Safety, tolerability, pharmacodynamics, and pharmacokinetics of CJC-1134-PC in healthy Chinese subjects and type-2 diabetic subjects

ABSTRACT

Background

Glucagon-like peptide-1 (GLP-1) mimetics are widely used for treating type 2 diabetes (T2D) with pleiotropic effects on heart and kidneys. The safety/tolerability and pharmacokinetics/pharmacodynamics ((PK/PD) of CJC-1134-PC (a long-acting GLP-1) were investigated in Chinese.

Method

Two randomized, double-blind, placebo-controlled phase I studies were conducted. Study A: 30 healthy subjects received (subcutaneously injected) a single dose (2 mg) or titrate doses (2 + 3 and 2 + 3 + 4 mg at weekly intervals) of CJC-1134-PC. Study B: 49 T2D subjects received 10 weekly doses (1, 2, 3, and 4 mg).

Result

CJC-1134-PC was well tolerated with gastrointestinal (GI) side effects. Higher doses increased the adverse events risk. CJC-1134-PC was steadily absorbed, with maximum plasma concentrations(C_max) occurring at 36–72 h and 48 h after administration in healthy and T2D subjects, respectively. The steady-state exposures in T2D subjects increased more than the dose-proportionality(1–3 mg). The mean t_1/2 ranged from 111.6 to 127.6 h. After four- five weeks of targeting doses, steady state was reached in T2D subjects with apparent accumulation effect. At week 11 for T2D subjects, HbA1c mean baseline change was significantly different than that of the placebo, and the fasting plasma glucose (FPG) was not significantly altered.

Conclusion

The safety and PK/PD profiles of weekly CJC-1134-PC doses support Phase II studies with guidance on optimal-dose selection. Clinical trial registration: ChiCTR-IPC-15007190

KEYWORDS:

• Glucagon-like peptide-1 mimetic
• CJC-1134-PC
• safety
• pharmacodynamics
• pharmacokinetics

Acknowledgments

We would like to thank all the subjects in these trials. This study was sponsored by Hebei Changshan Biochemical Pharmaceutical Co., Ltd. This work was also financially supported by the capital construction funds within the provincial budget in 2020 (innovation capacity construction, project: 2020C038-1).

Author Contributions

Conceptualization, Zhiwen Yao and Yanhua Ding; methodology, Yanhua Ding, Qiang Xie, Xiping Liu; validation, Yanhua Ding, formal analysis, Hong Zhang, Cuiyun Li; investigation, Xiaoxue Zhu, Cuiyun Li, Min Wu, Lizhi Yang; resources, Zhiwen Yao; writing—original draft preparation, Cuiyun Li; writing—review and editing, Zhiwen Yao and Yanghua Ding; supervision, Yanghua Ding. All authors have read and agreed to the published version of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose