Pharmacodynamic Equivalence of Ovine Enoxaparin to Porcine Enoxaparin (Lovenox®) in Healthy Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Indonesia University
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Maximum activity (Amax)
Study Overview
Brief Summary
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.
Detailed 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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy volunteers of both sexes aged 18 - 45 years with BMI 18 - 25 kg/m2 inclusive.
- •Have no clinically significant abnormalities based on medical history, clinical laboratory tests, vital sign measurements, 12-lead ECG results, and physical examination findings.
- •Willing to participate in the study by signing the informed consent.
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
- •Pregnancy or lactation
- •taking hormonal contraception (oral or injection)
Arms & Interventions
TR treatment sequence
Period 1-Test Treatment: Ovine enoxaparin sodium 60 mg SC injection, manufactured by Metiska Farma. Period 2-Reference Treatment: Porcine enoxaparin sodium 60 mg SC injection (Lovenox), manufactured by Sanofi, France.
Intervention: Ovine Enoxaparin (Drug)
TR treatment sequence
Period 1-Test Treatment: Ovine enoxaparin sodium 60 mg SC injection, manufactured by Metiska Farma. Period 2-Reference Treatment: Porcine enoxaparin sodium 60 mg SC injection (Lovenox), manufactured by Sanofi, France.
Intervention: Enoxaparin Prefilled Syringe [Lovenox] (Drug)
RT treatment sequence
Period 2-Reference Treatment: Porcine enoxaparin sodium 60 mg SC injection (Lovenox), manufactured by Sanofi, France. Period 1-Test Treatment: Ovine enoxaparin sodium 60 mg SC injection, manufactured by Metiska Farma.
Intervention: Ovine Enoxaparin (Drug)
RT treatment sequence
Period 2-Reference Treatment: Porcine enoxaparin sodium 60 mg SC injection (Lovenox), manufactured by Sanofi, France. Period 1-Test Treatment: Ovine enoxaparin sodium 60 mg SC injection, manufactured by Metiska Farma.
Intervention: Enoxaparin Prefilled Syringe [Lovenox] (Drug)
Outcomes
Primary Outcomes
Maximum activity (Amax)
Time Frame: Day -1 (periode 1 and 2), before dosing (pre-dose), and between 1 and 24 hours after dosing on day 1 (period 1 and 2)
Amax will be measured for anti-FXa activity, anti-FIIa activity and TFPI levels
Area under the effect curve (AUEC0-t)
Time Frame: Day -1 (periode 1 and 2), before dosing (pre-dose), and between 1 and 24 hours after dosing on day 1 (period 1 and 2)
The AUEC will be measured from time 0 to the last measured activity (AUEC0-t) of anti-FXa activity, anti-FIIa activity, and TFPI levels
Secondary Outcomes
- Adverse events(From informed consent signature until the study end)
Investigators
Prof. Arini Setiawati, PhD
Prof, PhD
Indonesia University