A Single-Dose Trial to Examine the Within Subject Variability of Clexane® in Healthy Adults Under Fasting Conditions

• Sponsor: Chemi S.p.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02081950
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arm: 1

Study Details

Study Description

Brief Summary

Primary: To examine the within subject variability of Clexane (80 mg) in healthy male and female volunteers administered subcutaneously (s.c.) as a single dose, in two periods, under fasting conditions.

Secondary: To monitor safety during the Treatment Periods.

Condition or Disease	Intervention/Treatment	Phase
Clexane is Administered to Healthy Volunteers	Biological: Enoxaparin sodium	Phase 1

Detailed Description

This was a pilot, open-label study to evaluate the PK of enoxaparin following s.c. administrations of 80 mg Clexane, on 2 different occasions, in 14 healthy adult subjects.

The study comprised a Screening Visit and 2 Treatment Periods (1 and 2). Screening (Day -14 to Day -1): Screening assessments were carried out within 14 days before administration of the first dose of Clexane. Eligible subjects were asked to return for Treatment Period 1.

Treatment Periods 1 and 2 (Day 0 to Day 26): Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Final confirmation of eligibility was made prior to dosing during Treatment Period 1. Confirmation of ongoing eligibility was made prior to dosing during Treatment Period 2.

Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). During each Treatment Period, subjects resided at the Clinical Unit. Study drug was administered on the morning of Day 1 following an overnight fast. Pharmacokinetic (PK) samples were collected pre-dose and up to 36 h post-dose (x14 samples) for the measurement of enoxaparin. Safety was also evaluated at specified times throughout the study. There were at least 7 days between each dose administration. The Post-Study Follow-Up was conducted on Day 2 of Treatment Period 2 after completion of the 36 h PK blood sampling and vital sign check.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Single-Dose Study to Examine the Within Subject Variability of Clexane® (80 mg) s.c. in Healthy Adult Subjects Under Fasting Conditions
• Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enoxaparin sodium Enoxaparin sodium (80mg) is administered subcutaneously as a single dose, in 2 periods.	Biological: Enoxaparin sodium; comparison of 2 different administration of drug; Other Names: Clexane

Outcome Measures

Primary Outcome Measures

1. Anti-FXa Cmax [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   Enoxaparin exerts its anticoagulant 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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.

2. Anti-FXa AUC0-t [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. AUC0-t is the area under the plasma concentration versus time curve from the time of dosing to the time (t) of the last observed value.

3. Anti-FXa AUC0-inf [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. AUC0-inf is the AUC extrapolated to infinity from dosing time, based on the last observed value.

4. Anti-FIIa Cmax [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.

5. Anti-FIIA AUC0-t [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. AUC0-t is the area under the plasma concentration versus time curve from the time of dosing to the time (t) of the last observed value.

6. Anti-FIIA AUC0-inf [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. AUC0-inf is the AUC extrapolated to infinity from dosing time, based on the last observed value.

Secondary Outcome Measures

1. Anti-FXa Tmax [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. tmax is the time to Cmax.

2. Anti-FXa Lambda Zeta [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration versus time curve.

3. Anti-FXa t1/2 [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. t1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.

4. Anti-FXa Cmin [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Cmin is the minimum plasma activity/concentration.

5. Anti-FXa Tmin [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Tmin is time to Cmin. If the minimum value occurred at >1 time point, tmin was defined as the first time point with this value.

6. Anti-FIIa Tmax [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. tmax is time to Cmax. if the maximum value occurred at >1 time point, tmax was defined as the first time point with this value.

7. Anti-FIIa Lambda Zeta [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration versus time curve.

8. Anti-FIIa t1/2 [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. t1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.

9. Anti-FIIa Cmin [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

   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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Cmin is the minimum plasma activity/concentration.

10. Anti-FIIa Tmin [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. tmin is the time to minimum concentration.

11. Thrombin/FIIa Generation AUC0-t [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin may have the ability to modulate the fibrinolytic process, by virtue of its ability to inhibit FIIa activity and its generation. Thrombin generation test is an integral indicator of the blood clotting system status. This parameter is used for monitoring enoxaparin therapy in patients. AUC0-t is the area under the plasma concentration versus time curve from the time of dosing to the time (t) of the last observed value.

12. Thrombin/FIIa Generation Cmin [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin may have the ability to modulate the fibrinolytic process, by virtue of their ability to inhibit FIIa activity and its generation. Thrombin generation test is an integral indicator of the blood clotting system status. This parameter is used for monitoring enoxaparin therapy in patients. Cmin is the minimum plasma activity/concentration.

13. Thrombin/FIIa Generation Tmin [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin may have the ability to modulate the fibrinolytic process, by virtue of its ability to inhibit FIIa activity and its generation. Thrombin generation test is an integral indicator of the blood clotting system status. This parameter is used for monitoring enoxaparin therapy in patients. Tmin is time to Cmin. If the minimum value occurred at > 1 time-point Tmin was defined as the first time-point with this value.

14. TFPI Cmax [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.

15. TFPI Tmax [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Tmax is the time to Cmax. If the maximum value occurred at > 1 time-point Tmax was defined as the first time-point with this value.

16. TFPI Lambda Zeta [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant 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 versus time curve. The parameter was calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase (e.g. ≥ 3 non-zero plasma concentrations).

17. TFPI T1/2 [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.

18. TFPI AUC0-t [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant 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.

19. TFPI AUC0-inf [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant 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. AUC0-inf was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant.

20. TFPI Tmin [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Tmin is the time of Cmin. If the minimum value occurred at > 1 time-point Tmin was defined as the first time-point with this value.

21. TFPI Cmin [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Cmin is the minimum plasma activity/concentration.

22. Anti-FXa/Anti-FIIa Cmax [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Anti-FXa/anti-FIIa activity Cmax is reported. Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.

23. Anti-FXa/Anti-FIIa AUC0-t [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Anti-FXa/anti-FIIa activity AUC0-t is reported. 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.

24. Anti-FXa/Anti-FIIa AUC0-inf [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Anti-FXa/anti-FIIa activity AUC0-inf is reported. AUC0-inf is the AUC extrapolated to infinity from dosing time, based on the last observed value.

25. Anti-FXa/Anti-FIIa Tmax [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Anti-FXa/anti-FIIa activity Tmax is reported. Tmax is the Time to Cmax. If the maximum value occurred at > 1 time-point Tmax was defined as the first time-point with this value.

26. Anti-FXa/Anti-FIIa Lambda Zeta [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Anti-FXa/anti-FIIa activity lambda zeta is reported. Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase (e.g. ≥ 3 non-zero plasma concentrations).

27. Anti-FXa/Anti-FIIa t1/2 [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Anti-FXa/anti-FIIa activity t1/2 is reported. t1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.

28. Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs [Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.]

    Description of adverse event profile in healthy volunteers after administration of Enoxaparin sodium s.c. as above described.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male or female volunteer between 18 and 55 years of age.

• Female subject of child bearing potential with a negative pregnancy test at the Screening Visit and willing to use 2 effective methods of contraception from Day 1 until 3 months afterwards.

• Subject with no clinically significant abnormal serum biochemistry, haematology, coagulation factors and urine examination values within 14 days of the first dose.

Exclusion Criteria:

• Female subject with weight < 45 kg or male subject with weight < 57 kg.

• Subject with clinically relevant abnormal physical findings which could interfere with the objective of the study.

• Subject with clinically relevant abnormal laboratory values indicative of physical illness; Hemoglobin <13 g/dL; Absolute platelet count below 100 x 109/L.

• Subject with hypersensitivity or idiosyncratic reaction to enoxaparin and/or low molecular weight heparins, and/or pork products.

• Subject with a relevant history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease. In addition, history or presence of: alcoholism or drug abuse within the past year; clotting disorders; gastric or duodenal ulcers; hypertension; retinopathy; deep venous thrombosis; pulmonary embolism; GI bleeding.

• Subject with any clinically significant illness within 4 weeks prior to dosing.

• Subject with recent use of NSAID and/or aspirin (within 4 weeks of first dose) or the use of any pharmacological agents known to significantly induce or inhibit drug-metabolizing enzymes within 30 days of the first dose. No subject may take any antibiotic agent known to interfere with intestinal microflora within 30 days of the first dose. Subjects with any medical condition requiring regular treatment with prescription drugs.

• Subject with recent severe trauma, surgery (eye surgery), and/or lumbar puncture;

• Female subject who was pregnant or lactating.

• Subject who was a vegetarian.

• Subject who, through completion of the study, would have donated in excess of 500 mL of blood and/or plasma within the previous 3 months.

• Subject who regularly consumed excessive amounts of alcohol.

• Subject who consumed excessive amount of caffeine (> 5 cups of coffee or equivalent per day).

• Subject who was a smoker (cigarettes and tobacco-related products), or ex-smoker who had smoked in the 3 months preceding the study. Subjects were tested for urinary cotinine at screening.

• Subjects who could not tolerate venepuncture.

• Inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function).

• Participation in a New Chemical Entity clinical study within the previous 4 months or a marketed drug clinical study within the previous 3 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Simbec Research Ltd	Merthyr Tydfil		United Kingdom	CF48 4DR

Sponsors and Collaborators

• Chemi S.p.A.

Investigators

• Study Director: Paolo Bettica, MD, Italfarmaco S.p.A.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Chemi S.p.A.
• ClinicalTrials.gov Identifier: NCT02081950
• Other Study ID Numbers: ENOXA/13/1
• First Posted: Mar 7, 2014
• Last Update Posted: Nov 12, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Chemi S.p.A.: enoxaparin sodium
• Additional relevant MeSH terms: Enoxaparin; Enoxaparin sodium

Study Results

Participant Flow

Recruitment Details	No details are specified in the CSR
Pre-assignment Detail	This is a single arm study and not a parallel group study. This means that the participants are 14 in total. The 14 eligible subjects received 1 dose of s.c. Clexane in Treatment Period 1 and 1 dose of S.C. Clexane in Treatment Period 2 (1 dose/period). Each Treatment Period was of 2 days duration.

Arm/Group Title	Clexane 80 mg
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Period Title: Treatment Period 1
STARTED	14
COMPLETED	14
NOT COMPLETED	0
Period Title: Treatment Period 1
STARTED	14
COMPLETED	14
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Clexane - PK Population
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Overall Participants	14
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.4 (8.72)
Sex: Female, Male (Count of Participants)
Female	7 50%
Male	7 50%
Region of Enrollment (participants) [Number]
United Kingdom	14 100%

Outcome Measures

1. Primary Outcome

Title	Anti-FXa Cmax
Description	Enoxaparin exerts its anticoagulant 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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [IU/mL]	0.999 (0.255)	0.926 (0.204)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least square mean ratio
	Estimated Value	93.65
	Confidence Interval	(2-Sided) 90%; 87.56 to 100.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Anti-FXa AUC0-t
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. AUC0-t is the area under the plasma concentration versus time curve from the time of dosing to the time (t) of the last observed value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [h*IU/mL]	9.511 (2.303)	9.479 (1.990)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least square mean ratio
	Estimated Value	100.46
	Confidence Interval	(2-Sided) 90%; 95.74 to 105.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Anti-FXa AUC0-inf
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. AUC0-inf is the AUC extrapolated to infinity from dosing time, based on the last observed value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [h*IU/mL]	9.911 (2.345)	9.949 (2.050)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least square mean ratio
	Estimated Value	101.16
	Confidence Interval	(2-Sided) 90%; 96.32 to 106.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Anti-FIIa Cmax
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [IU/mL]	0.112 (0.027)	0.107 (0.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least square mean ratio
	Estimated Value	94.88
	Confidence Interval	(2-Sided) 90%; 88.49 to 101.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Anti-FIIA AUC0-t
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. AUC0-t is the area under the plasma concentration versus time curve from the time of dosing to the time (t) of the last observed value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [h*IU/mL]	0.692 (0.233)	0.696 (0.264)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least square mean ratio
	Estimated Value	97.13
	Confidence Interval	(2-Sided) 90%; 89.93 to 104.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Anti-FIIA AUC0-inf
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. AUC0-inf is the AUC extrapolated to infinity from dosing time, based on the last observed value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	9
Mean (Standard Deviation) [h*IU/mL]	1.107 (0.517)	1.127 (0.366)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least square mean ratio
	Estimated Value	108.84
	Confidence Interval	(2-Sided) 90%; 95.61 to 123.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Anti-FXa Tmax
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. tmax is the time to Cmax.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [hours]	3.50 (0.76)	4.36 (1.74)

8. Secondary Outcome

Title	Anti-FXa Lambda Zeta
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration versus time curve.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [1/hour]	0.16 (0.06)	0.14 (0.04)

9. Secondary Outcome

Title	Anti-FXa t1/2
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. t1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [hours]	4.87 (1.39)	5.19 (1.47)

10. Secondary Outcome

Title	Anti-FXa Cmin
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Cmin is the minimum plasma activity/concentration.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [IU/mL]	0.000 (0.0000)	0.004 (0.0160)

11. Secondary Outcome

Title	Anti-FXa Tmin
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Tmin is time to Cmin. If the minimum value occurred at >1 time point, tmin was defined as the first time point with this value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [hours]	2.57 (9.621)	0.00 (0.000)

12. Secondary Outcome

Title	Anti-FIIa Tmax
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. tmax is time to Cmax. if the maximum value occurred at >1 time point, tmax was defined as the first time point with this value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [hours]	3.61 (0.74)	4.00 (1.41)

13. Secondary Outcome

Title	Anti-FIIa Lambda Zeta
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration versus time curve.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	9
Mean (Standard Deviation) [1/hour]	0.19 (0.08)	0.17 (0.07)

14. Secondary Outcome

Title	Anti-FIIa t1/2
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. t1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	9
Mean (Standard Deviation) [hours]	4.45 (2.11)	4.86 (2.02)

15. Secondary Outcome

Title	Anti-FIIa Cmin
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. Cmin is the minimum plasma activity/concentration.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [IU/mL]	0.000 (0.000)	0.000 (0.000)

16. Secondary Outcome

Title	Anti-FIIa Tmin
Description	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). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. 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. tmin is the time to minimum concentration.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [hours]	0.00 (0.000)	0.00 (0.000)

17. Secondary Outcome

Title	Thrombin/FIIa Generation AUC0-t
Description	Enoxaparin may have the ability to modulate the fibrinolytic process, by virtue of its ability to inhibit FIIa activity and its generation. Thrombin generation test is an integral indicator of the blood clotting system status. This parameter is used for monitoring enoxaparin therapy in patients. AUC0-t is the area under the plasma concentration versus time curve from the time of dosing to the time (t) of the last observed value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [h*nM]	4034.262 (1955.041)	4050.840 (1662.359)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least square mean ratio
	Estimated Value	102.45
	Confidence Interval	(2-Sided) 90%; 96.31 to 109.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Thrombin/FIIa Generation Cmin
Description	Enoxaparin may have the ability to modulate the fibrinolytic process, by virtue of their ability to inhibit FIIa activity and its generation. Thrombin generation test is an integral indicator of the blood clotting system status. This parameter is used for monitoring enoxaparin therapy in patients. Cmin is the minimum plasma activity/concentration.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [nM]	17.407 (12.562)	16.971 (12.467)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	geometric least square mean ratio
	Estimated Value	95.84
	Confidence Interval	(2-Sided) 90%; 79.11 to 116.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Thrombin/FIIa Generation Tmin
Description	Enoxaparin may have the ability to modulate the fibrinolytic process, by virtue of its ability to inhibit FIIa activity and its generation. Thrombin generation test is an integral indicator of the blood clotting system status. This parameter is used for monitoring enoxaparin therapy in patients. Tmin is time to Cmin. If the minimum value occurred at > 1 time-point Tmin was defined as the first time-point with this value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [hours]	3.500 (0.855)	3.250 (0.803)

20. Secondary Outcome

Title	TFPI Cmax
Description	Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [U/mL]	2.349 (0.464)	2.344 (0.488)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	geometric least square mean ratio
	Estimated Value	99.54
	Confidence Interval	(2-Sided) 90%; 95.69 to 103.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	TFPI Tmax
Description	Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Tmax is the time to Cmax. If the maximum value occurred at > 1 time-point Tmax was defined as the first time-point with this value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [hours]	2.79 (2.04)	2.54 (1.99)

22. Secondary Outcome

Title	TFPI Lambda Zeta
Description	Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant 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 versus time curve. The parameter was calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase (e.g. ≥ 3 non-zero plasma concentrations).
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	6	6
Mean (Standard Deviation) [1/hour]	0.019 (0.003)	0.014 (0.005)

23. Secondary Outcome

Title	TFPI T1/2
Description	Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	6	6
Mean (Standard Deviation) [hours]	37.17 (6.68)	57.49 (28.92)

24. Secondary Outcome

Title	TFPI AUC0-t
Description	Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant 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.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [h*U/mL]	55.208 (12.282)	53.937 (9.857)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	geometric least square mean ratio
	Estimated Value	98.36
	Confidence Interval	(2-Sided) 90%; 95.31 to 101.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	TFPI AUC0-inf
Description	Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant 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. AUC0-inf was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	6	6
Mean (Standard Deviation) [h*U/mL]	123.777 (34.861)	162.976 (54.363)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	geometric least square mean ratio
	Estimated Value	111.3
	Confidence Interval	(2-Sided) 90%; 99.73 to 124.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	TFPI Tmin
Description	Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Tmin is the time of Cmin. If the minimum value occurred at > 1 time-point Tmin was defined as the first time-point with this value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [hours]	18.860 (7.263)	17.430 (5.345)

27. Secondary Outcome

Title	TFPI Cmin
Description	Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Cmin is the minimum plasma activity/concentration.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [IU/mL]	1.253 (0.291)	1.227 (0.273)

28. Secondary Outcome

Title	Anti-FXa/Anti-FIIa Cmax
Description	Anti-FXa/anti-FIIa activity Cmax is reported. Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [U/mL]	9.095 (1.464)	9.020 (1.838)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments	Results were obtained using a mixed-effects ANOVA with fixed effect of study period and a random effect for subject
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	geometric least square mean ratio
	Estimated Value	98.7
	Confidence Interval	(2-Sided) 90%; 93.16 to 104.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Secondary Outcome

Title	Anti-FXa/Anti-FIIa AUC0-t
Description	Anti-FXa/anti-FIIa activity AUC0-t is reported. 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.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [h*nM]	15.137 (5.619)	16.927 (12.466)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	geometric least square mean ratio
	Estimated Value	103.43
	Confidence Interval	(2-Sided) 90%; 94.5 to 113.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Secondary Outcome

Title	Anti-FXa/Anti-FIIa AUC0-inf
Description	Anti-FXa/anti-FIIa activity AUC0-inf is reported. AUC0-inf is the AUC extrapolated to infinity from dosing time, based on the last observed value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	9
Mean (Standard Deviation) [h*U/mL]	10.143 (3.184)	8.941 (2.545)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 1, Treatment Period 2
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	geometric least square mean ratio
	Estimated Value	92.92
	Confidence Interval	(2-Sided) 90%; 80.58 to 107.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

31. Secondary Outcome

Title	Anti-FXa/Anti-FIIa Tmax
Description	Anti-FXa/anti-FIIa activity Tmax is reported. Tmax is the Time to Cmax. If the maximum value occurred at > 1 time-point Tmax was defined as the first time-point with this value.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
Mean (Standard Deviation) [hours]	1.02 (0.33)	1.11 (0.33)

32. Secondary Outcome

Title	Anti-FXa/Anti-FIIa Lambda Zeta
Description	Anti-FXa/anti-FIIa activity lambda zeta is reported. Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase (e.g. ≥ 3 non-zero plasma concentrations).
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	9
Mean (Standard Deviation) [1/hour]	1.09 (0.91)	1.05 (0.58)

33. Secondary Outcome

Title	Anti-FXa/Anti-FIIa t1/2
Description	Anti-FXa/anti-FIIa activity t1/2 is reported. t1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	9
Mean (Standard Deviation) [hours]	1.37 (0.80)	1.30 (0.81)

34. Secondary Outcome

Title	Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs
Description	Description of adverse event profile in healthy volunteers after administration of Enoxaparin sodium s.c. as above described.
Time Frame	Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2.

Outcome Measure Data

Analysis Population Description

Safety Population: All subjects who received at least 1 dose of study medication were included in the safety analysis.

Arm/Group Title	Treatment Period 1	Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
Measure Participants	14	14
TEAEs	4 28.6%	2 NaN
serious TEAEs	0 0%	0 NaN
TEAEs heading to withdrawal	0 0%	0 NaN
Mild TEAEs	3 21.4%	2 NaN
Moderate TEAEs	1 7.1%	0 NaN
TEAEs not related	1 7.1%	1 NaN
TEAEs related	2 14.3%	1 NaN
TEAEs Unkown	1 7.1%	0 NaN

Adverse Events

Time Frame	At Day 0, 1 and 2 during treatment period 1, and Day 0, 1 and 2 during treatment period 2.
Arm/Group Title	Treatment Period 1		Treatment Period 2
Arm/Group Description	Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 1, one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.		Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). Study drug was administered on the morning of Day 1 following an overnight fast. There were at least 7 days between each dose administration. In period 2 one dose of Clexane was administered s.c. into the left or right side of the abdomen (alternating sides with Treatment Period). This dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti FXa activity) in 0.8 mL of water for injection.
All Cause Mortality
	Treatment Period 1		Treatment Period 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Serious Adverse Events
	Treatment Period 1		Treatment Period 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Treatment Period 1		Treatment Period 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/14 (28.6%)		2/14 (14.3%)
Injury, poisoning and procedural complications
Contusion	2/14 (14.3%)	2	1/14 (7.1%)	1
Nervous system disorders
Dizziness	0/14 (0%)	0	1/14 (7.1%)	1
Headache	2/14 (14.3%)	2	0/14 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.