A Phase I, single and continuous administration study of Safety, tolerability and pharmacokinetics of neorudin, a noval recombinant anticoagulant protein, in healthy subjects

AIMS: The aims of the study were to evaluate the tolerability, safety and pharmacokinetics of single and continuous administration of recombinant neorudin (EPR-hirudin, EH) by intravenous injection in healthy subjects, and to provide a safe dosage range for phase II clinical research. METHODS: A single and continuous administration dose phase I clinical study was conducted. Forty-four subjects were received EH as single-dose of 0.2-2.0 mg/kg by intravenous bolus plus drip; Eighteen healthy subjects were randomly divided into 3 dose groups (0.15-0.45 mg/kg/h) with 6 cases in each group in the continuous administration trial. RESULTS: Single or continuous doses of neorudin were generally well tolerated in healthy adult subjects. There were no serious adverse events (SAEs), and all adverse events (AEs) were mild to moderate. No subjects withdrew from the trial due to adverse events. There were no clinically relevant changes in physical examination, clinical chemistry, urinalysis or vital signs. The incidence of adverse events was not significantly related to the dose and systemic exposure. After the single-dose and continuous administration, the serum EH concentration reached a peak at 0.083h，the exposure increased with the increase of the administered dose with the mean half-life (T1/2) ranging from 1.7 to 2.5h, the clearance (Cl) ranging from 123.9 to179.7 mL/h/kg, and the apparent volume of distribution (Vd) ranging from 402.7 to 615.2 mL/kg. CONCLUSIONS: The safety, tolerability and pharmacokinetics characteristics of EH can be used to guide rational drug dosing and choose therapeutic regimens in subsequent clinical studies.