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

B-cell Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04551963
• Other study ID #: BGB-3111-113
• Status: Completed
• Phase: Phase 1
• Start date: November 15, 2020
• Est. completion date: February 21, 2022

Study information

• Verified date: February 2023
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to assess the steady-state zanubrutinib pharmacokinetics (PK) when co-administered with moderate and strong cytochrome P450 family 3 subfamily A (CYP3A) inhibitors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 21, 2022
• Est. primary completion date: February 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Malignancies
• Neoplasms

Intervention

Drug:
• Zanubrutinib
Capsules administered at a dose and frequency as specified in the treatment arm
• Fluconazole
Capsules administered at a dose and frequency as specified in the treatment arm
• Diltiazem
Capsules administered at a dose and frequency as specified in the treatment arm
• Voriconazole
Capsules administered at a dose and frequency as specified in the treatment arm
• Clarithromycin
Capsules administered at a dose and frequency as specified in the treatment arm

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Monash Health	Clayton	Victoria
Australia	Concord General Repatriation Hospital	Concord	New South Wales
Australia	Peninsula Private Hospital	Frankston	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia
Australia	John Flynn Private Hospital	Tugun	Queensland

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

Australia, 

References & Publications (1)

Tariq B, Ou YC, Stern JC, Mundra V, Wong Doo N, Walker P, Lewis KL, Lin C, Novotny W, Sahasranaman S, Opat S. A phase 1, open-label, randomized drug-drug interaction study of zanubrutinib with moderate or strong CYP3A inhibitors in patients with B-cell ma — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Arm A: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t)		Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Primary	Arm B: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t)		Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Primary	Arm A: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h)		Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Primary	Arm B: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h)		Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Primary	Arm A: Maximum Observed Concentration (Cmax)		Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Primary	Arm B: Maximum Observed Concentration (Cmax)		Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Primary	Arm A: Time of the Maximum Observed Concentration (Tmax)		Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Primary	Arm B: Time of the Maximum Observed Concentration (Tmax)		Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Primary	Arm A: Apparent Terminal Elimination Half-life (t1/2)		Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Primary	Arm B: Apparent Terminal Elimination Half-life (t1/2)		Predose, 0.5, 1, 2, 3, 4, 6, 8 and 10 hours on Cycle 1 Day 3, Day 10, and Day 28 (30-day cycle)
Secondary	Number of Participants Experiencing Adverse Events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinical laboratory tests	From the date of first study drug administration to 30 days after last dose (up to approximately 15 months)