Interaction Study of Zanubrutinib With Moderate and Strong CYP3A Inhibitors in Participants With B-Cell Malignancies

Sponsor

BeiGene (Industry)

Overall Status

Completed

CT.gov ID

NCT04551963

Collaborator

(none)

Enrollment

Locations

Arms

15.2

Actual Duration (Months)

3.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the steady-state zanubrutinib pharmacokinetics (PK) when coadministered with moderate and strong cytochrome P450 A (CYP3A) inhibitors.

Condition or Disease	Intervention/Treatment	Phase
B-cell Malignancies	Drug: Zanubrutinib Drug: Fluconazole Drug: Diltiazem Drug: Voriconazole Drug: Clarithromycin	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Drug-Drug Interaction Study of Zanubrutinib With Moderate and Strong CYP3A Inhibitors in Patients With B-Cell Malignancies

Actual Study Start Date :

Nov 15, 2020

Actual Primary Completion Date :

Feb 21, 2022

Actual Study Completion Date :

Feb 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zanubrutinib + Moderate CYP3A Cycle 1 (28 days): Zanubrutinib 80 mg twice daily (BID) + fluconazole (days 4 - 10), zanubrutinib 320 mg once daily (QD) (days 13 - 19), zanubrutinib 80 mg BID + diltiazem (days 20 - 26) Cycles 2 - 6 (28 days each): zanubrutinib 160 mg BID or 320 mg QD	Drug: Zanubrutinib 80 mg capsules administered at a dose and frequency as specified in the treatment arm Other Names: BGB-3111 BRUKINSA Drug: Fluconazole 400 mg administered as 2 x 200 mg capsules once daily (QD) Drug: Diltiazem 180 mg capsule administered once daily (QD)
Experimental: Zanubrutinib + Strong CYP3A Cycle 1 (28 days): Zanubrutinib 80 mg QD + voriconazole (days 4 - 10), zanubrutinib 320 mg QD (days 13 - 19), zanubrutinib 80 mg QD + clarithromycin (days 20 - 26) Cycles 2 - 6 (28 days each): zanubrutinib 160 mg BID or 320 mg QD	Drug: Zanubrutinib 80 mg capsules administered at a dose and frequency as specified in the treatment arm Other Names: BGB-3111 BRUKINSA Drug: Voriconazole 200 mg capsules administered twice daily (BID) Drug: Clarithromycin 250 mg capsules administered twice daily (BID)

Arm

Intervention/Treatment

Experimental: Zanubrutinib + Moderate CYP3A

Cycle 1 (28 days): Zanubrutinib 80 mg twice daily (BID) + fluconazole (days 4 - 10), zanubrutinib 320 mg once daily (QD) (days 13 - 19), zanubrutinib 80 mg BID + diltiazem (days 20 - 26) Cycles 2 - 6 (28 days each): zanubrutinib 160 mg BID or 320 mg QD

Drug: Zanubrutinib

80 mg capsules administered at a dose and frequency as specified in the treatment arm

Other Names:

BGB-3111

BRUKINSA

Drug: Fluconazole

400 mg administered as 2 x 200 mg capsules once daily (QD)

Drug: Diltiazem

180 mg capsule administered once daily (QD)

Experimental: Zanubrutinib + Strong CYP3A

Cycle 1 (28 days): Zanubrutinib 80 mg QD + voriconazole (days 4 - 10), zanubrutinib 320 mg QD (days 13 - 19), zanubrutinib 80 mg QD + clarithromycin (days 20 - 26) Cycles 2 - 6 (28 days each): zanubrutinib 160 mg BID or 320 mg QD

Drug: Zanubrutinib

80 mg capsules administered at a dose and frequency as specified in the treatment arm

Other Names:

BGB-3111

BRUKINSA

Drug: Voriconazole

200 mg capsules administered twice daily (BID)

Drug: Clarithromycin

250 mg capsules administered twice daily (BID)

Outcome Measures

Primary Outcome Measures

area under plasma concentration-time curve up to the last measurable concentration (AUC0-t) [Day 3, Day 10, and Day 26 of Cycle 1 (28-day cycle)]
AUC from 0 to 24 hours (AUC0-24h) [Day 3, Day 10, and Day 26 of Cycle 1 (28-day cycle)]
maximum plasma concentration (Cmax) [Day 3, Day 10, and Day 26 of Cycle 1 (28-day cycle)]
time to reach the Cmax (Tmax) [Day 3, Day 10, and Day 26 of Cycle 1 (28-day cycle)]
apparent terminal elimination half-life (t1/2) [Day 3, Day 10, and Day 26 of Cycle 1 (28-day cycle)]

Secondary Outcome Measures

Number of participants experiencing Adverse Events (AEs) [Up to 6 28-day cycles]
Number of participants experiencing Serious Adverse Events (SAEs) [Up to 6 28-day cycles]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Histologically or cytologically confirmed CLL/SLL, MCL, WM, or MZL.
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.
Baseline Eastern Cooperative Oncology Group performance status of 0 to 1.
Meet protocol guidelines for adequate bone marrow, kidney, liver, and cardiac function.

Key Exclusion Criteria:

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.
History of stroke or intracranial hemorrhage (within 6 months of treatment start).
Known hypersensitivity or contraindication to zanubrutinib, diltiazem, clarithromycin, fluconazole, or voriconazole.
Prior exposure to zanubrutinib or other Bruton tyrosine kinase inhibitor
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/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Concord General Repatriation Hospital	Concord	New South Wales	Australia	2139
2	John Flynn Private Hospital	Tugun	Queensland	Australia	4224
3	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
4	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
5	Monash Health	Clayton	Victoria	Australia	3168
6	Peninsula Private Hospital	Frankston	Victoria	Australia	3199
7	Linear Clinical Research	Nedlands	Western Australia	Australia	6009