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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04551963
Recruitment Status : Completed
First Posted : September 16, 2020
Last Update Posted : July 20, 2022
Sponsor:
Information provided by (Responsible Party):
BeiGene

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
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 : November 15, 2020
Actual Primary Completion Date : February 21, 2022
Actual Study Completion Date : February 21, 2022

Resource links provided by the National Library of Medicine


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

Secondary Outcome Measures :
  1. Number of participants experiencing Adverse Events (AEs) [ Time Frame: Up to 6 28-day cycles ]
  2. Number of participants experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 6 28-day cycles ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Histologically or cytologically confirmed CLL/SLL, MCL, WM, or MZL.
  2. 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.
  3. Baseline Eastern Cooperative Oncology Group performance status of 0 to 1.
  4. Meet protocol guidelines for adequate bone marrow, kidney, liver, and cardiac function.

Key Exclusion Criteria:

  1. 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.
  2. History of stroke or intracranial hemorrhage (within 6 months of treatment start).
  3. Known hypersensitivity or contraindication to zanubrutinib, diltiazem, clarithromycin, fluconazole, or voriconazole.
  4. Prior exposure to zanubrutinib or other Bruton tyrosine kinase inhibitor
  5. 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04551963


Locations
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Australia, New South Wales
Concord General Repatriation Hospital
Concord, New South Wales, Australia, 2139
Australia, Queensland
John Flynn Private Hospital
Tugun, Queensland, Australia, 4224
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Flinders Medical Centre
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Monash Health
Clayton, Victoria, Australia, 3168
Peninsula Private Hospital
Frankston, Victoria, Australia, 3199
Australia, Western Australia
Linear Clinical Research
Nedlands, Western Australia, Australia, 6009
Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Study Director BeiGene
More Information
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT04551963    
Other Study ID Numbers: BGB-3111-113
First Posted: September 16, 2020    Key Record Dates
Last Update Posted: July 20, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Neoplasms
Clarithromycin
Fluconazole
Voriconazole
Zanubrutinib
Diltiazem
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antifungal Agents
 14-alpha Demethylase Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Vasodilator Agents
Antineoplastic Agents
Protein Kinase Inhibitors