Abstract
Aim:
To evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and primary tolerability of an anti-CD11a monoclonal antibody (CMAB001) in Chinese healthy volunteers and psoriatic patients.
Methods:
Two open-label studies were conducted. One was a parallel-group, single-center, dose-escalation test, including 24 healthy adult volunteers from 18 to 45 years in age. All subjects randomly received a single subcutaneous injection dose of 0.5, 1.0 or 2.0 mg/kg. The other was a multiple-dose study: 10 adult psoriatic patients were administered weekly subcutaneous injections of 1.0 mg/kg for 7 weeks.
Results:
CMAB001 was well tolerated in the single- and multiple-dose studies. Slow absorption was observed in both studies. In the single-dose study, the concentration of CMAB001 reached its highest level 2 d later after the injection, and the Cmax increased in an approximate dose-proportionate manner, while the area under curve (AUC) showed much greater than dose-proportionate increase. In the multiple-dose study, the steady-state serum concentration level was attained following the 4th injection.
Conclusion:
CMAB001 exhibited a nonlinear pharmacokinetic profile over the dose range from 0.5 to 2.0 mg/kg, and was well tolerated in healthy volunteers and psoriatic patients.
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Acknowledgements
This project was supported by the National Natural Science Foundation of China, Shanghai Commission of Science & Technology, Ministry of Science and Technology of China (973 & 863 Program Projects), National Key projects for New Drug Development and Manufacture, Shanghai Pudong Commission of Science & Technology and Shanghai Leading Academic Discipline Project (B905). Special thanks to the study subjects and referring physicians for their participation in this study.
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Li, Xp., Li, J., Yan, H. et al. Tolerability, pharmacokinetics and pharmacodynamics of CMAB001, an anti-CD11a antibody, in Chinese healthy volunteers and psoriatic patients. Acta Pharmacol Sin 33, 1085–1094 (2012). https://doi.org/10.1038/aps.2012.65
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DOI: https://doi.org/10.1038/aps.2012.65
