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

Healthy Clinical Trial

Official title:

Pharmacodynamics Study of Enoxalow, Produced by Blau Farmacêutica S/A, Compared to Clexane, Produced by Sanofi-Aventis Farmacêutica Ltda, in Healthy Subjects After Intravenous Administration.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01692171
• Other study ID #: ENOBLA0612IV-I
• Secondary ID: Versão 01 datada
• Status: Completed
• Phase: Phase 1
• Start date: February 28, 2013
• Est. completion date: October 31, 2013

Study information

• Verified date: October 2022
• Source: Azidus Brasil
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 31, 2013
• Est. primary completion date: October 31, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Brazil	LAL Clinica	Valinhos	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Azidus Brasil	Blau Farmaceutica S.A.

Country where clinical trial is conducted

Brazil, 

References & Publications (9)

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. — View Citation

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. — View Citation

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.

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 Draft Guidance on Enoxaparin Sodium.

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. Erratum in: J Thromb Haemost. 2007 Jun;5(6):1343. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the pharmacodynamic profile of the drug test in comparison to the comparator through the measurement of the activity of the Anti-FXa and anti-FIIa markers	Post drug administration blood samples were collected at following times - 0; 0:10; 0:20; 0:30; 00:40 12:50; 1; 1:30; two; 2:30; 3; 3:30; 4; 5; 6; 8; 10; 12; 16:24 (± 30) hours after.	The day after admission
Secondary	Assess the pharmacodynamic profile of the drug test in comparison to the comparator through the measurement of the activity of the TFPI marker and ratio of Anti-FXa and anti-FIIa.	Post drug administration blood samples were collected at following times - 0; 0:10; 0:20; 0:30; 00:40 12:50; 1; 1:30; two; 2:30; 3; 3:30; 4; 5; 6; 8; 10; 12; 16:24 (± 30) hours after.	The day after admission