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