<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01692171</url>
  </required_header>
  <id_info>
    <org_study_id>ENOBLA0612IV-I</org_study_id>
    <secondary_id>Versão 01 datada de 20.06.2012</secondary_id>
    <nct_id>NCT01692171</nct_id>
  </id_info>
  <brief_title>Pharmacodynamics Study of Enoxalow Compared to Clexane in Healthy Subjects After Intravenous Administration</brief_title>
  <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.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azidus Brasil</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Blau Farmaceutica S.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Azidus Brasil</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The hypothesis of this trial is that the test drug (Enoxalow® - T) pharmacodynamics&#xD;
      parameters are similar to the comparator drug (Clexane® - C) in healthy subjects following&#xD;
      administration of single intravenous dose. The objective of this randomized, crossover,&#xD;
      clinical trial is to evaluate the pharmacodynamic profile of the test drug Enoxalow® - T&#xD;
      produced by Blau Farmacêutica, compared to the comparator drug Clexane®, produced by&#xD;
      Sanofi-Aventis, by determining pharmacodynamic activities (including anti FXa and anti-FIIa),&#xD;
      as surrogate markers for their circulating concentrations of the drug.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In addition other pharmacodynamic tests such as Tissue Factor Pathway Inhibitor (TFPI)&#xD;
      activity, as well as the ratio of anti-FXa and anti-FIIa activity will be compared as&#xD;
      secundary obectives.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 28, 2013</start_date>
  <completion_date type="Actual">October 31, 2013</completion_date>
  <primary_completion_date type="Actual">October 31, 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>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</measure>
    <time_frame>The day after admission</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>The day after admission</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Teste</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enoxalow (Heparin, Low-Molecular-Weight) - Blau Farmacêutica S/A.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparador</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Clexane (Heparin, Low-Molecular-Weight)- Sanofi-Aventis</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Heparin, Low-Molecular-Weight</intervention_name>
    <description>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.</description>
    <arm_group_label>Comparador</arm_group_label>
    <arm_group_label>Teste</arm_group_label>
    <other_name>Clexane</other_name>
    <other_name>Enoxalow</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Agree to all the purposes of the study by signing and dating the Informed Consent;&#xD;
&#xD;
          -  Male, aged between 18 and 55 years, clinically healthy;&#xD;
&#xD;
          -  BMI between 18.5 and 30;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participation in clinical trials in the 12 months preceding the trial;&#xD;
&#xD;
          -  Presence of pulmonary, cardiovascular, neurological, endocrine, gastrointestinal,&#xD;
             genitourinary or other systems diseases;&#xD;
&#xD;
          -  Acute disease in the period of 07 days before the beginning of the practical phase&#xD;
             (administration of the drug) of the study;&#xD;
&#xD;
          -  Chronic administration of medications for hypertension, diabetes or any other disease&#xD;
             that requires continuous use of any drug;&#xD;
&#xD;
          -  Hemoglobin &lt;13 g/dL;&#xD;
&#xD;
          -  Continuous use of oral anticoagulants, platelet inhibitors or anti-inflammatory drugs;&#xD;
&#xD;
          -  Use of medications that interact with enoxaparin;&#xD;
&#xD;
          -  History of gastrointestinal bleeding, deep vein thrombosis or pulmonary embolism that&#xD;
             may interfere with the clinical outcome of the study;&#xD;
&#xD;
          -  History of coagulopathy and bleeding diathesis;&#xD;
&#xD;
          -  Presence of changes in physical examination suggestive of coagulation disorders&#xD;
             (bruising, petechiae, or bruising);&#xD;
&#xD;
          -  Body weight &lt; 45 kg or &gt; 100 kg;&#xD;
&#xD;
          -  Absolute platelet count below 100 x 109 / L;&#xD;
&#xD;
          -  History of chronic bleeding;&#xD;
&#xD;
          -  History of acute haemorrhage in the past 30 days;&#xD;
&#xD;
          -  History of sensitivity to mammalian-derived biological products, albumin or any&#xD;
             component of the formulation;&#xD;
&#xD;
          -  History of allergy or Steven Johnson disease;&#xD;
&#xD;
          -  Current or previous history (under 12 months) use of illicit drugs and tobacco;&#xD;
&#xD;
          -  History of alcohol abuse, current or previous (within 12 months);&#xD;
&#xD;
          -  At the discretion of the Principal Investigator of the study.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Márcia Guidone, manager</last_name>
    <role>Study Director</role>
    <affiliation>Blau Farmaceutica S.A.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>LAL Clinica</name>
      <address>
        <city>Valinhos</city>
        <state>Sao Paulo</state>
        <zip>13271-130</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>4082105</PMID>
  </reference>
  <reference>
    <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. doi: 10.1046/j.1365-2125.2003.01904.x.</citation>
    <PMID>12968985</PMID>
  </reference>
  <reference>
    <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.</citation>
  </reference>
  <reference>
    <citation>FDA 2011. Food and Drug Administration. Draft Guidance on Enoxaparin Sodium.</citation>
  </reference>
  <reference>
    <citation>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. Erratum In: J Thromb Haemost. 2007 Jun;5(6):1343.</citation>
    <PMID>17461929</PMID>
  </reference>
  <reference>
    <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. doi: 10.1378/chest.119.1_suppl.64s. No abstract available.</citation>
    <PMID>11157643</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>18716314</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>12856386</PMID>
  </reference>
  <reference>
    <citation>Wannmacher L. Heparinas de baixo peso molecular: evidências que fundamentam indicações. Uso Racional de Medicamentos: Temas Selecionados 2007:4:1-6.</citation>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>September 20, 2012</study_first_submitted>
  <study_first_submitted_qc>September 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>October 27, 2022</last_update_submitted>
  <last_update_submitted_qc>October 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Subjects</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heparin</mesh_term>
    <mesh_term>Heparin, Low-Molecular-Weight</mesh_term>
    <mesh_term>Tinzaparin</mesh_term>
    <mesh_term>Dalteparin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01692171
org study id: ENOBLA0612IV-I
secondary id: Versão 01 datada de 20.06.2012
nct id: NCT01692171
lead sponsor: 
collaborator: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 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
time frame: The day after admission
description: 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.
measure: 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.
time frame: The day after admission
description: 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.
arm group label: Teste
arm group type: Experimental
description: Enoxalow (Heparin, Low-Molecular-Weight) - Blau Farmacêutica S/A.
arm group label: Comparador
arm group type: Active Comparator
description: Clexane (Heparin, Low-Molecular-Weight)- Sanofi-Aventis
intervention type: Drug
intervention name: Heparin, Low-Molecular-Weight
description: 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.
arm group label: Comparador
arm group label: Teste
other name: Clexane
other name: Enoxalow
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Márcia Guidone, manager
role: Study Director
affiliation: Blau Farmaceutica S.A.
facility: 
country: Brazil
citation: 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.
PMID: 4082105
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. doi: 10.1046/j.1365-2125.2003.01904.x.
PMID: 12968985
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.
citation: FDA 2011. Food and Drug Administration. Draft Guidance on Enoxaparin Sodium.
citation: 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. Erratum In: J Thromb Haemost. 2007 Jun;5(6):1343.
PMID: 17461929
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. doi: 10.1378/chest.119.1_suppl.64s. No abstract available.
PMID: 11157643
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.
PMID: 18716314
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.
PMID: 12856386
citation: Wannmacher L. Heparinas de baixo peso molecular: evidências que fundamentam indicações. Uso Racional de Medicamentos: Temas Selecionados 2007:4:1-6.
responsible party type: Sponsor
mesh term: Heparin
mesh term: Heparin, Low-Molecular-Weight
mesh term: Tinzaparin
mesh term: Dalteparin
sharing ipd: Undecided