The Effect of Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of Zanubrutinib in Healthy Males

A Phase 1, Open-label, Fixed-sequence Study to Investigate the Effect of the Moderate CYP3A Inducer Rifabutin on the Pharmacokinetics of Zanubrutinib in Healthy Male Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04470908

Enrollment

Registered

2020-07-14

Start date

2020-07-29

Completion date

2020-11-10

Last updated

2024-10-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy, Male

Keywords

Phase 1, Healthy volunteers, Pharmacokinetics

Brief summary

The primary objective of this study was to determine the effect of the moderate cytochrome P450 3A (CYP3A) inducer rifabutin on the pharmacokinetics (PK) of zanubrutinib in healthy males.

Interventions

DRUGZanubrutinib

Single oral dose of 320 mg

DRUGRifabutin

Oral dose of 300 mg once daily

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

Key Inclusion Criteria: 1. Males of any race, between 18 and 65 years of age, inclusive. 2. Male participants in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening 3. Must have a body mass index (BMI) between 18 and 32 kg/m\^2 Key

Exclusion criteria

1. Participants with a clinically relevant history or presence of any clinically significant disease 2. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed) 3. History of drug or alcohol abuse within 1 year prior to check-in 4. Use or intended use of any nonprescription medications/products including vitamins, minerals, herbal/plant-derived preparations within 7 days prior to check-in 5. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result and/or a positive human immunodeficiency virus (HIV) at screening 6. Use of tobacco- or nicotine-containing products within 3 months prior to check-in 7. Use or intended use of any prescription medications/products within 14 days prior to check-in NOTE: Other protocol defined Inclusion/

Design outcomes

Primary

Measure	Time frame
Apparent Volume of Distribution (Vz/F) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Maximum Observed Plasma Concentration (Cmax) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
AUC From Time Zero to Infinity (AUC0-∞) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Time to the Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Time of the Last Quantifiable Concentration (Tlast) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Terminal Elimination Half-life (t1/2) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11
Apparent Oral Clearance (CL/F) of Zanubrutinib	Predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 hours postdose on Days 1 and 11

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 3.5 months)	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

Countries

United States

Participant flow

Recruitment details

This was a single-center study with dosing in a fixed sequence. A total of 13 participants were enrolled and 12 completed the study.

Participants by arm

Arm	Count
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	13
Total	13

Withdrawals & dropouts

Period	Reason	FG000
Zanubrutinib + Rifabutin on Day 11	Lost to Follow-up	1

Baseline characteristics

Characteristic	Zanubrutinib + Rifabutin
Age, Continuous	48.8 Years STANDARD_DEVIATION 11
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	12 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	13 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 13	0 / 13	0 / 13
other Total, other adverse events	1 / 13	6 / 13	0 / 13
serious Total, serious adverse events	0 / 13	0 / 13	0 / 13