Safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers: a randomized, placebo-controlled, double-blind study

Abstract

The thrombopoietin mimetic peptide for injection is a second-generation thrombopoietin receptor agonist (TPO-RA) used in the treatment of patients with immune thrombocytopenia. The aim of the present study was to assess the safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers. A randomized, placebo-controlled, double-blind, dose-escalation study was conducted in healthy Chinese subjects aged 18–50 years. Thirty subjects received single subcutaneous injection of 0.3 μg/kg, 1.0 μg/kg, 2.0 μg/kg thrombopoietin mimetic peptide or placebo. Thrombopoietin mimetic peptide was safe and well tolerated at doses of 0.3–2.0 μg/kg. There was no significant change in mean platelet count (PLT) from baseline at the 0.3 μg/kg or placebo groups. The mean PLT of subjects in the 1.0 μg/kg and 2.0 μg/kg groups peaked at day 12 (± 1), began to decline around day 17, and returned to the baseline level at day 28 (± 1). Platelet aggregation rates of the three dose groups showed no significant change before and after administration. Serum concentrations of thrombopoietin mimetic peptide in all subjects were below the quantization limit. This was the first study to demonstrate that subcutaneous injection of thrombopoietin mimetic peptide at doses of 0.3–2.0 μg/kg was safe and well tolerated in Chinese healthy subjects. As a second-generation TPO-RA, thrombopoietin mimetic peptide is effective at improving PLT after single subcutaneous injection at dose of ≥1 μg/kg.

P lain l anguage s ummary

What is the context?

● Immune thrombocytopenia (ITP) is a rare, serious autoimmune disorder characterized by low platelet count (PLT) without an alternate cause. The treatment goal of ITP is to increase the platelet count to a safe level that can stop active bleeding and reduce the risks of future bleeding.

● Thrombopoietin receptor agonists (TPO-RAs, e.g. eltrombopag, avatrombopag, hetrombopag, and romiplostim) have shown high response rates in stimulating platelet production and reducing the risk of bleeding. TPO-RAs provide ITP patients with well-tolerated, long-term treatment choices.

What is new?

● The thrombopoietin mimetic peptide for injection is a new TPO-RAs developed by Shandong Quangang Pharmaceutical Co., Ltd. (China).

● This study showed that thrombopoietin mimetic peptide is effective at improving PLT after a single subcutaneous injection.

● The thrombopoietin mimetic peptide is safe and well-tolerated in Chinese healthy subjects.

What is the impact?

● This study provides evidence for the further development potential of the thrombopoietin mimetic peptide.

Keywords:

• China
• Pharmacodynamics
• pharmacokinetics
• thrombopoietin mimetic peptide for injection

Acknowledgements

We thank the United-Power Pharma Tech Co., Ltd (Beijing, China) for performing the concentration assays. We also thank the Department of Biostatistics, Peking University First Hospital for performing the statistical analysis.

Disclosure statement

Lei Song and Wen-ming Zhao are employees of Shandong Quangang Pharmaceutical Co., Ltd. which sponsored the clinical trial. The other authors have no conflicts of interest to declare.

Author’s contributions

Lei Song, Wen-ming Zhao, Xia Zhao and Yi-min Cui designed the study. Xiao-yan Sheng, Zhi-yan Liu, Jing zhao, Xia Zhao and Yi-min Cui conducted the clinical trial. Xiao-yan Sheng, Zhi-yan Liu and Jing zhao analyzed the results and drafted the manuscript. Lei Song, Wen-ming Zhao, Xia Zhao and Yi-min Cui participated in the interpretation of results and revised the manuscript. All authors read and approved the final manuscript.

Additional information

Funding

Funding This study was sponsored by Shandong Quangang Pharmaceutical Co., Ltd. (Jinan, China). The study was funded by the Key Research and Development Plan of Shandong Province of China (Major scientific and technological innovation projects) (2019JZZY021018).