Pharmacodynamics Study of Enoxalow Compared to Clexane in Healthy Subjects After Intravenous Administration

NCT ID: NCT01692171

Last Updated: 2022-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2013-10-31

Brief Summary

The hypothesis of this trial is that the test drug (Enoxalow® - T) pharmacodynamics parameters are similar to the comparator drug (Clexane® - C) in healthy subjects following administration of single intravenous dose. The objective of this randomized, crossover, clinical trial is to evaluate the pharmacodynamic profile of the test drug Enoxalow® - T produced by Blau Farmacêutica, compared to the comparator drug Clexane®, produced by Sanofi-Aventis, by determining pharmacodynamic activities (including anti FXa and anti-FIIa), as surrogate markers for their circulating concentrations of the drug.

Detailed Description

In addition other pharmacodynamic tests such as Tissue Factor Pathway Inhibitor (TFPI) activity, as well as the ratio of anti-FXa and anti-FIIa activity will be compared as secundary obectives.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Teste

Enoxalow (Heparin, Low-Molecular-Weight) - Blau Farmacêutica S/A.

Group Type: EXPERIMENTAL

Heparin, Low-Molecular-Weight

Intervention Type: DRUG

single intravenous administration of 3mg/Kg of the test drug and the comparator drug, according to randomization, in a crossover design, each administration separated by 6 days of washout.

Comparador

Clexane (Heparin, Low-Molecular-Weight)- Sanofi-Aventis

Group Type: ACTIVE_COMPARATOR

Heparin, Low-Molecular-Weight

Intervention Type: DRUG

single intravenous administration of 3mg/Kg of the test drug and the comparator drug, according to randomization, in a crossover design, each administration separated by 6 days of washout.

Interventions

Heparin, Low-Molecular-Weight

single intravenous administration of 3mg/Kg of the test drug and the comparator drug, according to randomization, in a crossover design, each administration separated by 6 days of washout.

Intervention Type: DRUG

Other Intervention Names

Clexane; Enoxalow

Eligibility Criteria

Inclusion Criteria

• Agree to all the purposes of the study by signing and dating the Informed Consent;
• Male, aged between 18 and 55 years, clinically healthy;
• BMI between 18.5 and 30;

Exclusion Criteria

• Participation in clinical trials in the 12 months preceding the trial;
• Presence of pulmonary, cardiovascular, neurological, endocrine, gastrointestinal, genitourinary or other systems diseases;
• Acute disease in the period of 07 days before the beginning of the practical phase (administration of the drug) of the study;
• Chronic administration of medications for hypertension, diabetes or any other disease that requires continuous use of any drug;
• Hemoglobin <13 g/dL;
• Continuous use of oral anticoagulants, platelet inhibitors or anti-inflammatory drugs;
• Use of medications that interact with enoxaparin;
• History of gastrointestinal bleeding, deep vein thrombosis or pulmonary embolism that may interfere with the clinical outcome of the study;
• History of coagulopathy and bleeding diathesis;
• Presence of changes in physical examination suggestive of coagulation disorders (bruising, petechiae, or bruising);
• Body weight < 45 kg or > 100 kg;
• Absolute platelet count below 100 x 109 / L;
• History of chronic bleeding;
• History of acute haemorrhage in the past 30 days;
• History of sensitivity to mammalian-derived biological products, albumin or any component of the formulation;
• History of allergy or Steven Johnson disease;
• Current or previous history (under 12 months) use of illicit drugs and tobacco;
• History of alcohol abuse, current or previous (within 12 months);
• At the discretion of the Principal Investigator of the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Blau Farmaceutica S.A.

INDUSTRY

Sponsor Role: collaborator

Azidus Brasil

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Márcia Guidone, manager

Role: STUDY_DIRECTOR

Blau Farmaceutica S.A.

Locations

LAL Clinica

Valinhos, São Paulo, Brazil

Countries

Brazil

References

Bara L, Billaud E, Gramond G, Kher A, Samama M. Comparative pharmacokinetics of a low molecular weight heparin (PK 10 169) and unfractionated heparin after intravenous and subcutaneous administration. Thromb Res. 1985 Sep 1;39(5):631-6. doi: 10.1016/0049-3848(85)90244-0. No abstract available.

Reference Type: BACKGROUND

PMID: 4082105 (View on PubMed)

Bruno R, Baille P, Retout S, Vivier N, Veyrat-Follet C, Sanderink GJ, Becker R, Antman EM. Population pharmacokinetics and pharmacodynamics of enoxaparin in unstable angina and non-ST-segment elevation myocardial infarction. Br J Clin Pharmacol. 2003 Oct;56(4):407-14. doi: 10.1046/j.1365-2125.2003.01904.x.

Reference Type: BACKGROUND

PMID: 12968985 (View on PubMed)

EMA 2009. European Medicines Agency.Guideline on non-clinical and clinical development of similar biological medical products containing low-molecular-weightheparins:EMEA/CHMP/BMWP/118264/2007.

Reference Type: BACKGROUND

FDA 2011. Food and Drug Administration. Draft Guidance on Enoxaparin Sodium.

Reference Type: BACKGROUND

Gerotziafas GT, Petropoulou AD, Verdy E, Samama MM, Elalamy I. Effect of the anti-factor Xa and anti-factor IIa activities of low-molecular-weight heparins upon the phases of thrombin generation. J Thromb Haemost. 2007 May;5(5):955-62. doi: 10.1111/j.1538-7836.2007.02477.x.

Reference Type: BACKGROUND

PMID: 17461929 (View on PubMed)

Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Raschke R, Granger C, Ohman EM, Dalen JE. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest. 2001 Jan;119(1 Suppl):64S-94S. doi: 10.1378/chest.119.1_suppl.64s. No abstract available.

Reference Type: BACKGROUND

PMID: 11157643 (View on PubMed)

Kuczka K, Harder S, Picard-Willems B, Warnke A, Donath F, Bianchini P, Parma B, Blume H. Biomarkers and coagulation tests for assessing the biosimilarity of a generic low-molecular-weight heparin: results of a study in healthy subjects with enoxaparin. J Clin Pharmacol. 2008 Oct;48(10):1189-96. doi: 10.1177/0091270008322911. Epub 2008 Aug 20.

Reference Type: BACKGROUND

PMID: 18716314 (View on PubMed)

Mousa SA, Bozarth J, Barrett JS. Pharmacodynamic properties of the low molecular weight heparin, tinzaparin: effect of molecular weight distribution on plasma tissue factor pathway inhibitor in healthy human subjects. J Clin Pharmacol. 2003 Jul;43(7):727-34.

Reference Type: BACKGROUND

PMID: 12856386 (View on PubMed)

Wannmacher L. Heparinas de baixo peso molecular: evidências que fundamentam indicações. Uso Racional de Medicamentos: Temas Selecionados 2007:4:1-6.

Reference Type: BACKGROUND

Other Identifiers

Versão 01 datada de 20.06.2012

Identifier Type: OTHER

Identifier Source: secondary_id

ENOBLA0612IV-I

Identifier Type: -

Identifier Source: org_study_id