Bioequivalence and safety evaluation of domestic dalteparin sodium injection in healthy volunteers

HU Ting-ting; WANG Lan-tian; ZHAO Xian-mei; KANG Hui; YONG Xiao-lan

Abstract：Objective:To evaluate the pharmacokinetic behaviors and bioequivalence of two kinds of dalteparin sodium injections after subcutaneous injection in healthy Chinese volunteers.Methods:A single-dose,randomized,open label,two way crossover study was designed to evaluate the bioequivalence and safety of domestic dalteparin sodium injection in healthy Chinese male volunteers under fasting condition.Twenty-six volunteers were recruited,including 2 for pilot trial,and 24 for formal trial.The subjects were divided into two groups randomly and subcutaneously administered respectively with single dose of test or reference preparation of dalteparin sodium injection (0.2 mL∶ 5 000 IU).Blood samples were collected at preset time.The wash-out period was one week.Emax,AUEC0～t and AUEC0～∞ were calculated by non-compartmental analysis,and the 90％ confidence intervals (CIs) of the ratios between the test and reference preparations were assessed.The safety profile was evaluated by adverse events (AEs) record,and assessed by physical examination,vital signs and clinical laboratory results.All the 26 subjects were included in the safety set (SS) and the 24 subjects in the formal trial were brought into per-protocol set (PPS).Results:All of the 26 subjects completed this trial.The 90％ CIs for the ratios of Emax and AUEC0～tof ATⅡ a were 95.36％～ 111.77％,83.80％～ 110.15％ and those of ATXa were 101.50％～114.30％,103.57％～116.46％,respectively.The above-mentioned values met the predetermined criteria for assuming bioequivalence.Eight subjects reported a total of 10 mild AEs (3 reported by 3 subjects who received the test preparation,and 7 reported by 6 subjects who received the reference preparation).No serious adverse events (SAEs) were observed.Conclusion:In this single-dose study,the test and reference preparations of dalteparin sodium injection met the regulatory definition for assuming bioequivalence in Chinese healthy male volunteers.The domestic preparation is generally well tolerated in the test population.