on Day 11 (test)
|
Zanubrutinib + Rifabutin on Day 11
Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11
|
|---|---|---|---|
|
Time to the Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib
|
1.50 Hours
Interval 1.0 to 4.02
|
2.00 Hours
Interval 1.0 to 8.0
|
—
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11Population: 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).
Outcome measures
| Measure |
Zanubrutinib
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 (reference)
|
Zanubrutinib + Rifabutin
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 and after co-administration with oral rifabutin 300 mg on Day 11 (test)
|
Zanubrutinib + Rifabutin on Day 11
Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11
|
|---|---|---|---|
|
Time of the Last Quantifiable Concentration (Tlast) of Zanubrutinib
|
36.0 Hours
Interval 24.0 to 36.0
|
36.0 Hours
Interval 24.0 to 36.0
|
—
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11Population: 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).
Outcome measures
| Measure |
Zanubrutinib
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 (reference)
|
Zanubrutinib + Rifabutin
n=12 Participants
Single oral dose zanubrutinib 320 mg on Day 1 and after co-administration with oral rifabutin 300 mg on Day 11 (test)
|
Zanubrutinib + Rifabutin on Day 11
Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11
|
|---|---|---|---|
|
Apparent Terminal Elimination Half-life (t1/2) of Zanubrutinib
|
7.24 Hours
Standard Deviation 3.10
|
7.00 Hours
Standard Deviation 4.46
|
—
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11Population: 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).
Outcome measures
| Measure |
Zanubrutinib
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 (reference)
|
Zanubrutinib + Rifabutin
n=12 Participants
Single oral dose zanubrutinib 320 mg on Day 1 and after co-administration with oral rifabutin 300 mg on Day 11 (test)
|
Zanubrutinib + Rifabutin on Day 11
Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11
|
|---|---|---|---|
|
Apparent Oral Clearance (CL/F) of Zanubrutinib
|
115 Liters/hour
Geometric Coefficient of Variation 23.3
|
201 Liters/hour
Geometric Coefficient of Variation 22.2
|
—
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11Population: 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).
Outcome measures
| Measure |
Zanubrutinib
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 (reference)
|
Zanubrutinib + Rifabutin
n=12 Participants
Single oral dose zanubrutinib 320 mg on Day 1 and after co-administration with oral rifabutin 300 mg on Day 11 (test)
|
Zanubrutinib + Rifabutin on Day 11
Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11
|
|---|---|---|---|
|
Apparent Volume of Distribution (Vz/F) of Zanubrutinib
|
1080 Liters
Geometric Coefficient of Variation 68.4
|
1750 Liters
Geometric Coefficient of Variation 70.9
|
—
|
SECONDARY outcome
Timeframe: From the date of first study drug administration to 30 days after last dose (up to 3.5 months)Population: The safety population included all participants who received at least 1 dose of zanubrutinib.
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
Outcome measures
| Measure |
Zanubrutinib
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 (reference)
|
Zanubrutinib + Rifabutin
n=13 Participants
Single oral dose zanubrutinib 320 mg on Day 1 and after co-administration with oral rifabutin 300 mg on Day 11 (test)
|
Zanubrutinib + Rifabutin on Day 11
n=13 Participants
Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11
|
|---|---|---|---|
|
Number of Participants Experiencing Adverse Events (AEs)
At least 1 treatment-emergent adverse event (TEAE)
|
1 Participants
|
6 Participants
|
0 Participants
|
|
Number of Participants Experiencing Adverse Events (AEs)
Serious adverse events
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Experiencing Adverse Events (AEs)
Laboratory-related TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Experiencing Adverse Events (AEs)
Vital sign TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Experiencing Adverse Events (AEs)
Physical examination TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Experiencing Adverse Events (AEs)
Electrocardiogram TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Zanubrutinib on Day 1
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Rifabutin on Days 3 to 10
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Zanubrutinib + Rifabutin on Day 11
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Zanubrutinib on Day 1
n=13 participants at risk
Single oral dose zanubrutinib 320 mg on Day 1
|
Rifabutin on Days 3 to 10
n=13 participants at risk
Once daily oral rifabutin 300 mg on Days 3 to 10
|
Zanubrutinib + Rifabutin on Day 11
n=13 participants at risk
Single oral dose zanubrutinib 320 mg and once daily oral rifabutin 300 mg on Day 11
|
|---|---|---|---|
|
Renal and urinary disorders
Chromaturia
|
0.00%
0/13 • 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
|
46.2%
6/13 • Number of events 6 • 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
|
0.00%
0/13 • 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
|
|
General disorders
Vessel puncture site haematoma
|
7.7%
1/13 • Number of events 1 • 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
|
0.00%
0/13 • 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
|
0.00%
0/13 • 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
|
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