title: Safety, tolerability and pharmacokinetics of a human anti-interleukin-13 monoclonal antibody (CNTO 5825) in an ascending single-dose first-in-human study.
abstract: OBJECTIVE
  To assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of CNTO 5825 following single-dose intravenous (i.v.) and subcutaneous (s.c.) administration in healthy and healthy atopic subjects.
  
  
  METHODS
  Sixty-four subjects received a single dose of placebo or CNTO 5825 (0.1, 0.3, 1.0, 3.0, or 10 mg kg(-1) i.v. in a dose-escalating manner, or 3.0 mg kg(-1) s.c. in healthy subjects; and 10 mg kg(-1) i.v. in healthy atopic subjects). Subjects were observed for 96 h postadministration and followed for 16 weeks. Safety and tolerability were monitored, and serum samples were collected to measure CNTO 5825 concentrations, antibodies to CNTO 5825 and PD biomarkers.
  
  
  RESULTS
  Most adverse events were mild to moderate in severity and considered to be unrelated to CNTO 5825, with no dose-dependent trends seen. The two serious adverse events were considered to be unrelated to CNTO 5825. After i.v. administration, CNTO 5825 exhibited linear PK, with a terminal half-life of ∼22-32 days. After a single 3 mg kg(-1) s.c. dose in healthy subjects, CNTO 5825 was absorbed into the systemic circulation with a median time to maximum serum concentration (tmax) of 5.45 days and absolute bioavailability of ∼75%. The PK profile of CNTO 5825 at 10 mg kg(-1) was similar in both healthy and healthy atopic subjects. No antibodies to CNTO 5825 were detected through week 16. In the CNTO 5825-treated healthy atopic subjects, there was a significant reduction in serum IgE and C-C motif chemokine ligand 17 (P = 0.028 and 0.068 vs. placebo, respectively).
  
  
  CONCLUSIONS
  CNTO 5825 was well tolerated, had an acceptable safety profile, exhibited linear PK characteristics, and no detected antibodies to CNTO 5825.
authors.affiliation: Immunology Translational Medicine, Janssen Research & Development, LLC, Spring House, PA 19477, USA.
authors.forename: Bart
authors.initials: B
authors.lastname: van Hartingsveldt
authors.forename: Ivo P
authors.initials: IP
authors.lastname: Nnane
authors.forename: Esther
authors.initials: E
authors.lastname: Bouman-Thio
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Loza
authors.forename: Alexa
authors.initials: A
authors.lastname: Piantone
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Davis
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Petty
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D018793:Interleukin-13 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C000608264:CNTO 5825; D018793:Interleukin-13