Pharmacokinetics and pharmacodynamics of a polyethylene glycol (PEG)-conjugated GLP-receptor agonist once weekly in Chinese patients with type 2 diabetes

The Journal of Clinical PharmacologyVolume 55, Issue 2 p. 152-158 Therapeutics Pharmacokinetics and pharmacodynamics of a polyethylene glycol (PEG)-conjugated GLP-receptor agonist once weekly in Chinese patients with type 2 diabetes Guang-Ran Yang MD, PhD, Guang-Ran Yang MD, PhD Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaSearch for more papers by this authorXiu-Li Zhao MD, PhD, Corresponding Author Xiu-Li Zhao MD, PhD Department of Cardiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China Corresponding Author: Professor Jin-Kui Yang, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China Email: [email protected] **Corresponding Author: Professor Xiu-Li Zhao, Department of Cardiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730 Email: [email protected]Search for more papers by this authorFan Jin PhD, Fan Jin PhD Analytic laboratory of COVANCE, ChinaSearch for more papers by this authorLi-Hong Shi PhD, Li-Hong Shi PhD Analytic laboratory of COVANCE, ChinaSearch for more papers by this authorJin-Kui Yang MD, PhD, Corresponding Author Jin-Kui Yang MD, PhD Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China Corresponding Author: Professor Jin-Kui Yang, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China Email: [email protected] **Corresponding Author: Professor Xiu-Li Zhao, Department of Cardiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730 Email: [email protected]Search for more papers by this author Guang-Ran Yang MD, PhD, Guang-Ran Yang MD, PhD Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaSearch for more papers by this authorXiu-Li Zhao MD, PhD, Corresponding Author Xiu-Li Zhao MD, PhD Department of Cardiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China Corresponding Author: Professor Jin-Kui Yang, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China Email: [email protected] **Corresponding Author: Professor Xiu-Li Zhao, Department of Cardiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730 Email: [email protected]Search for more papers by this authorFan Jin PhD, Fan Jin PhD Analytic laboratory of COVANCE, ChinaSearch for more papers by this authorLi-Hong Shi PhD, Li-Hong Shi PhD Analytic laboratory of COVANCE, ChinaSearch for more papers by this authorJin-Kui Yang MD, PhD, Corresponding Author Jin-Kui Yang MD, PhD Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China Corresponding Author: Professor Jin-Kui Yang, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China Email: [email protected] **Corresponding Author: Professor Xiu-Li Zhao, Department of Cardiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730 Email: [email protected]Search for more papers by this author First published: 28 August 2014 https://doi.org/10.1002/jcph.386Citations: 11 Guang-Ran Yang and Xiu-Li Zhao contributed equally to this paper. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract This multi-center, randomized, double-blind, multiple dose-escalation study was conducted to assess the pharmacokinetics and pharmacodynamics of a newly developed polyethylene glycol (PEG)-conjugated glucagon-like peptide-1 (GLP-1) receptor agonist, PEX168 once weekly in Chinese patients with type 2 diabetes (T2DM). Fifty patients aged 20–65 years, either treatment-naive or having been treated with single oral antidiabetic agents were eligible. Antidiabetic agents were stopped for 14 days before the study was initiated. Patients were allocated randomly into groups with subcutaneous PEX168 or placebo once-weekly for 8 weeks followed by 6 weeks observation. From baseline to 8 weeks, HbA1c were decreased by up to 0.0, 0.2, 0.6, 0.9, and −0.4% in the 50, 100, 200, 300 μg PEX168 groups, and placebo group respectively. The mean elimination half-life of PEX168 was 131.8–139.8 hours. The mean tmax was 67.3 hours. Steady-state plasma PEX168 concentrations were attained after 4 weeks. PEX168 once-weekly were tolerable by the patients: adverse effects reported ranged from ‘mild' to ‘moderate'. The most frequent drug-related adverse effects were nausea, vomiting, and diarrhea of mild to moderate severity. Administration of the PEG-conjugated GLP-1 receptor agonist PEX168 resulted in dose-proportional pharmacokinetic and antidiabetic pharmacodynamic activity. Citing Literature Supporting Information Additional supporting information may be found in the online version of this article at the publisher's web-site. Filename Description jcph386-sm-0001-SuppTab_S1.doc48 KB Table: Overview of adverse Events-- PEX168 Phase I Study Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume55, Issue2February 2015Pages 152-158 RelatedInformation