Absolute Bioavailability and Pharmacokinetic Comparability of Sirukumab Following Subcutaneous Administration by a Prefilled Syringe or an Autoinjector

摘要

This phase 1, randomized, open-label study assessed the absolute bioavailability and pharmacokinetic comparability of sirukumab, a human anti-interleukin-6 monoclonal antibody, following subcutaneous (SC) administration via Prefilled Syringe-UltraSafe Passive (R) Delivery System (PFS-U) or Prefilled Syringe-SmartJect (R) Autoinjector (PFS-AI; Janssen Research & Development, LLC, Spring House, Pennsylvania). A total of 144 healthy male subjects were randomized to 5 single-dose treatment groups: sirukumab 50 mg and 100 mg (each by PFS-U and PFS-AI) and sirukumab 100 mg intravenous (IV) infusion. Pharmacokinetic parameters were calculated using noncompartmental analysis. Following SC administration, maximum serum concentrations (C-max) and area under the concentration-vs-time curve (AUC) increased in an approximately dose-proportional manner. Median time to reach C-max was 5 days, and mean half-life ranged from 16 to 19 days. Mean absolute bioavailability of sirukumab by PFS-AI and PFS-U, respectively, was estimated at 92.4% and 81.4% with 100 mg and 88.4% and 94.7% with 50 mg. Ratios of geometric means (90% confidence intervals) of C-max and AUC(0-77d) for PFS-AI: PFS-U were 1.13 (1.03, 1.25) and 1.14 (1.05, 1.24), respectively, indicating comparable systemic exposures of sirukumab following a single 100-mg SC dose by PFS-U or PFS-AI. The incidence of antibodies to sirukumab was low (1.4%). No new safety concerns associated with sirukumab were identified at either dose.