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Polyethylene glycol loxenatide (PEX168) in subjects with renal impairment: A pharmacokinetic study
Author(s) -
Wang Jianwen,
Huang Jie,
Li Wei,
Tang Shiqi,
Sun Jian,
Zhang Xianming,
Liu Jun,
Yi Bin,
Liu Jishi,
Zhang Xingfei,
Yang Qian,
Yang Xiaoyan,
Yang Shuang,
Yang Guoping,
Zhang Hao
Publication year - 2019
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14091
Subject(s) - medicine , pharmacokinetics , renal function , adverse effect , gastroenterology , urology
Aims Type 2 diabetes mellitus (T2DM) is commonly complicated by renal impairment. Polyethylene glycol loxenatide (PEX168) is a novel long‐acting glucagon‐like peptide‐1 receptor agonist for T2DM. PEX168 pharmacokinetics was studied to identify requirements for dose‐modification in T2DM complicated by renal impairment. Methods This was a single‐centre, open‐labelled, parallel‐group, single‐dose, phase I clinical trial of patients with mild and moderate renal impairment, and with or without T2DM. Age‐, sex‐ and body mass index‐matched subjects with normal renal function, and with or without T2DM were recruited as controls. Subjects received a single abdominal subcutaneous injection of PEX168 200 μg. Pharmacokinetic samples were taken at 0, 24, 48, 72, 96, 120, 144, 216, 312, 480, 648 and 720 hours. Results Twenty‐three patients were included in the pharmacokinetics analysis. Vz/F and CL/F were lower in the moderate impairment group than in the other groups. The mean t 1/2 (163 hours) in the moderate impairment group was prolonged compared to the mild impairment (117 hours) and normal (121 hours) groups. AUC 0–inf increased by 13 and 100.7% in patients with mild and moderate renal impairment, respectively. Most adverse events were mild gastrointestinal disorders, with only 1 serious adverse event observed. Conclusion A single dose of 200 μg of PEX168 was in general well tolerated in patients with renal impairment. The in vivo clearance rate of PEX168 in patients with moderate renal impairment is slower than in patients with mild renal impairment and normal renal function and dose adjustment might be required ( ClinicalTrials.org #NCT02467790).