title: Pharmacokinetics and safety of golimumab in healthy Chinese subjects following a single subcutaneous administration in a randomized phase I trial.
abstract: OBJECTIVE
  Golimumab is an anti-tumor necrosis factor-α human immunoglobulin G1κ monoclonal antibody that is efficacious for the treatment of moderate to severe rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis in adults. The objective of this study was to assess the pharmacokinetic characteristics of golimumab in healthy male Chinese subjects following a single subcutaneous (SC) administration of golimumab 50 or 100 mg. The safety, tolerability, and immunogenicity of a single SC administration of golimumab in Chinese subjects were also evaluated.
  
  
  METHODS
  This was a phase I, randomized, open-label, single-dose, single-period, single-center study. Twenty-four healthy male Chinese subjects were randomized (1:1) to receive a single SC administration of golimumab 50 or 100 mg. Serial blood samples for the measurement of serum golimumab concentrations were collected and analyzed using a validated electrochemiluminescent immunoassay method. The pharmacokinetic parameters [maximum observed serum concentration (C(max)), time to reach C(max) (t(max)), area under the serum concentration-time curve from time zero to infinity (AUC∞), and terminal half-life (t(½))] of golimumab were derived using a noncompartmental analysis.
  
  
  RESULTS
  Following a single SC administration of golimumab 50 or 100 mg in Chinese male subjects (age 19-41 years, body weight 60-76 kg), mean ± standard deviation C(max) (3.6 ± 1.6 and 7.5 ± 1.4 μg/mL, respectively) and AUC∞ (59.8 ± 19.8 and 132.8 ± 27.0 μg·day/mL, respectively) increased in a dose-proportional manner. The median t(max) was in the range of 4.5-5.0 days, and the mean t(½) was in the range of 10.8-11.9 days. Among 24 subjects, 23 had appropriate samples for evaluation of antibodies to golimumab, and one subject (1/23, 4.3%) in the 100-mg group tested positive. Three mild adverse events were reported (infected sebaceous cyst, upper respiratory tract infection, and headache), all in the 50-mg group; none were considered to be related to the study agent.
  
  
  CONCLUSIONS
  Golimumab exhibited linear pharmacokinetics at dose levels of 50 and 100 mg following a single SC administration in healthy Chinese subjects. Single SC administrations of golimumab 50 or 100 mg were considered to be generally well tolerated. The results from this study indicate that there are no apparent ethnic differences in the pharmacokinetics of golimumab between Chinese and Caucasian subjects.
authors: Biologics Clinical Pharmacology, Janssen Research & Development, LLC, Welsh and McKean Road, Spring House, PA, 19477, USA.
authors: Yanli
authors: Y
authors: Zhuang
authors: Sally
authors: S
authors: Lyn
authors: Yuan
authors: Y
authors: Lv
authors: Zhenhua
authors: Z
authors: Xu
authors: Esther
authors: E
authors: Bouman-Thio
authors: Tara
authors: T
authors: Masterson
authors: Joyce A
authors: JA
authors: Ford
authors: Monica
authors: M
authors: Keen
authors: Kevin J
authors: KJ
authors: Petty
authors: Hugh M
authors: HM
authors: Davis
authors: Honghui
authors: H
authors: Zhou
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002681:China; D006801:Humans; D055103:Hypodermoclysis
chemical_list: D000911:Antibodies, Monoclonal; C529000:golimumab
references: Clin Ther. 2012 Jan;34(1):77-90
references: 22169051
references: Drug Discov Today. 2006 Jan;11(1-2):81-8
references: 16478695
references: J Clin Pharmacol. 2010 Jul;50(7):792-802
references: 20133508
references: Ann Rheum Dis. 2010 Jun;69(6):1129-35
references: 20444749
references: Ann Rheum Dis. 2009 Jun;68(6):789-96
references: 19066176
references: Arthritis Rheum. 2009 Apr;60(4):976-86
references: 19333944
references: Arthritis Rheum. 2009 Aug;60(8):2272-83
references: 19644849
references: Arthritis Rheum. 2008 Nov;58(11):3402-12
references: 18975305
references: J Clin Pharmacol. 2012 Aug;52(8):1273-6
references: 22135052
references: J Clin Pharmacol. 2010 Mar;50(3):276-84
references: 19940229
references: Lancet. 2009 Jul 18;374(9685):210-21
references: 19560810
references: J Clin Pharmacol. 2007 Mar;47(3):383-96
references: 17322150