A drug–drug interaction study of ibrutinib with moderate/strong CYP3A inhibitors in patients with B-cell malignancies

Abstract

This was an open-label, multicenter, phase-1 study to evaluate the drug interaction between steady-state ibrutinib and moderate (erythromycin) and strong (voriconazole) CYP3A inhibitors in patients with B-cell malignancies and to confirm dosing recommendations. During cycle 1, patients received oral ibrutinib 560 mg qd alone (Days 1–4 and 14–18), and ibrutinib 140 mg (Days 5–13; 19–27) plus erythromycin 500 mg tid (Days 5–11) and voriconazole 200 mg bid (Days 19–25). Twenty-six patients (median [range] age: 64.5 [50–88] years) were enrolled. Geometric mean ratio (90% confidence intervals) after co-administration of ibrutinib 140 mg with erythromycin and voriconazole was 74.7 (53.97–103.51) and 143.3 (107.77–190.42), respectively, versus ibrutinib 560 mg alone. The most common (≥20%) adverse events were diarrhea (27%) and neutropenia (23%). The results demonstrate that ibrutinib 140 mg with voriconazole or erythromycin provides exposure within the clinical range for patients with B-cell malignancies.

Keywords:

• Erythromycin
• CYP3A
• ibrutinib
• pharmacokinetics
• voriconazole

Acknowledgment

Authors thank all the patients for their participation in this study, Mike Huang (Janssen Research & Development, LLC) for providing valuable bioanalytical and data management support, Ashwini Patil, MS, ISMPP CMPP™ (Tata Consultancy Services, India) for medical writing assistance and Namit Ghildyal, PhD (Janssen Research & Development, LLC) for additional editorial support for this manuscript.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1460474.

Additional information

Funding

This study was sponsored by Janssen Research & Development, LLC, New Jersey, USA.