Abstract
Background and Objectives
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 (Cmax), time to reach Cmax (tmax), area under the serum concentration-time curve from time zero to infinity (AUC∞), and terminal half-life (t½)] 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 Cmax (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 tmax was in the range of 4.5–5.0 days, and the mean t½ 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.
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References
Emery P, Fleischmann RM, Moreland LW, Hsia EC, Strusberg I, Durez P, et al. Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum. 2009;60(8):2272–83.
Keystone EC, Genovese MC, Klareskog L, Hsia EC, Hall ST, Miranda PC, et al. Golimumab, a human antibody to tumour necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis. 2009;68(6):789–96.
Smolen JS, Kay J, Doyle MK, Landewe R, Matteson EL, Wollenhaupt J, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009;374(9685):210–21.
Kavanaugh A, McInnes I, Mease P, Krueger GG, Gladman D, Gomez-Reino J, et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum. 2009;60(4):976–86.
Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008;58(11):3402–12.
Keystone E, Genovese MC, Klareskog L, Hsia EC, Hall S, Miranda PC, et al. Golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: 52-week results of the GO-FORWARD study. Ann Rheum Dis. 2010;69(6):1129–35.
Zhou H, Jang H, Fleischmann RM, Bouman-Thio E, Xu Z, Marini JC, et al. Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis. J Clin Pharmacol. 2007;47(3):383–96.
Xu Z, Wang Q, Zhuang Y, Frederick B, Yan H, Bouman-Thio E, et al. Subcutaneous bioavailability of golimumab at 3 different injection sites in healthy subjects. J Clin Pharmacol. 2010;50(3):276–84.
Ling J, Lyn S, Xu Z, Achira M, Bouman-Thio E, Shishido A, et al. Lack of racial differences in the pharmacokinetics of subcutaneous golimumab in healthy Japanese and Caucasian male subjects. J Clin Pharmacol. 2010;50(7):792–802.
Zhuang Y, Xu Z, Frederick B, de Vries DE, Ford JA, Keen M, et al. Golimumab pharmacokinetics after repeated subcutaneous and intravenous administrations in patients with rheumatoid arthritis and the effect of concomitant methotrexate: an open-label, randomized study. Clin Ther. 2012;34(1):77–90.
Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. New York: Marcel Dekker; 1982.
Tabrizi MA, Tseng CM, Roskos LK. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006;11(1–2):81–8.
Zhou H, Tsukamoto Y, Davis HM. Should clinical pharmacokinetic bridging studies between Caucasian and Asian populations be required for approval of monoclonal antibodies? J Clin Pharmacol. 2012;52(8):1273–6.
Simponi: package insert. Horsham: Janssen Biotech, Inc.; 2013.
Acknowledgments
Authors YZ, SL, ZX, EB-T, TM, JAF, MK, KJP, HMD, and HZ are or were employees of the study sponsor, Janssen Research & Development, LLC. at the time this work was performed and own/owned stock in Johnson & Johnson. EB-T is currently employed at DePuy Orthopaedics, Inc. Author YL is an employee of Peking University First Hospital, which received support from Janssen Research & Development, LLC. for this trial. Employees of the study sponsor, Janssen Research & Development, LLC., participated in designing the study; collecting, analyzing, and interpreting the data; and drafting the manuscript. Additional writing support was provided by employees of Janssen Biotech, Inc. All authors approved the final version for submission.
The authors thank Rebecca Clemente, PhD, and Mary Whitman, PhD, of Janssen Biotech, Inc., for editorial support.
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Zhuang, Y., Lyn, S., Lv, Y. et al. Pharmacokinetics and Safety of Golimumab in Healthy Chinese Subjects Following a Single Subcutaneous Administration in a Randomized Phase I Trial. Clin Drug Investig 33, 795–800 (2013). https://doi.org/10.1007/s40261-013-0124-7
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DOI: https://doi.org/10.1007/s40261-013-0124-7