Generic and Branded Enoxaparin Bioequivalence: A Clinical and Experimental Study

The clinical studyThis single-dose, randomized-sequence, open-label study was conducted at the emergency department (ED) of Fattouma Bourguiba University Hospital, Tunisia.It was performed in accordance with the revised declaration of Helsinki for Biomedical Research involving human subjects and the Guidelines for Good Clinical Practice.The protocol was approved by the ethics committee of our institution.This trial was carried out between December 2012 and April 2013.Prior to undergoing any screening procedures, all included patients provided written informed consent.Patients were included if they were older than 18 years and fulfilled the criteria of ACS within 48H of chest pain onset: signs suggestive of ACS without ST-segment elevation myocardial infarction, and electrocardiographic changes AbstractOur aim is to compare a new generic version of enoxaparin (Enoxa ® ) with the parent brand (Lovenox ® ).We included patients with acute coronary syndrome (ACS) for the clinical study and healthy volunteers for the experimental study.ACS patients were randomly assigned to receive a bolus of Enoxa ® (n=86) or Lovenox ® (n=83) and serum anti-Xa activity was measured 4 hours thereafter.For experimental study, blood from healthy volunteers was used to compare the effect of both formulations on thrombin generation in citrated platelet-poor plasma (PPP).We measured the half maximal inhibitory concentration of the drug (IC50) that is required to decrease 50% in-vitro thrombin generation parameters the mean rate index (MRI) and the endogenous thrombin potential (ETP).Both IC50 MRI and IC50 ETP were calculated in PPP.In ACS patients, serum anti-Xa activity was found not different between Enoxa ® and Lovenox ® .Median anti Xa activity measured 4 hours after the initial bolus was 0.39 IU anti-Xa/ml [95 % CI 0.31-0.53]and 0.34 IU anti-Xa/ml [95% CI 0.27-0.53],for the Enoxa ® group and Lovenox ® group respectively.No difference in major cardiovascular events was observed during hospital stay.In healthy volunteers, IC50 MRI and IC50 ETP were similar between Lovenox ® and Enoxa ® [(2.5 µg/ml ± 0.2 µg/ml) versus (2.3 µg/ml ± 0.1µg/ml)] and [(4.8 µg/ml ± 0.8 µg/ml) versus (4.1 µg/ml ± 0.1 µg/ml) respectively for IC50 MRI and IC50 ETP; (p=0.2)].With both formulations, anti-Xa activity and anti-Xa/anti-IIa ratio were similar.The generic enoxaparin Enoxa ® met the main regulatory criteria of bioequivalence with the branded product.