Enoxaparin Clinical Trial
Official title:
Pharmacodynamic Equivalence of Ovine Enoxaparin to Porcine Enoxaparin (Lovenox®) in Healthy Volunteers
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.
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
1. On day-1 of period 1, subjects will be given in fasting condition, a single s.c.
injection of the test or the reference drug.
2. Blood samples to assess PD parameters will be collected in both study periods at the
following time points: pre-dose, and 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, 20,
and 24 hours after dosing on Day-1 (16 sampling points).
3. Nine (9) mL of blood will be drawn from vena cubiti with a needle of 19 to 21 gauge with
a maximum of 1 minute pressure with tourniquet, the first 3 mL of blood will be
collected in an empty tube (to be thrown away), the second 3 mL of blood will be
collected in a blood collection tube containing citrate, theophylline, adenosine, and
dipyridamole (CTAD tube) for anti-FXa and anti-FIIa, and the third 3 mL of blood will be
collected in a citrate tube for TFPI. In case of failure in blood drawing, the
phlebotomist should change the site of blood drawing and change the needle used.
4. Subjects will return to the clinic after a wash-out period of at least 7 days, and on
day-1 of period 2, they will be crossed over to receive a single s.c. dose of the
alternate drug.
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).
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
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