<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/NCT02232802</url>
  </required_header>
  <id_info>
    <org_study_id>ENOXA/14/2</org_study_id>
    <nct_id>NCT02232802</nct_id>
  </id_info>
  <brief_title>Bioavailability Study of Enoxaparin Sodium Chemi and Clexane s.c.</brief_title>
  <official_title>Comparative, Randomized, Single-dose, 2-way Cross Over Bioavailability Study of Enoxaparin Sodium Chemi (80 mg/0.8mL) and Clexane® (80 mg/0.8mL) s.c. in Healthy Adult Subjects Under Fasting Conditions.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chemi S.p.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chemi S.p.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      -  The primary objective of the trial is to assess the single-dose relative bioavailability&#xD;
           of Chemi Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by&#xD;
           subcutaneous (s.c.) injection, under fasting conditions in healthy volunteers.&#xD;
&#xD;
        -  The secondary objective of the trial is to assess safety and tolerability of Chemi&#xD;
           Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by s.c. injection,&#xD;
           under fasting conditions in healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, randomised, single-dose, 2-way crossover study to determine the&#xD;
      comparative bioavailability of enoxaparin sodium from the Chemi Enoxaparin s.c. (80 mg/0.8mL)&#xD;
      with that from the reference IMP, Clexane® s.c. (80 mg/0.8mL), following single dose&#xD;
      administration in healthy male and female subjects.&#xD;
&#xD;
      Each subject received each treatment over two separate treatment periods under fasting&#xD;
      conditions. Each dosing day for male subjects will be separated by a washout period of at&#xD;
      least 7 days. The study comprised a pre-study screen (within 14 days of the first dose),&#xD;
      followed by 2 Treatment Periods (1 and 2). During each treatment period, subjects will reside&#xD;
      at Simbec from the evening before dosing (Day 1), until at least 36 h post dose (evening of&#xD;
      Day 2). On admission (Day -1), subjects will provide a urine sample for a drugs of abuse&#xD;
      screen; this sample will also be tested to confirm a negative pregnancy result in female&#xD;
      volunteers.&#xD;
&#xD;
      A single dose of the randomised treatment will be given on the morning of Day 1 following an&#xD;
      overnight fast and blood PK/PD samples collected from pre-dose up to 36 h post dose (14&#xD;
      samples). Safety will also be evaluated at specified times throughout the study.&#xD;
&#xD;
      The post study visit will be conducted on Day 2 (36 h post-dose) of Treatment Period 2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 4, 2014</start_date>
  <completion_date type="Actual">December 5, 2014</completion_date>
  <primary_completion_date type="Actual">December 5, 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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax (Anti-FXa and Anti-FIIa)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Cmax is the maximum measured plasma activity/concentration. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-t (Anti-FXa and Anti-FIIa)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII). thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa).&#xD;
As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-inf (Anti-FXa and Anti-FIIa)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax (Anti-FXa and Anti-FIIa)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Tmax is the time to Cmax. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity. Results are presented as derived plasma PK parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lambda Zeta (Anti-FXa and Anti-FIIa)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.&#xD;
Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (Anti-FXa and Anti-FIIa)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmin (Anti-FXa and Anti-FIIa)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Tmin is the time of Cmin. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC%ex (Anti-FXa and Anti-FIIa)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.&#xD;
Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity. Results are presented as derived plasma PK parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin (Anti-FXa and Anti-FIIa)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Cmin is the minimum plasma activity/concentration. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (Tissue Factor Pathway Inhibitor, TFPI)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Cmax is the maximum measured plasma activity/concentration. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (Anti-FXa/Anti-FIIa Ratio)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Cmax is the maximum measured plasma activity/concentration. The ratio of anti-FXa/anti-FIIa activity was calculated for each parameter. Reults are presented as derived ratio of PK parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-t (Derived Thrombin Generation)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.&#xD;
Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin (Derived Thrombin Generation)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample.&#xD;
Cmin is the minimum plasma activity/concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmin (Derived Thrombin Generation)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample. Tmin is the time of Cmin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-t (Tissue Factor Pathway Inhibitor, TFPI)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-inf (Tissue Factor Pathway Inhibitor, TFPI)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax (Tissue Factor Pathway Inhibitor, TFPI)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Tmax is the time to Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin (Tissue Factor Pathway Inhibitor, TFPI)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Cmin is the minimum plasma activity/concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmin (Tissue Factor Pathway Inhibitor, TFPI)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Tmin is the time of Cmin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2 (Tissue Factor Pathway Inhibitor, TFPI)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lambda Zeta (Tissue Factor Pathway Inhibitor, TFPI)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI)[5], which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC%ex (Tissue Factor Pathway Inhibitor, TFPI)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>Enoxaparin also release tissue factor pathway inhibitor (TFPI)[5], which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-t (Anti-FXa/Anti-FIIa Ratio)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-inf (Anti-FXa/Anti-FIIa Ratio)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2 (Anti-FXa/Anti-FIIa Ratio)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin (Anti-FXa/Anti-FIIa Ratio)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Cmin is the minimun plasma activity/concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmin (Anti-FXa/Anti-FIIa Ratio)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Tmin is the time of Cmin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC%ex (Anti-FXa/Anti-FIIa Ratio)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax (Anti-FXa/Anti-FIIa Ratio)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Tmax is the time to Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lambda Zeta (Anti-FXa/Anti-FIIa Ratio)</measure>
    <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
    <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Enoxaparin Sodium is Administered to Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Enoxaparin Sodium Chemi</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clexane</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin Sodium</intervention_name>
    <description>comparison of bioavailability of generic Enoxaparin Sodium and Clexane</description>
    <arm_group_label>Enoxaparin Sodium Chemi</arm_group_label>
    <other_name>Clexane</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin Sodium</intervention_name>
    <description>comparison of bioavailability of generic Enoxaparin Sodium and Clexane</description>
    <arm_group_label>Clexane</arm_group_label>
    <other_name>generic Enoxaparin Sodium</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male or female volunteer between 18 and 55 years of age.&#xD;
&#xD;
          -  Subject with a BMI of 18-30 (Body Mass Index = Body weight (kg) / [Height (m)]2)&#xD;
&#xD;
          -  Subject with no clinically significant abnormal serum biochemistry, haematology,&#xD;
             coagulation factors and urine examination values within 14 days of the first dose.&#xD;
&#xD;
          -  Subject with no clinically significant abnormalities in 12-lead electrocardiogram&#xD;
             (ECG) and vital signs determined within 14 days of the first dose.&#xD;
&#xD;
          -  Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface&#xD;
             antigen (HbsAg) and hepatitis C virus antibody (HCV) results.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject with hypersensitivity or idiosyncratic reaction to enoxaparin and/or low&#xD;
             molecular weight heparins, and/or pork products.&#xD;
&#xD;
          -  Subject with a relevant history or presence of significant cardiovascular, pulmonary,&#xD;
             hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,&#xD;
             neurologic, or psychiatric disease. Or with history or presence of alcoholism or drug&#xD;
             abuse;&#xD;
&#xD;
          -  Subject with clinically relevant abnormal physical findings or clinically relevant&#xD;
             abnormal laboratory values indicative of physical illness;&#xD;
&#xD;
          -  Female subject who is pregnant or lactating&#xD;
&#xD;
          -  Female subject with weight &lt; 45 kg or male subject with weight &lt; 57 kg.&#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>Paolo Bettica, MD</last_name>
    <role>Study Director</role>
    <affiliation>Italfarmaco S.p.A.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Simbec Research Ltd</name>
      <address>
        <city>Merthyr Tydfil</city>
        <zip>CF48 4DR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 3, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <results_first_submitted>September 7, 2020</results_first_submitted>
  <results_first_submitted_qc>October 19, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 20, 2020</results_first_posted>
  <last_update_submitted>October 19, 2020</last_update_submitted>
  <last_update_submitted_qc>October 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enoxaparin</mesh_term>
    <mesh_term>Enoxaparin sodium</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Forty-seven (47) subjects (23 male and 24 female) were enrolled in the study. The subjects were selected from a large panel who offered their services as healthy volunteers for the purpose of undertaking REC and Regulatory Authority-approved studies on drug safety, absorption and disposition.</recruitment_details>
      <pre_assignment_details>The study comprised a screening visit and 2 treatment periods. Only two doses were scheduled to be administered: first dose (period 1) - wash out (at least 7 days) - 2nd dose (period 2) - wash out period (at least 7 days). Each treatment period was of 2 days duration. Screening assessments: from Day -14 to Day -1.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Test IMP - Reference IMP</title>
          <description>These patients reveiced the following sequence:&#xD;
Test IMP: A single-dose of 80mg/0.8 mL Chemi Enoxaparin. Reference IMP: A single-dose of 80mg/0.8 mL Clexane® Each dose was administered s.c. into the left or right side of the abdomen (alternating sides with treatment period).&#xD;
Each dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection.&#xD;
Subjects remained in an upright position whilst receiving each dose and for 4 h afterwards.&#xD;
There were at least 7 days between each dose administration for males and female subjects of nonchildbearing potential. Female subjects of child bearing potential underwent a washout period of approximately 28 days.</description>
        </group>
        <group group_id="P2">
          <title>Reference IMP - Test IMP</title>
          <description>These patients reveiced the following sequence:&#xD;
Reference IMP: A single-dose of 80mg/0.8 mL Clexane® Test IMP: A single-dose of 80mg/0.8 mL Chemi Enoxaparin. Each dose was administered s.c. into the left or right side of the abdomen (alternating sides with treatment period).&#xD;
Each dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection.&#xD;
Subjects remained in an upright position whilst receiving each dose and for 4 h afterwards.&#xD;
There were at least 7 days between each dose administration for males and female subjects of nonchildbearing potential.&#xD;
Female subjects of child bearing potential underwent a washout period of approximately 28 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Sponsor request</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Washout</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Test IMP - Reference IMP</title>
          <description>These patients reveiced the following sequence:&#xD;
Test IMP: A single-dose of 80mg/0.8 mL Chemi Enoxaparin. Reference IMP: A single-dose of 80mg/0.8 mL Clexane® Each dose was administered s.c. into the left or right side of the abdomen (alternating sides with treatment period).&#xD;
Each dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection.&#xD;
Subjects remained in an upright position whilst receiving each dose and for 4 h afterwards.&#xD;
There were at least 7 days between each dose administration for males and female subjects of nonchildbearing potential. Female subjects of child bearing potential underwent a washout period of approximately 28 days.</description>
        </group>
        <group group_id="B2">
          <title>Reference IMP - Test IMP</title>
          <description>These patients reveiced the following sequence:&#xD;
Reference IMP: A single-dose of 80mg/0.8 mL Clexane® Test IMP: A single-dose of 80mg/0.8 mL Chemi Enoxaparin. Each dose was administered s.c. into the left or right side of the abdomen (alternating sides with treatment period).&#xD;
Each dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection.&#xD;
Subjects remained in an upright position whilst receiving each dose and for 4 h afterwards.&#xD;
There were at least 7 days between each dose administration for males and female subjects of nonchildbearing potential.&#xD;
Female subjects of child bearing potential underwent a washout period of approximately 28 days.</description>
        </group>
        <group group_id="B3">
          <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="24"/>
            <count group_id="B2" value="23"/>
            <count group_id="B3" value="47"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cmax (Anti-FXa and Anti-FIIa)</title>
        <description>Cmax is the maximum measured plasma activity/concentration. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax (Anti-FXa and Anti-FIIa)</title>
          <description>Cmax is the maximum measured plasma activity/concentration. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
          <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anti-FXa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8593" spread="0.18056"/>
                    <measurement group_id="O2" value="0.8698" spread="0.20921"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anti-thrombin/factor IIa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1187" spread="0.03451"/>
                    <measurement group_id="O2" value="0.1296" spread="0.03713"/>
                  </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>
            <groups_desc>Statistical comparison for Anti-FXa</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Following logarithmic transformation, Cmax values were subjected to an analysis of variance (ANOVA), including fixed effects for sequence, period, treatment and subject nested within sequence.</non_inferiority_desc>
            <param_type>least square mean difference ratio</param_type>
            <param_value>99.42</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>96.28</ci_lower_limit>
            <ci_upper_limit>102.65</ci_upper_limit>
            <estimate_desc>Geometric least square means are being compared.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical comparison on Anti-FIIa</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Following logarithmic transformation, Cmax was subjected to an analysis of variance (ANOVA), including fixed effects for sequence, period, treatment and subject nested within sequence</non_inferiority_desc>
            <param_type>least square mean difference ratio</param_type>
            <param_value>91.55</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>86.65</ci_lower_limit>
            <ci_upper_limit>96.73</ci_upper_limit>
            <estimate_desc>Geometric least square means are being compared.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUC0-t (Anti-FXa and Anti-FIIa)</title>
        <description>AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII). thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa).&#xD;
As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-t (Anti-FXa and Anti-FIIa)</title>
          <description>AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII). thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa).&#xD;
As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
          <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>h*IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anti-FXa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.6259" spread="1.68590"/>
                    <measurement group_id="O2" value="9.3927" spread="1.83943"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anti-FIIa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0234" spread="0.28817"/>
                    <measurement group_id="O2" value="1.1097" spread="0.31668"/>
                  </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>
            <groups_desc>Anti-FXa statistical comparison</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Following logarithmic transformation, AUC0-t values were subjected to an analysis of variance (ANOVA), including fixed effects for sequence, period, treatment and subject nested within sequence</non_inferiority_desc>
            <param_type>least square mean difference ratio</param_type>
            <param_value>102.89</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>100.67</ci_lower_limit>
            <ci_upper_limit>105.15</ci_upper_limit>
            <estimate_desc>Geometric least square means are being compared.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Anti-FIIa comparison</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Following logarithmic transformation, AUC0-t values were subjected to an analysis of variance (ANOVA), including fixed effects for sequence, period, treatment and subject nested within sequence.</non_inferiority_desc>
            <param_type>least square mean difference ratio</param_type>
            <param_value>92.37</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>87.72</ci_lower_limit>
            <ci_upper_limit>97.25</ci_upper_limit>
            <estimate_desc>Geometric least square means are being compared.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-inf (Anti-FXa and Anti-FIIa)</title>
        <description>AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-inf (Anti-FXa and Anti-FIIa)</title>
          <description>AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
          <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>h*IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anti-FXa</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.2789" spread="1.71377"/>
                    <measurement group_id="O2" value="9.9197" spread="1.86143"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anti-FIIa</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1489" spread="0.29243"/>
                    <measurement group_id="O2" value="1.2926" spread="0.40401"/>
                  </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>
            <groups_desc>Anti-FXA comparison</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Following logarithmic transformation, AUC0-inf values were subjected to an analysis of variance (ANOVA), including fixed effects for sequence, period, treatment and subject nested within sequence</non_inferiority_desc>
            <param_type>least square mean ratio</param_type>
            <param_value>104.26</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>101.68</ci_lower_limit>
            <ci_upper_limit>106.9</ci_upper_limit>
            <estimate_desc>Geometric least square means are being compared.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Anti-FIIa comparison</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Following logarithmic transformation, AUC0-inf values were subjected to an analysis of variance (ANOVA), including fixed effects for sequence, period, treatment and subject nested within sequence</non_inferiority_desc>
            <param_type>least square mean ratio</param_type>
            <param_value>90.44</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>85.38</ci_lower_limit>
            <ci_upper_limit>95.8</ci_upper_limit>
            <estimate_desc>Geometric least square means are being compared.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax (Anti-FXa and Anti-FIIa)</title>
        <description>Tmax is the time to Cmax. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity. Results are presented as derived plasma PK parameters.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax (Anti-FXa and Anti-FIIa)</title>
          <description>Tmax is the time to Cmax. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity. Results are presented as derived plasma PK parameters.</description>
          <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anti-FXa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0000" lower_limit="2.000" upper_limit="6.000"/>
                    <measurement group_id="O2" value="4.0000" lower_limit="3.000" upper_limit="6.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anti-FIIa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0000" lower_limit="2.000" upper_limit="6.000"/>
                    <measurement group_id="O2" value="4.0000" lower_limit="3.000" upper_limit="16.000"/>
                  </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>
            <groups_desc>Anti-FXa comparison</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>An assessment of tmax was performed using the Wilcoxon matched pairs test. In addition, a 95 % non-parametric CI was constructed for the median difference in tmax based on the method of Campbell and Gardner.</non_inferiority_desc>
            <p_value>0.7642</p_value>
            <p_value_desc>An assessment of tmax was performed using the Wilcoxon matched pairs test. In addition, a 95 % non-parametric CI was constructed for the median difference in tmax based on the method of Campbell and Gardner.</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>least square mean ratio</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.5</ci_lower_limit>
            <ci_upper_limit>0.5</ci_upper_limit>
            <estimate_desc>Geometric least square means are being compared.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Anti-FIIa comparison</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>An assessment of tmax was performed using the Wilcoxon matched pairs test. In addition, a 95 % non-parametric CI was constructed for the median difference in tmax based on the method of Campbell and Gardner.</non_inferiority_desc>
            <p_value>0.9464</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>least square mean ratio</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.5</ci_lower_limit>
            <ci_upper_limit>0.5</ci_upper_limit>
            <estimate_desc>Geometric least square means are being compared.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lambda Zeta (Anti-FXa and Anti-FIIa)</title>
        <description>Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.&#xD;
Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Lambda Zeta (Anti-FXa and Anti-FIIa)</title>
          <description>Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.&#xD;
Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
          <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>1/hour</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anti-FXa</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0962" spread="0.04251"/>
                    <measurement group_id="O2" value="0.1133" spread="0.04337"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anti-IIa</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2111" spread="0.10435"/>
                    <measurement group_id="O2" value="0.1938" spread="0.11612"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>t1/2 (Anti-FXa and Anti-FIIa)</title>
        <description>T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>t1/2 (Anti-FXa and Anti-FIIa)</title>
          <description>T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
          <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anti-FXa</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.4757" spread="3.22737"/>
                    <measurement group_id="O2" value="6.9507" spread="2.42567"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anti-FIIa</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6214" spread="2.97971"/>
                    <measurement group_id="O2" value="6.5045" spread="8.67539"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmin (Anti-FXa and Anti-FIIa)</title>
        <description>Tmin is the time of Cmin. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Tmin (Anti-FXa and Anti-FIIa)</title>
          <description>Tmin is the time of Cmin. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
          <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anti-FXa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.000"/>
                    <measurement group_id="O2" value="0.00" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anti-FIIa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.18" spread="8.538"/>
                    <measurement group_id="O2" value="6.91" spread="12.211"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC%ex (Anti-FXa and Anti-FIIa)</title>
        <description>AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.&#xD;
Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity. Results are presented as derived plasma PK parameters.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC%ex (Anti-FXa and Anti-FIIa)</title>
          <description>AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.&#xD;
Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.&#xD;
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity. Results are presented as derived plasma PK parameters.</description>
          <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>percentage of total value of AUC</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anti-FXa</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4515" spread="2.68130"/>
                    <measurement group_id="O2" value="4.9683" spread="1.80897"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anti-FIIa</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.0593" spread="7.68842"/>
                    <measurement group_id="O2" value="12.0906" spread="9.02925"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmin (Anti-FXa and Anti-FIIa)</title>
        <description>Cmin is the minimum plasma activity/concentration. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Cmin (Anti-FXa and Anti-FIIa)</title>
          <description>Cmin is the minimum plasma activity/concentration. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.</description>
          <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anti-FXa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.0000"/>
                    <measurement group_id="O2" value="0.000" spread="0.0000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anti-FIIa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.002" spread="0.0044"/>
                    <measurement group_id="O2" value="0.002" spread="0.0042"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax (Tissue Factor Pathway Inhibitor, TFPI)</title>
        <description>Cmax is the maximum measured plasma activity/concentration. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax (Tissue Factor Pathway Inhibitor, TFPI)</title>
          <description>Cmax is the maximum measured plasma activity/concentration. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.</description>
          <population>PK population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4327" spread="0.35998"/>
                    <measurement group_id="O2" value="2.3391" spread="0.33903"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Results obtained using a fixed effects ANOVA with fixed effects for sequence, period, treatment and subject nested within sequence</non_inferiority_desc>
            <param_type>Geometric least square mean ratio</param_type>
            <param_value>103.94</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>101.22</ci_lower_limit>
            <ci_upper_limit>106.73</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax (Anti-FXa/Anti-FIIa Ratio)</title>
        <description>Cmax is the maximum measured plasma activity/concentration. The ratio of anti-FXa/anti-FIIa activity was calculated for each parameter. Reults are presented as derived ratio of PK parameters.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax (Anti-FXa/Anti-FIIa Ratio)</title>
          <description>Cmax is the maximum measured plasma activity/concentration. The ratio of anti-FXa/anti-FIIa activity was calculated for each parameter. Reults are presented as derived ratio of PK parameters.</description>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4450" spread="1.04983"/>
                    <measurement group_id="O2" value="6.8546" spread="0.95651"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Results obtained using a fixed effects ANOVA with fixed effects for sequence, period, treatment and subject nested within sequence.</non_inferiority_desc>
            <param_type>Geometric least square mean ratio</param_type>
            <param_value>108.59</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>103.93</ci_lower_limit>
            <ci_upper_limit>113.46</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-t (Derived Thrombin Generation)</title>
        <description>AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.&#xD;
Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-t (Derived Thrombin Generation)</title>
          <description>AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.&#xD;
Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>h*nM</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3731.0710" spread="1375.97298"/>
                    <measurement group_id="O2" value="3597.3375" spread="1104.52084"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Results obtained using a fixed effects ANOVA with fixed effects for sequence, period, treatment and subject nested within sequence.</non_inferiority_desc>
            <param_type>Geometric least square mean ratio</param_type>
            <param_value>102.76</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>97.51</ci_lower_limit>
            <ci_upper_limit>108.28</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmin (Derived Thrombin Generation)</title>
        <description>Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample.&#xD;
Cmin is the minimum plasma activity/concentration.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Cmin (Derived Thrombin Generation)</title>
          <description>Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample.&#xD;
Cmin is the minimum plasma activity/concentration.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>nM</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.534" spread="7.6300"/>
                    <measurement group_id="O2" value="11.543" spread="6.9299"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Results obtained using a fixed effects ANOVA with fixed effects for sequence, period, treatment and subject nested within sequence</non_inferiority_desc>
            <param_type>Geometric least square mean ratio</param_type>
            <param_value>114.91</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>102.29</ci_lower_limit>
            <ci_upper_limit>129.08</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmin (Derived Thrombin Generation)</title>
        <description>Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample. Tmin is the time of Cmin.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Tmin (Derived Thrombin Generation)</title>
          <description>Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample. Tmin is the time of Cmin.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.67" spread="1.136"/>
                    <measurement group_id="O2" value="3.64" spread="0.911"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Results obtained using a fixed effects ANOVA with fixed effects for sequence, period, treatment and subject nested within sequence</non_inferiority_desc>
            <p_value>= 0.8554</p_value>
            <method>ANOVA</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.5</ci_lower_limit>
            <ci_upper_limit>0.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-t (Tissue Factor Pathway Inhibitor, TFPI)</title>
        <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-t (Tissue Factor Pathway Inhibitor, TFPI)</title>
          <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>h*Unit/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.1828" spread="7.91060"/>
                    <measurement group_id="O2" value="55.7851" spread="8.43154"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Results obtained using a fixed effects ANOVA with fixed effects for sequence, period, treatment and subject nested within sequence</non_inferiority_desc>
            <param_type>geometric least square mean ratio</param_type>
            <param_value>100.86</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>99.27</ci_lower_limit>
            <ci_upper_limit>102.47</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-inf (Tissue Factor Pathway Inhibitor, TFPI)</title>
        <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-inf (Tissue Factor Pathway Inhibitor, TFPI)</title>
          <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>h*Unit/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="140.8383" spread="36.06655"/>
                    <measurement group_id="O2" value="173.9833" spread="123.89404"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Results obtained using a fixed effects ANOVA with fixed effects for sequence, period, treatment and subject nested within sequence.</non_inferiority_desc>
            <param_type>geometric least square mean ratio</param_type>
            <param_value>95.13</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>85.7</ci_lower_limit>
            <ci_upper_limit>105.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax (Tissue Factor Pathway Inhibitor, TFPI)</title>
        <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Tmax is the time to Cmax</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax (Tissue Factor Pathway Inhibitor, TFPI)</title>
          <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Tmax is the time to Cmax</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7500" spread="0.83178"/>
                    <measurement group_id="O2" value="1.8068" spread="1.20665"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>An assessment of tmax was performed using the Wilcoxon matched pairs test. In addition, a 95 % nonparametric CI was constructed for the median difference in tmax based on the method of Campbell and Gardner.</non_inferiority_desc>
            <p_value>= 0.6857</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.25</ci_lower_limit>
            <ci_upper_limit>0.5</ci_upper_limit>
            <estimate_desc>Median difference is the difference between median tmax in Test IMP versus Reference IMP arms.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmin (Tissue Factor Pathway Inhibitor, TFPI)</title>
        <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Cmin is the minimum plasma activity/concentration.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Cmin (Tissue Factor Pathway Inhibitor, TFPI)</title>
          <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Cmin is the minimum plasma activity/concentration.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>Unit/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.261" spread="0.2277"/>
                    <measurement group_id="O2" value="1.290" spread="0.2288"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmin (Tissue Factor Pathway Inhibitor, TFPI)</title>
        <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Tmin is the time of Cmin.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Tmin (Tissue Factor Pathway Inhibitor, TFPI)</title>
          <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Tmin is the time of Cmin.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.27" spread="5.275"/>
                    <measurement group_id="O2" value="15.55" spread="6.293"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T1/2 (Tissue Factor Pathway Inhibitor, TFPI)</title>
        <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>T1/2 (Tissue Factor Pathway Inhibitor, TFPI)</title>
          <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.6397" spread="8.66880"/>
                    <measurement group_id="O2" value="57.2439" spread="46.13993"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lambda Zeta (Tissue Factor Pathway Inhibitor, TFPI)</title>
        <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI)[5], which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Lambda Zeta (Tissue Factor Pathway Inhibitor, TFPI)</title>
          <description>Enoxaparin also releases tissue factor pathway inhibitor (TFPI)[5], which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>1/hour</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0172" spread="0.00323"/>
                    <measurement group_id="O2" value="0.0148" spread="0.00440"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC%ex (Tissue Factor Pathway Inhibitor, TFPI)</title>
        <description>Enoxaparin also release tissue factor pathway inhibitor (TFPI)[5], which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC%ex (Tissue Factor Pathway Inhibitor, TFPI)</title>
          <description>Enoxaparin also release tissue factor pathway inhibitor (TFPI)[5], which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.&#xD;
AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>percentage of total AUC</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.9149" spread="5.07416"/>
                    <measurement group_id="O2" value="63.0497" spread="8.81000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-t (Anti-FXa/Anti-FIIa Ratio)</title>
        <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-t (Anti-FXa/Anti-FIIa Ratio)</title>
          <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>h*IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.7836" spread="1.75225"/>
                    <measurement group_id="O2" value="8.7967" spread="1.64043"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Results obtained using a fixed effects ANOVA with fixed effects for sequence, period, treatment and subject nested within sequence</non_inferiority_desc>
            <param_type>Geometric least square mean ratio</param_type>
            <param_value>111.39</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>105.89</ci_lower_limit>
            <ci_upper_limit>117.17</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-inf (Anti-FXa/Anti-FIIa Ratio)</title>
        <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-inf (Anti-FXa/Anti-FIIa Ratio)</title>
          <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>h*IU/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.1620" spread="1.47121"/>
                    <measurement group_id="O2" value="8.2160" spread="1.60673"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Results obtained using a fixed effects ANOVA with fixed effects for sequence, period, treatment and subject nested within sequence</non_inferiority_desc>
            <param_type>Geometric least square mean ratio</param_type>
            <param_value>113.82</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>107.47</ci_lower_limit>
            <ci_upper_limit>120.53</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T1/2 (Anti-FXa/Anti-FIIa Ratio)</title>
        <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>T1/2 (Anti-FXa/Anti-FIIa Ratio)</title>
          <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6595" spread="2.06574"/>
                    <measurement group_id="O2" value="1.9420" spread="1.47865"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmin (Anti-FXa/Anti-FIIa Ratio)</title>
        <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Cmin is the minimun plasma activity/concentration.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Cmin (Anti-FXa/Anti-FIIa Ratio)</title>
          <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Cmin is the minimun plasma activity/concentration.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>UI/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.000"/>
                    <measurement group_id="O2" value="0.000" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmin (Anti-FXa/Anti-FIIa Ratio)</title>
        <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Tmin is the time of Cmin.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Tmin (Anti-FXa/Anti-FIIa Ratio)</title>
          <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Tmin is the time of Cmin.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.000"/>
                    <measurement group_id="O2" value="0.00" spread="0.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC%ex (Anti-FXa/Anti-FIIa Ratio)</title>
        <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC%ex (Anti-FXa/Anti-FIIa Ratio)</title>
          <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>percentage of total AUC</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8078" spread="0.71131"/>
                    <measurement group_id="O2" value="0.6385" spread="0.52118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax (Anti-FXa/Anti-FIIa Ratio)</title>
        <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Tmax is the time to Cmax.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax (Anti-FXa/Anti-FIIa Ratio)</title>
          <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Tmax is the time to Cmax.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9973" spread="0.28432"/>
                    <measurement group_id="O2" value="0.9830" spread="0.24467"/>
                  </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>Equivalence</non_inferiority_type>
            <non_inferiority_desc>An assessment of tmax was performed using the Wilcoxon matched pairs test. In addition, a 95 % nonparametric CI was constructed for the median difference in tmax based on the method of Campbell and Gardner.</non_inferiority_desc>
            <p_value>= 0.9217</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.13</ci_lower_limit>
            <ci_upper_limit>0.13</ci_upper_limit>
            <estimate_desc>Median difference is the difference between median tmax in Test IMP versus Reference IMP arms.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lambda Zeta (Anti-FXa/Anti-FIIa Ratio)</title>
        <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.</description>
        <time_frame>At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)</time_frame>
        <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Enoxaparin Sodium Chemi (Test IMP)</title>
            <description>Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
          <group group_id="O2">
            <title>Clexane (Reference IMP)</title>
            <description>Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).</description>
          </group>
        </group_list>
        <measure>
          <title>Lambda Zeta (Anti-FXa/Anti-FIIa Ratio)</title>
          <description>The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.&#xD;
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.</description>
          <population>PK Population: All subjects who received study medication in both treatment periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.</population>
          <units>1/hour</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6699" spread="0.52191"/>
                    <measurement group_id="O2" value="1.0937" spread="1.82862"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Enoxaparin Sodium Chemi</title>
          <description>Enoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.&#xD;
Enoxaparin Sodium: comparison of bioavailability of generic Enoxaparin Sodium and Clexane</description>
        </group>
        <group group_id="E2">
          <title>Clexane</title>
          <description>Enoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.&#xD;
Enoxaparin Sodium: comparison of bioavailability of generic Enoxaparin Sodium and Clexane</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.0 / 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Fibrous dysplasia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="46"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="46"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 17.0 / 17.1</default_vocab>
        <default_assessment>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="7" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="46"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="46"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="46"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="46"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="46"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="46"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="46"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="46"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="46"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Paolo Bettica, MD</name_or_title>
      <organization>Chemi SpA (Part of Italfarmaco Group)</organization>
      <phone>+39 02 64431</phone>
      <email>p.bettica@italfarmaco.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/NCT02232802
org study id: ENOXA/14/2
nct id: NCT02232802
lead sponsor: 
has dmc: No
-  The primary objective of the trial is to assess the single-dose relative bioavailability
           of Chemi Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by
           subcutaneous (s.c.) injection, under fasting conditions in healthy volunteers.

        -  The secondary objective of the trial is to assess safety and tolerability of Chemi
           Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by s.c. injection,
           under fasting conditions in healthy volunteers.
This is an open-label, randomised, single-dose, 2-way crossover study to determine the
      comparative bioavailability of enoxaparin sodium from the Chemi Enoxaparin s.c. (80 mg/0.8mL)
      with that from the reference IMP, Clexane® s.c. (80 mg/0.8mL), following single dose
      administration in healthy male and female subjects.

      Each subject received each treatment over two separate treatment periods under fasting
      conditions. Each dosing day for male subjects will be separated by a washout period of at
      least 7 days. The study comprised a pre-study screen (within 14 days of the first dose),
      followed by 2 Treatment Periods (1 and 2). During each treatment period, subjects will reside
      at Simbec from the evening before dosing (Day 1), until at least 36 h post dose (evening of
      Day 2). On admission (Day -1), subjects will provide a urine sample for a drugs of abuse
      screen; this sample will also be tested to confirm a negative pregnancy result in female
      volunteers.

      A single dose of the randomised treatment will be given on the morning of Day 1 following an
      overnight fast and blood PK/PD samples collected from pre-dose up to 36 h post dose (14
      samples). Safety will also be evaluated at specified times throughout the study.

      The post study visit will be conducted on Day 2 (36 h post-dose) of Treatment Period 2.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Cmax (Anti-FXa and Anti-FIIa)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Cmax is the maximum measured plasma activity/concentration. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
measure: AUC0-t (Anti-FXa and Anti-FIIa)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII). thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa).
As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
measure: AUC0-inf (Anti-FXa and Anti-FIIa)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
measure: Tmax (Anti-FXa and Anti-FIIa)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Tmax is the time to Cmax. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity. Results are presented as derived plasma PK parameters.
measure: Lambda Zeta (Anti-FXa and Anti-FIIa)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.
Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
measure: t1/2 (Anti-FXa and Anti-FIIa)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
measure: Tmin (Anti-FXa and Anti-FIIa)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Tmin is the time of Cmin. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
measure: AUC%ex (Anti-FXa and Anti-FIIa)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.
Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis.
Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity. Results are presented as derived plasma PK parameters.
measure: Cmin (Anti-FXa and Anti-FIIa)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Cmin is the minimum plasma activity/concentration. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
measure: Cmax (Tissue Factor Pathway Inhibitor, TFPI)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Cmax is the maximum measured plasma activity/concentration. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.
measure: Cmax (Anti-FXa/Anti-FIIa Ratio)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Cmax is the maximum measured plasma activity/concentration. The ratio of anti-FXa/anti-FIIa activity was calculated for each parameter. Reults are presented as derived ratio of PK parameters.
measure: AUC0-t (Derived Thrombin Generation)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.
Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample.
measure: Cmin (Derived Thrombin Generation)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample.
Cmin is the minimum plasma activity/concentration.
measure: Tmin (Derived Thrombin Generation)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample. Tmin is the time of Cmin.
measure: AUC0-t (Tissue Factor Pathway Inhibitor, TFPI)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.
AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.
measure: AUC0-inf (Tissue Factor Pathway Inhibitor, TFPI)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.
AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant.
measure: Tmax (Tissue Factor Pathway Inhibitor, TFPI)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.
Tmax is the time to Cmax
measure: Cmin (Tissue Factor Pathway Inhibitor, TFPI)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.
Cmin is the minimum plasma activity/concentration.
measure: Tmin (Tissue Factor Pathway Inhibitor, TFPI)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.
Tmin is the time of Cmin.
measure: T1/2 (Tissue Factor Pathway Inhibitor, TFPI)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.
T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.
measure: Lambda Zeta (Tissue Factor Pathway Inhibitor, TFPI)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Enoxaparin also releases tissue factor pathway inhibitor (TFPI)[5], which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.
measure: AUC%ex (Tissue Factor Pathway Inhibitor, TFPI)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: Enoxaparin also release tissue factor pathway inhibitor (TFPI)[5], which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.
AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.
measure: AUC0-t (Anti-FXa/Anti-FIIa Ratio)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.
measure: AUC0-inf (Anti-FXa/Anti-FIIa Ratio)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant
measure: T1/2 (Anti-FXa/Anti-FIIa Ratio)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.
measure: Cmin (Anti-FXa/Anti-FIIa Ratio)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
Cmin is the minimun plasma activity/concentration.
measure: Tmin (Anti-FXa/Anti-FIIa Ratio)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
Tmin is the time of Cmin.
measure: AUC%ex (Anti-FXa/Anti-FIIa Ratio)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.
measure: Tmax (Anti-FXa/Anti-FIIa Ratio)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
Tmax is the time to Cmax.
measure: Lambda Zeta (Anti-FXa/Anti-FIIa Ratio)
time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
description: The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.
arm group label: Enoxaparin Sodium Chemi
arm group type: Experimental
description: Enoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.
arm group label: Clexane
arm group type: Experimental
description: Enoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.
intervention type: Drug
intervention name: Enoxaparin Sodium
description: comparison of bioavailability of generic Enoxaparin Sodium and Clexane
arm group label: Enoxaparin Sodium Chemi
other name: Clexane
intervention type: Drug
intervention name: Enoxaparin Sodium
description: comparison of bioavailability of generic Enoxaparin Sodium and Clexane
arm group label: Clexane
other name: generic Enoxaparin Sodium
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Paolo Bettica, MD
role: Study Director
affiliation: Italfarmaco S.p.A.
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Enoxaparin
mesh term: Enoxaparin sodium
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 