title: Absolute Bioavailability and Pharmacokinetic Comparability of Sirukumab Following Subcutaneous Administration by a Prefilled Syringe or an Autoinjector.
abstract: 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® Delivery System (PFS-U) or Prefilled Syringe-SmartJect® 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 (Cmax) and area under the concentration-vs-time curve (AUC) increased in an approximately dose-proportional manner. Median time to reach Cmaxwas 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 Cmaxand AUC0-77dfor 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.
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Janssen Biologics BV, Leiden, The Netherlands.
authors.forename: D E
authors.initials: DE
authors.lastname: de Vries
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Marciniak
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Davis
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Leon
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Raible
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D013594:Syringes; D013997:Time Factors; D055815:Young Adult; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000093242:Interleukin-6 Inhibitors; C568922:sirukumab
keywords: autoinjector; comparability; pharmacokinetics; sirukumab; subcutaneous administration