Phase 1
Completed N=26
Interaction Study of Zanubrutinib With Moderate and Strong CYP3A Inhibitors in Participants With B-Cell Malignancies
Source: ClinicalTrials.gov NCT04551963 ↗Enrolled (actual)
26
Serious AEs
15.4%
Results posted
Nov 2023
Primary outcomePrimary: Arm A: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) — 1899.32; 921.63; 797.87 h*ng/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Arm A: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) |
1899.32; 921.63; 797.87 | — |
| PRIMARY Arm B: Area Under Plasma Concentration-time Curve up to the Last Measurable Concentration (AUC0-t) |
1550.40; 1254.29; 763.00 | — |
| PRIMARY Arm A: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) |
2035.32; 1911.93; 1653.07 | — |
| PRIMARY Arm B: Area Under Plasma Concentration-time Curve From Time 0 Extrapolated to 24 Hours (AUC0-24h) |
1578.12; 1376.02; 766.71 | — |
| PRIMARY Arm A: Maximum Observed Concentration (Cmax) |
520.78; 235.72; 211.06 | — |
| PRIMARY Arm B: Maximum Observed Concentration (Cmax) |
428.88; 353.11; 215.15 | — |
| PRIMARY Arm A: Time of the Maximum Observed Concentration (Tmax) |
2.03; 2.93; 2.05 | — |
| PRIMARY Arm B: Time of the Maximum Observed Concentration (Tmax) |
3.00; 2.05; 2.08 | — |
| PRIMARY Arm A: Apparent Terminal Elimination Half-life (t1/2) |
2.15; 2.10; 2.14 | — |
| PRIMARY Arm B: Apparent Terminal Elimination Half-life (t1/2) |
1.79; 2.38; 2.08 | — |
| SECONDARY Number of Participants Experiencing Adverse Events (AEs) |
12; 12; 3; 1 | — |
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT04551963). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.