<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/NCT02185534</url>
  </required_header>
  <id_info>
    <org_study_id>D5130C00131</org_study_id>
    <nct_id>NCT02185534</nct_id>
  </id_info>
  <brief_title>Clopidogrel Bioequivalence Study in Healthy Subjects</brief_title>
  <official_title>An Open-label, Randomised, Three-way Crossover Study in Healthy Subjects to Assess the Bioequivalence of European Source Generic Clopidogrel Tablets and US and Japanese Source Branded Clopidogrel (Plavix®) Tablets.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will be an open-label, randomised, three-way crossover study in healthy male and&#xD;
      female subjects, performed at a single centre. The objective of the study is to assess the&#xD;
      bioequivalence between one test formulation (Clopidogrel 75 mg tablet (commercial blister&#xD;
      from KRKA) and two reference formulations (Clopidogrel 75 mg tablet [Plavix, sourced in US&#xD;
      and Japan]).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study to evaluate the bioequivalence of orally administered European source clopidogrel&#xD;
      tablets and US and Japanese source clopidogrel tablets.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf))</measure>
    <time_frame>0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose</time_frame>
    <description>Comparison of the pharmacokinetic profile in terms of plasma concentration-time curve from time zero extrapolated to infinity, AUC(0-inf), of clopidogrel sourced in Europe and Japan.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of Clopidogrel by Assessment of Observed Maximum Plasma Concentration (Cmax)</measure>
    <time_frame>0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose</time_frame>
    <description>Comparison of the pharmacokinetic profile in terms of observed maximum plasma concentration, taken directly from the individual concentration-time curve, Cmax, of clopidogrel sourced in Europe and the US.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC(0-last))</measure>
    <time_frame>0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose</time_frame>
    <description>Comparison of the pharmacokinetic profile in terms of the area under the plasma concentration-curve from time zero to the time of last quantifiable clopidogrel or SR26334 concentration, AUC(0-last), of clopidogrel sourced in Europe and the US.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">144</enrollment>
  <condition>Bioequivalence, AUC, Cmax, Pharmacokinetics</condition>
  <arm_group>
    <arm_group_label>European clopidogrel tablets, 75 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet (Zyllt, KRKA - test)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Japanese clopidogrel tablets, 75 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi-Aventis, reference)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>US clopidogrel tablets, 75 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clopidogrel</intervention_name>
    <description>European clopidogrel tablets, 75 mg (test) versus Japanese clopidogrel tablets, 75 mg (reference); European clopidogrel tablets, 75 mg (test) versus US clopidogrel tablets, 75 mg (reference)</description>
    <arm_group_label>European clopidogrel tablets, 75 mg</arm_group_label>
    <arm_group_label>Japanese clopidogrel tablets, 75 mg</arm_group_label>
    <arm_group_label>US clopidogrel tablets, 75 mg</arm_group_label>
    <other_name>Zyllt</other_name>
    <other_name>Plavix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and female subjects aged 18 to 55 years with suitable veins for&#xD;
             cannulation or repeated venepuncture.&#xD;
&#xD;
          -  Females must have a negative pregnancy test at screening and on each admission to the&#xD;
             clinical unit, must not be lactating and&#xD;
&#xD;
             • if of non child-bearing potential, confirmed at screening by fulfilling one of the&#xD;
             following criteria:&#xD;
&#xD;
          -  Post-menopausal defined as amenorrhoea for at least 12 months or more following&#xD;
             cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH)&#xD;
             levels in the post-menopausal range.&#xD;
&#xD;
          -  Documentation of irreversible surgical sterilisation by hysterectomy, bilateral&#xD;
             oophorectomy or bilateral salpingectomy but not tubal ligation.&#xD;
&#xD;
             • if of child-bearing potential and are sexually active must use, with their partner,&#xD;
             2 approved methods of highly effective contraception from the time of IMP&#xD;
             administration until 3 months after the last dose of IMP.&#xD;
&#xD;
          -  Have a body mass index between 18,5 and 29.9 kg/m2 inclusive and weigh at least 50 kg&#xD;
             and no more than 100 kg inclusive.&#xD;
&#xD;
          -  Be able to understand, read and speak the German language.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  History of any clinically significant disease or disorder which, in the opinion of the&#xD;
             Investigator, may either put the potential subject at risk because of participation in&#xD;
             the study, or influence the results or the potential subject's ability to participate&#xD;
             in the study.&#xD;
&#xD;
          -  Current smokers or those who have smoked or used nicotine products within the previous&#xD;
             3 months.&#xD;
&#xD;
          -  History of haemophilia, von Willebrand's disease, lupus anticoagulant, or other&#xD;
             diseases/syndromes that can either alter or increase the propensity for bleeding.&#xD;
&#xD;
          -  A personal history of vascular abnormalities including aneurysms; a personal history&#xD;
             of severe haemorrhage, haematemesis, melena, haemoptysis, severe epistaxis, severe&#xD;
             thrombocytopenia, intracranial haemorrhage; or rectal bleeding within 1 year prior to&#xD;
             screening; or history suggestive of peptic ulcer disease; or at the discretion of the&#xD;
             Investigator.&#xD;
&#xD;
          -  Use of aspirin, ibuprofen, NSAIDS, or any other drug known to increase the propensity&#xD;
             for bleeding for 2 weeks before randomisation.&#xD;
      </textblock>
    </criteria>
    <gender>All</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>Rainard Fuhr, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>PAREXEL International GmbH, Berlin</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Glenn Carlson, MD</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca, Wilmington, US</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>July 4, 2014</study_first_submitted>
  <study_first_submitted_qc>July 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <results_first_submitted>September 18, 2015</results_first_submitted>
  <results_first_submitted_qc>October 28, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 30, 2015</results_first_posted>
  <last_update_submitted>May 18, 2016</last_update_submitted>
  <last_update_submitted_qc>May 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Clopidogrel, Zyllt, Plavix, Phase I, Healthy Subjects, Pharmacokinetics, Bioequivalence</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clopidogrel</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants recruited at PAREXEL Early Phase Clinical Unit Berlin, Germany between August 2014 and September 2014.</recruitment_details>
      <pre_assignment_details>84 participants recruited; 144 screened, 60 excluded (59 did not meet inclusion criteria and 1 refused participation)</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>First European, Then Japanese, Then US Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA&#xD;
- test) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 3</description>
        </group>
        <group group_id="P2">
          <title>First European, Then US, Then Japanese Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi-Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 3</description>
        </group>
        <group group_id="P3">
          <title>First Japanese, Then European, Then US Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi-Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 3</description>
        </group>
        <group group_id="P4">
          <title>First Japanese, Then US, Then European Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi-Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 3</description>
        </group>
        <group group_id="P5">
          <title>First US, Then European, Then Japanese Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 1, a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 3</description>
        </group>
        <group group_id="P6">
          <title>First US, Then Japanese, Then European Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 3</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="14"/>
                <participants group_id="P5" count="14"/>
                <participants group_id="P6" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="13"/>
                <participants group_id="P5" count="14"/>
                <participants group_id="P6" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>First Washout Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="13"/>
                <participants group_id="P5" count="14"/>
                <participants group_id="P6" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="13"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Second Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="13"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="13"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Second Washout Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="13"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="13"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Third Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="13"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="13"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The overall number of baseline participants is 84, as it comprised all randomized subjects, although one subject withdrew consent prior to the first dose. Thus the safety population includes 83 subjects only.</population>
      <group_list>
        <group group_id="B1">
          <title>First European, Then Japanese, Then US Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA&#xD;
- test) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 3</description>
        </group>
        <group group_id="B2">
          <title>First European, Then US, Then Japanese Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi-Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 3</description>
        </group>
        <group group_id="B3">
          <title>First Japanese, Then European, Then US Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi-Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 3</description>
        </group>
        <group group_id="B4">
          <title>First Japanese, Then US, Then European Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi-Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 3</description>
        </group>
        <group group_id="B5">
          <title>First US, Then European, Then Japanese Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 1, a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 3</description>
        </group>
        <group group_id="B6">
          <title>First US, Then Japanese, Then European Clopidogrel</title>
          <description>A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 3</description>
        </group>
        <group group_id="B7">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="14"/>
            <count group_id="B4" value="14"/>
            <count group_id="B5" value="14"/>
            <count group_id="B6" value="14"/>
            <count group_id="B7" value="84"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33" spread="9"/>
                    <measurement group_id="B2" value="37" spread="11"/>
                    <measurement group_id="B3" value="36" spread="10"/>
                    <measurement group_id="B4" value="35" spread="8"/>
                    <measurement group_id="B5" value="34" spread="9"/>
                    <measurement group_id="B6" value="36" spread="11"/>
                    <measurement group_id="B7" value="35" spread="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="10"/>
                    <measurement group_id="B7" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="12"/>
                    <measurement group_id="B6" value="13"/>
                    <measurement group_id="B7" value="79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="12"/>
                    <measurement group_id="B6" value="13"/>
                    <measurement group_id="B7" value="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI (Body Mass Index)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.7" spread="3.1"/>
                    <measurement group_id="B2" value="24.7" spread="3.5"/>
                    <measurement group_id="B3" value="23.4" spread="2.9"/>
                    <measurement group_id="B4" value="24.1" spread="2.7"/>
                    <measurement group_id="B5" value="23.0" spread="3.1"/>
                    <measurement group_id="B6" value="23.9" spread="3.1"/>
                    <measurement group_id="B7" value="23.8" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf))</title>
        <description>Comparison of the pharmacokinetic profile in terms of plasma concentration-time curve from time zero extrapolated to infinity, AUC(0-inf), of clopidogrel sourced in Europe and Japan.</description>
        <time_frame>0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose</time_frame>
        <population>The pharmacokinetic population consisted of 79 subjects, i.e. all subjects in the safety population for whom AUC(0-last) and Cmax could be calculated for clopidogrel for the test treatment (European) and at least one of the reference treatments (Japanese, US). AUC(0-inf) could not be reliably calculated for many of these subjects.</population>
        <group_list>
          <group group_id="O1">
            <title>European Clopidogrel Tablets, 75 mg</title>
            <description>Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet Eu(Zyllt, KRKA - test)</description>
          </group>
          <group group_id="O2">
            <title>Japanese Clopidogrel Tablets, 75 mg</title>
            <description>Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi- Aventis, reference)</description>
          </group>
          <group group_id="O3">
            <title>US Clopidogrel Tablets, 75 mg</title>
            <description>Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf))</title>
          <description>Comparison of the pharmacokinetic profile in terms of plasma concentration-time curve from time zero extrapolated to infinity, AUC(0-inf), of clopidogrel sourced in Europe and Japan.</description>
          <population>The pharmacokinetic population consisted of 79 subjects, i.e. all subjects in the safety population for whom AUC(0-last) and Cmax could be calculated for clopidogrel for the test treatment (European) and at least one of the reference treatments (Japanese, US). AUC(0-inf) could not be reliably calculated for many of these subjects.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="45"/>
                <count group_id="O3" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.05" spread="139.0"/>
                    <measurement group_id="O2" value="0.992" spread="117.9"/>
                    <measurement group_id="O3" value="1.09" spread="106.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The analysis was conducted using an analysis of variance (ANOVA) including fixed effects for treatment, sequence, period and subject within sequence. All pharmacokinetic parameters were log-transformed prior to analysis. Bioequivalence was concluded, when the 90% confidence interval (CI) for the geometric LS mean ratios were fully contained within the predefined equivalence limits of 0.80 to 1.25</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>104.43</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>92.27</ci_lower_limit>
            <ci_upper_limit>118.19</ci_upper_limit>
            <estimate_desc>Geometric mean ratio is calculated as A/B, where A= European clopidogrel and B=Japanese clopidogrel</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The analysis was conducted using an analysis of variance (ANOVA) including fixed effects for treatment, sequence, period and subject within sequence. All pharmacokinetic parameters were log-transformed prior to analysis. Bioequivalence was concluded, when the 90% confidence interval (CI) for the geometric LS mean ratios were fully contained within the predefined equivalence limits of 0.80 to 1.25</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Geometric mean ratio is calculated as A/C, where A= European clopidogrel and C=US clopidogrel</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>97.19</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>81.12</ci_lower_limit>
            <ci_upper_limit>116.45</ci_upper_limit>
            <estimate_desc>Geometric mean ratio is calculated as A/C, where A= European clopidogrel and C=US clopidogrel</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics of Clopidogrel by Assessment of Observed Maximum Plasma Concentration (Cmax)</title>
        <description>Comparison of the pharmacokinetic profile in terms of observed maximum plasma concentration, taken directly from the individual concentration-time curve, Cmax, of clopidogrel sourced in Europe and the US.</description>
        <time_frame>0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose</time_frame>
        <population>The pharmacokinetic population consisted of 79 subjects, i.e. all subjects in the safety population for whom AUC(0-last) and Cmax could be calculated for clopidogrel for the test treatment (European) and at least one of the reference treatments (Japanese, US)</population>
        <group_list>
          <group group_id="O1">
            <title>European Clopidogrel Tablets, 75 mg</title>
            <description>Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet Eu(Zyllt, KRKA - test)</description>
          </group>
          <group group_id="O2">
            <title>Japanese Clopidogrel Tablets, 75 mg</title>
            <description>Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi- Aventis, reference)</description>
          </group>
          <group group_id="O3">
            <title>US Clopidogrel Tablets, 75 mg</title>
            <description>Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics of Clopidogrel by Assessment of Observed Maximum Plasma Concentration (Cmax)</title>
          <description>Comparison of the pharmacokinetic profile in terms of observed maximum plasma concentration, taken directly from the individual concentration-time curve, Cmax, of clopidogrel sourced in Europe and the US.</description>
          <population>The pharmacokinetic population consisted of 79 subjects, i.e. all subjects in the safety population for whom AUC(0-last) and Cmax could be calculated for clopidogrel for the test treatment (European) and at least one of the reference treatments (Japanese, US)</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="79"/>
                <count group_id="O2" value="79"/>
                <count group_id="O3" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.551" spread="122.6"/>
                    <measurement group_id="O2" value="0.511" spread="150.6"/>
                    <measurement group_id="O3" value="0.521" spread="122.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The analysis was conducted using an analysis of variance (ANOVA) including fixed effects for treatment, sequence, period and subject within sequence. All pharmacokinetic parameters were log-transformed prior to analysis. Bioequivalence was concluded, when the 90% confidence interval (CI) for the geometric LS mean ratios were fully contained within the predefined equivalence limits of 0.80 to 1.25.</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>108.06</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>95.46</ci_lower_limit>
            <ci_upper_limit>122.33</ci_upper_limit>
            <estimate_desc>Geometric mean ratio is calculated as A/B, where A= European clopidogrel and B=Japanese clopidogrel</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The analysis was conducted using an analysis of variance (ANOVA) including fixed effects for treatment, sequence, period and subject within sequence. All pharmacokinetic parameters were log-transformed prior to analysis. Bioequivalence was concluded, when the 90% confidence interval (CI) for the geometric LS mean ratios were fully contained within the predefined equivalence limits of 0.80 to 1.25.</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>105.79</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>95.22</ci_lower_limit>
            <ci_upper_limit>117.53</ci_upper_limit>
            <estimate_desc>Geometric mean ratio is calculated as A/C, where A= European clopidogrel and C=US clopidogrel</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC(0-last))</title>
        <description>Comparison of the pharmacokinetic profile in terms of the area under the plasma concentration-curve from time zero to the time of last quantifiable clopidogrel or SR26334 concentration, AUC(0-last), of clopidogrel sourced in Europe and the US.</description>
        <time_frame>0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose</time_frame>
        <population>The pharmacokinetic population consisted of 79 subjects, i.e. all subjects in the safety population for whom AUC(0-last) and Cmax could be calculated for clopidogrel for the test treatment (European) and at least one of the reference treatments (Japanese, US)</population>
        <group_list>
          <group group_id="O1">
            <title>European Clopidogrel Tablets, 75 mg</title>
            <description>Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet Eu(Zyllt, KRKA - test)</description>
          </group>
          <group group_id="O2">
            <title>Japanese Clopidogrel Tablets, 75 mg</title>
            <description>Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi- Aventis, reference)</description>
          </group>
          <group group_id="O3">
            <title>US Clopidogrel Tablets, 75 mg</title>
            <description>Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC(0-last))</title>
          <description>Comparison of the pharmacokinetic profile in terms of the area under the plasma concentration-curve from time zero to the time of last quantifiable clopidogrel or SR26334 concentration, AUC(0-last), of clopidogrel sourced in Europe and the US.</description>
          <population>The pharmacokinetic population consisted of 79 subjects, i.e. all subjects in the safety population for whom AUC(0-last) and Cmax could be calculated for clopidogrel for the test treatment (European) and at least one of the reference treatments (Japanese, US)</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="79"/>
                <count group_id="O2" value="79"/>
                <count group_id="O3" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.705" spread="114.8"/>
                    <measurement group_id="O2" value="0.751" spread="116.5"/>
                    <measurement group_id="O3" value="0.767" spread="107.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The analysis was conducted using an analysis of variance (ANOVA) including fixed effects for treatment, sequence, period and subject within sequence. All pharmacokinetic parameters were log-transformed prior to analysis. Bioequivalence was concluded, when the 90% confidence interval (CI) for the geometric LS mean ratios were fully contained within the predefined equivalence limits of 0.80 to 1.25.</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>93.94</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>87.12</ci_lower_limit>
            <ci_upper_limit>101.29</ci_upper_limit>
            <estimate_desc>Geometric mean ratio is calculated as A/B, where A= European clopidogrel and B=Japanese clopidogrel</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The analysis was conducted using an analysis of variance (ANOVA) including fixed effects for treatment, sequence, period and subject within sequence. All pharmacokinetic parameters were log-transformed prior to analysis. Bioequivalence was concluded, when the 90% confidence interval (CI) for the geometric LS mean ratios were fully contained within the predefined equivalence limits of 0.80 to 1.25</non_inferiority_desc>
            <param_type>Geometric mean ratio</param_type>
            <param_value>92.03</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>84.91</ci_lower_limit>
            <ci_upper_limit>99.75</ci_upper_limit>
            <estimate_desc>Geometric mean ratio is calculated as A/C, where A= European clopidogrel and C=US clopidogrel</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From screening until follow-up, i.e. up to 7 weeks after the first dose.</time_frame>
      <desc>Adverse events (AEs) were assigned to the treatment after which they occurred:&#xD;
Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets</desc>
      <group_list>
        <group group_id="E1">
          <title>European Clopidogrel Tablets, 75 mg</title>
          <description>Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet Eu(Zyllt, KRKA - test)</description>
        </group>
        <group group_id="E2">
          <title>Japanese Clopidogrel Tablets, 75 mg</title>
          <description>Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi- Aventis, reference)</description>
        </group>
        <group group_id="E3">
          <title>US Clopidogrel Tablets, 75 mg</title>
          <description>Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)</description>
        </group>
        <group group_id="E4">
          <title>Total Number of Participants</title>
          <description>total number of subjects exposed to any treatment</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_vocab>MedDRA version 17.0.</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="81"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="80"/>
                <counts group_id="E3" subjects_affected="22" subjects_at_risk="82"/>
                <counts group_id="E4" subjects_affected="38" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="81"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="82"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter Site Pain</sub_title>
                <description>includes Administration Site Conditions</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="80"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Catheter Site Inflammation</sub_title>
                <description>includes Administration site Conditions</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <description>includes Administrations Site Conditions</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="81"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="82"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="81"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="19" subjects_affected="16" subjects_at_risk="81"/>
                <counts group_id="E2" events="17" subjects_affected="15" subjects_at_risk="80"/>
                <counts group_id="E3" events="20" subjects_affected="16" subjects_at_risk="82"/>
                <counts group_id="E4" events="56" subjects_affected="29" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="82"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="81"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="82"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="83"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="81"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="82"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="83"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>If a publication (e.g., in a scientific journal) based on the results of this study is envisaged, approval from AstraZeneca will be obtained and a draft manuscript will be submitted to AstraZeneca for scrutiny and comment. The choice of conduit will be mutually agreed on by the Principal Investigator and AstraZeneca.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Brilinta Global Clinical Leader</name_or_title>
      <organization>AstraZeneca</organization>
      <phone>+46 31 776 1000</phone>
      <email>ClinicalTrialTransparency@astrazeneca.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02185534
org study id: D5130C00131
nct id: NCT02185534
lead sponsor: 
has dmc: No
This study will be an open-label, randomised, three-way crossover study in healthy male and
      female subjects, performed at a single centre. The objective of the study is to assess the
      bioequivalence between one test formulation (Clopidogrel 75 mg tablet (commercial blister
      from KRKA) and two reference formulations (Clopidogrel 75 mg tablet [Plavix, sourced in US
      and Japan]).
Study to evaluate the bioequivalence of orally administered European source clopidogrel
      tablets and US and Japanese source clopidogrel tablets.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf))
time frame: 0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose
description: Comparison of the pharmacokinetic profile in terms of plasma concentration-time curve from time zero extrapolated to infinity, AUC(0-inf), of clopidogrel sourced in Europe and Japan.
measure: Pharmacokinetics of Clopidogrel by Assessment of Observed Maximum Plasma Concentration (Cmax)
time frame: 0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose
description: Comparison of the pharmacokinetic profile in terms of observed maximum plasma concentration, taken directly from the individual concentration-time curve, Cmax, of clopidogrel sourced in Europe and the US.
measure: Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC(0-last))
time frame: 0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose
description: Comparison of the pharmacokinetic profile in terms of the area under the plasma concentration-curve from time zero to the time of last quantifiable clopidogrel or SR26334 concentration, AUC(0-last), of clopidogrel sourced in Europe and the US.
arm group label: European clopidogrel tablets, 75 mg
arm group type: Experimental
description: Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet (Zyllt, KRKA - test)
arm group label: Japanese clopidogrel tablets, 75 mg
arm group type: Active Comparator
description: Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi-Aventis, reference)
arm group label: US clopidogrel tablets, 75 mg
arm group type: Active Comparator
description: Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)
intervention type: Drug
intervention name: Clopidogrel
description: European clopidogrel tablets, 75 mg (test) versus Japanese clopidogrel tablets, 75 mg (reference); European clopidogrel tablets, 75 mg (test) versus US clopidogrel tablets, 75 mg (reference)
arm group label: European clopidogrel tablets, 75 mg
arm group label: Japanese clopidogrel tablets, 75 mg
arm group label: US clopidogrel tablets, 75 mg
other name: Zyllt
other name: Plavix
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Rainard Fuhr, Dr. med.
role: Principal Investigator
affiliation: PAREXEL International GmbH, Berlin
last name: Glenn Carlson, MD
role: Study Director
affiliation: AstraZeneca, Wilmington, US
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Clopidogrel
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 