A Randomised, Multicenter, Open-Label, Parallel Group Study to Assess the Safety of PEG-Hirudin (SPP200) Compared to Unfractionated Heparin as Anticoagulant Treatment in Patients Undergoing Haemodialysis Via an Arteriovenous Graft

The study will look at the safety profile (unwanted effects) of the long-lasting anticoagulant PEG-hirudin (SPP200) and compare these unwanted effects to those of unfractionated heparin, commonly used in haemodialysis to avoid clotting of the graft and of the haemodialysis machine.

开始日期2003-11-01

申办/合作机构

Speedel Pharma AG

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100 项与 Pegmusirudin 相关的临床结果

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100 项与 Pegmusirudin 相关的转化医学

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项与 Pegmusirudin 相关的文献（医药）

2023-01-01·The Journal of toxicological sciences

The toxicity assessment of neorudin in cynomolgus monkeys.

Article

作者: Zhang, Lin ; Zhou, Xing-chen ; Wu, Chu-tse ; Jin, Ji-de ; Zheng, Can ; Liu, Yu-bin ; Ren, Bo-yuan ; Liu, Yun ; Wei, Jin-feng

In this study, the toxicity effects on circulatory system and respiratory system, and the acute toxicity test of recombinant neorudin (EPR-hirudin, EH) in cynomolgus monkeys were evaluated to provide reference information for clinical studies. Eighteen cynomolgus monkeys were randomly divided into three groups for single intravenous administration of 3, 30 mg/kg EH and normal saline, respectively. The changes of respiratory frequency, respiratory intensity, blood pressure and electrocardiogram before and after administration were recorded. In acute toxicity test, six cynomolgus monkeys were intravenously received EH at a single dose of 171, 257, 385, 578, 867 and 1300 mg/kg respectively. The vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of the animals were determined before administration and on the 7th and 14th day after administration. As the results showed that there were no significant abnormal changes in respiratory frequency, respiratory intensity, blood pressure or electrocardiogram in cynomolgus monkeys after receiving EH at 3 mg/kg and 30 mg/kg, and there was no statistical difference between the treated groups and normal saline group. In the acute toxicity test, no significant abnormalities were observed in vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of six cynomolgus monkeys at day 7 and 14 after EH administration. Furthermore, autopsies of all cynomolgus monkeys showed no abnormalities. The results of toxicokinetics showed that AUClast of the drug increased in proportion to the EH dose in the range of 171-578 mg/kg, and increased in over proportion to the EH dose in the range of 578-1300 mg/kg. The variation of Cmax was basically consistent with AUClast. In a sum, A single intravenous injection of 3 and 30 mg/kg of EH did not affect the circulatory system and respiratory system in cynomolgus monkeys and the maximum tolerated dose of EH in cynomolgus monkey is over 1300 mg/kg (equivalent to 619-1300 times of the proposed clinical equivalent dose).

2021-05-01·Pharmacology Research & Perspectives4区 · 医学

A phase I, single and continuous dose administration study on the safety, tolerability, and pharmacokinetics of neorudin, a novel recombinant anticoagulant protein, in healthy subjects

4区 · 医学

ArticleOA

作者: Dou, Guifang ; Wang, Meixia ; Zhou, Ying ; Liu, Yubin ; Wu, Chu‐tse ; He, Jia ; Jin, Jide ; Xia, Xia ; Dong, Xiaona ; Zhang, Lin

AbstractThe aim of this study was to evaluate the tolerability, safety, and pharmacokinetics of single and continuous dose administration of recombinant neorudin (EPR‐hirudin, EH) by intravenous administration in healthy subjects, and to provide a safe dosage range for phase II clinical research. Forty‐four subjects received EH as a single dose of between 0.2 and 2.0 mg/kg by intravenous bolus and drip infusion. In addition, 18 healthy subjects were randomly divided into three dose groups (0.15, 0.30, and 0.45 mg/kg/h) with 6 subjects in each group for the continuous administration trial. Single or continuous doses of neorudin were generally well tolerated by healthy adult subjects. There were no serious adverse events (SAEs), and all adverse events (AEs) were mild to moderate. Moreover, no subjects withdrew from the trial because of AEs. There were no clinically relevant changes in physical examination results, clinical chemistry, urinalysis, or vital signs. The incidence of adverse events was not significantly related to drug dose or systemic exposure. After single‐dose and continuous administration, the serum EH concentration reached its peak at 5 min, and the exposure increased with the increase in the administered dose. The mean half‐life (T1/2), clearance (Cl), and apparent volume of distribution (Vd) of EH ranged from 1.7 to 2.5 h, 123.9 to 179.7 ml/h/kg, and 402.7 to 615.2 ml/kg, respectively. The demonstrated safety, tolerability, and pharmacokinetic characteristics of EH can be used to guide rational drug dosing and choose therapeutic regimens in subsequent clinical studies.Clinical trial registration: Chinadrugtrials.org identifier: CTR20160444.

2020-10-01·Thrombosis Research3区 · 医学

Predicting the metabolic characteristics of neorudin, a novel anticoagulant fusion protein, in patients with deep vein thrombosis

3区 · 医学

Article

作者: Jin, Jide ; Dou, Guifang ; Meng, Zhiyun ; Liu, Jianglin ; Gan, Hui ; Dong, Xiaona ; Gu, Ruolan ; Zhu, Xiaoxia

INTRODUCTIONRecombinant neorudin (EPR-hirudin, EH) is an inactive prodrug that is converted to its active metabolite, hirudin variant 2-Lys47 (HV2), at the thrombus site. We aimed to investigate the mechanism underlying site-selective bioconversion of EH to HV2 at the thrombus target site and metabolic transformation of EH in patients with deep vein thrombosis (DVT).MATERIALS AND METHODSMetabolites in healthy volunteer plasma and urine after intravenous administration of EH were determined to elucidate how EH was metabolised after releasing HV2 at the target site in patients with DVT. After intravenous administration of EH in rats with venous thrombosis, the concentrations of EH in the blood and thrombus and the antithrombotic activity of EH were measured to predict whether EH could release HV2 at the thrombus site to exert anticoagulant effect in patients with DVT.RESULTSIn healthy volunteers, EH and HV2 were predominantly excreted in the urine. Nine EH metabolites and ten HV2 metabolites truncated at the C-terminal were identified as N-terminal fragments, and these had the same cleavage sites. In rats with venous thrombosis, the area under the curve ratio of HV2 between the thrombus and blood was 29.5. The weight of wet thrombus was decreased with the production of HV2 by the cleavage of EH. The prothrombin time (PT) and prothrombin time (TT) changed proportionally to the concentration of EH and HV2 in the blood.CONCLUSIONEH selectively accumulates and releases HV2 in the thrombus to exert antithrombotic effects, thus lowering the bleeding risk. Moreover, after conversion, EH may follow the same metabolic profile as that of HV2 in patients with DVT.

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适应症	最高研发状态	国家/地区	公司	日期
血管移植物阻塞	临床2期	美国	Speedel Pharma AG	2003-11-01
终末期肾脏病	临床2期	美国	Speedel Pharma AG	2003-11-01
不稳定型心绞痛	临床2期	-	Abbott Laboratories	-
不稳定型心绞痛	临床2期	-	Novartis Pharma AG	-
凝血障碍	临床2期	-	Abbott Laboratories	-
凝血障碍	临床2期	-	Novartis Pharma AG	-
冠心病	临床2期	-	Abbott Laboratories	-
冠心病	临床2期	-	Novartis Pharma AG	-