CompletedPhase 1

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

Australia26 participantsStarted 2020-11-15

Plain-language 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.

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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.

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.

What they're measuring

Arm A: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t)

Timeframe: 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)

Arm B: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t)

Timeframe: 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)

Arm A: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h)

Timeframe: 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)

Arm B: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h)

Timeframe: 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)

Arm A: Maximum Observed Concentration (Cmax)

Timeframe: 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)

Arm B: Maximum Observed Concentration (Cmax)

Timeframe: 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)

Trial details

NCT IDNCT04551963

SponsorBeiGene

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2022-02-21

Results submitted2023-02-17

View on ClinicalTrials.gov More B-cell Malignancies trials

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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.

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.