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This study is designed as a randomized, open-label, 2-way cross-over, single dose study with at least 7 days wash-out period. The objective of this study is to demonstrate the pharmacodynamic / pharmacokinetic equivalence of ovine enoxaparin to the reference product, the originator porcine enoxaparin, Lovenox® from Sanofi, and to assess its safety and tolerability in healthy volunteers.
Full description
Low molecular-weight heparins (LMWHs) are derived from unfractionated heparin (UFH) by chemical or enzymatic depolymerization. Enoxaparin is one of the most widely used LMWHs and is obtained by alkaline depolymerization of heparin benzyl ester derived from porcine intestinal mucosa. In contrast to UFH, enoxaparin has higher and more consistent bioavailability after s.c. administration compared with UFH and has longer plasma half-life.
Because of difficulties in chemical detection of LMWH, conventional pharmacokinetic studies cannot be performed. LMWH absorption and elimination are studied using pharmacodynamic surrogate markers, i.e. anti-FXa activity. Measurement of this pharmacodynamic activities is used to compare the biosimilar/ generic products to the reference LMWH.
This study is designed as a randomized, open-label, 2-way cross-over, single dose study with at least 7 days wash-out period. The objective of this study is to demonstrate the pharmacodynamic / pharmacokinetic equivalence of ovine enoxaparin to the reference product, the originator porcine enoxaparin, Lovenox® from Sanofi, and to assess its safety and tolerability in healthy volunteers.
The test drug is ovine enoxaparin sodium 60 mg (0.6 mL taken from 1.0 mL vial containing 100 mg = 10,000 IU anti-FXa), from Metiska Farma. Meanwhile, the reference drug is enoxaparin sodium 60 mg (Lovenox® 0.6 mL prefilled syringe containing 60 mg = 6,000 IU anti-FXa) from Sanofi, France. The drugs are not similar in appearance: ovine enoxaparin is supplied in vials, whereas Lovenox® is supplied as pre-filled syringes, both are given as s.c. injection. An unblinded pharmacist will prepare the study drug, and an unblinded medical doctor will inject the study drug.
Study procedures
Anti-FXa activity will be determined by a chromogenic method using a commercial kit (STA-Liquid anti-FXa, Diagnostica Stago S.A.S, France) within 4 hours after sample collection at room temperature. Meanwhile, anti-FIIa activity will be measured by a chromogenic method using a commercial kit (Biophen anti-FIIa, STA Compact Max, France) within 4 hours after sample collection at room temperature, and TFPI levels will be measured using a commercial ELISA kit (Abcam PLC, Cambridge, UK).
Enrollment
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Inclusion criteria
Exclusion criteria
Female < 45 kg or male < 57 kg
Calculated (Cockroft & Gault formula) ClCr < 80 mL/min
History of or positive test result for alcohol abuse or drug addiction.
History of relevant drug and/or food allergies.
Any prescription drug (especially antiplatelet or anticoagulant drug) or OTC medication including herbal, supplement, etc. that could affect coagulation within 2 weeks before study dosing.
Administration of any investigational drug within 60 days before study drug dosing.
Taking anti TB rifampicin within 60 days before study drug dosing.
A positive test for HIV (1 or 2) Ab, HBsAg, or HepC Ab.
A positive fecal occult blood at screening.
History and/or current conditions of bleeding tendency.
History of thrombocytopenia, including heparin-induced (by anamnesis).
Known history of hypersensitivity to drugs with a chemical structure similar to enoxaparin sodium (eg. UFH, LMWH) or to pork or lamb products.
Females: - during menstruation period
Primary purpose
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20 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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