Pharmacodynamic Equivalence of Ovine Enoxaparin to Lovenox®

NCT04402762 | Completed Phase 1 DMC

• 1 other identifier: CRSU.P.Enox/06.01/11/19
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Enoxaparin

Keywords

pharmacodynamic equivalence; anticoagulant; antithrombotic

Outcome Measures

Primary Outcomes (2)

• Maximum activity (Amax)

  Amax will be measured for anti-FXa activity, anti-FIIa activity and TFPI levels

  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)

• Area under the effect curve (AUEC0-t)

  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

  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)

Secondary Outcomes (1)

• Adverse events

  From informed consent signature until the study end

Study Arms (2)

TR treatment sequence

EXPERIMENTAL

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.

Drug: Ovine Enoxaparin; Drug: Enoxaparin Prefilled Syringe [Lovenox]

RT treatment sequence

ACTIVE COMPARATOR

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.

Drug: Ovine Enoxaparin; Drug: Enoxaparin Prefilled Syringe [Lovenox]

Interventions

Ovine Enoxaparin DRUG

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.

Also known as: Ovine Enoxaparin Sodium, Ovine Enoxaparin (Metiska Farma)

RT treatment sequence; TR treatment sequence

Enoxaparin Prefilled Syringe [Lovenox] DRUG

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.

Also known as: Active comparator

RT treatment sequence; TR treatment sequence

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Indonesia University: lead
• PT Metiska Farma: collaborator

Study Sites (1)

Pharma Metric Labs

Jakarta Pusat, Jakarta Special Capital Region, 10520, Indonesia

Location

Related Publications (2)

• Lee S, Raw A, Yu L, Lionberger R, Ya N, Verthelyi D, Rosenberg A, Kozlowski S, Webber K, Woodcock J. Scientific considerations in the review and approval of generic enoxaparin in the United States. Nat Biotechnol. 2013 Mar;31(3):220-6. doi: 10.1038/nbt.2528.

  PMID: 23471071 RESULT

• Martinez Gonzalez J, Monreal M, Ayani Almagia I, Llaudo Garin J, Ochoa Diaz de Monasterioguren L, Gutierro Aduriz I. Bioequivalence of a biosimilar enoxaparin sodium to Clexane(R) after single 100 mg subcutaneous dose: results of a randomized, double-blind, crossover study in healthy volunteers. Drug Des Devel Ther. 2018 Mar 19;12:575-582. doi: 10.2147/DDDT.S162817. eCollection 2018.

  PMID: 29593380 RESULT

Related Links

• EMA Assessment report for Inhixa (enoxaparin sodium), 2016

MeSH Terms

Interventions

Enoxaparin

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Arini Setiawati, Prof, PhD

  Clinical Research Supporting Unit, Faculty of Medicine, University of Indonesia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof, PhD

Model Details: Randomized, open-label, 2-way cross-over, single-dose study with at least 7 days wash-out period.

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: May 27, 2020
• Study Start: December 20, 2019
• Primary Completion: April 17, 2020
• Study Completion: May 3, 2020
• Last Updated: May 27, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)