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

• ClinicalTrials.gov Identifier: NCT04551963
• Recruitment Status: Completed
• First Posted: September 16, 2020
• Last Update Posted: July 20, 2022
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: September 9, 2020
• First Posted Date: September 16, 2020
• Last Update Posted Date: July 20, 2022
• Actual Study Start Date: November 15, 2020
• Actual Primary Completion Date: February 21, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 15, 2020)

• 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) ]
• AUC from 0 to 24 hours (AUC0-24h) [ Time Frame: Day 3, Day 10, and Day 26 of Cycle 1 (28-day cycle) ]
• maximum plasma concentration (Cmax) [ Time Frame: Day 3, Day 10, and Day 26 of Cycle 1 (28-day cycle) ]
• time to reach the Cmax (Tmax) [ Time Frame: Day 3, Day 10, and Day 26 of Cycle 1 (28-day cycle) ]
• apparent terminal elimination half-life (t1/2) [ Time Frame: Day 3, Day 10, and Day 26 of Cycle 1 (28-day cycle) ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 15, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Interaction Study of Zanubrutinib With Moderate and Strong CYP3A Inhibitors in Participants With B-Cell Malignancies
• Official Title: A Drug-Drug Interaction Study of Zanubrutinib With Moderate and Strong CYP3A Inhibitors in Patients With B-Cell Malignancies
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: B-cell Malignancies

Intervention

• 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)
• Drug: Voriconazole
  200 mg capsules administered twice daily (BID)
• Drug: Clarithromycin
  250 mg capsules administered twice daily (BID)

Study Arms

• 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
  Interventions:

  • Drug: Zanubrutinib
  • Drug: Fluconazole
  • Drug: Diltiazem
• 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
  Interventions:

  • Drug: Zanubrutinib
  • Drug: Voriconazole
  • Drug: Clarithromycin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 18, 2022): 26
• Original Estimated Enrollment (submitted: September 15, 2020): 30
• Actual Study Completion Date: February 21, 2022
• Actual Primary Completion Date: February 21, 2022 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT04551963
• Other Study ID Numbers: BGB-3111-113
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: BeiGene
• Original Responsible Party: Same as current
• Current Study Sponsor: BeiGene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; BeiGene

• PRS Account: BeiGene
• Verification Date: July 2022