Trial Outcomes & Findings for A Single-Dose Trial to Examine the Within Subject Variability of Clexane® in Healthy Adults Under Fasting Conditions (NCT NCT02081950)
NCT ID: NCT02081950
Last Updated: 2020-11-12
Results Overview
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.
COMPLETED
PHASE1
14 participants
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.
2020-11-12
Participant Flow
No details are specified in the CSR
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.
Participant milestones
| Measure |
Clexane 80 mg
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.
|
|---|---|
|
Treatment Period 1
STARTED
|
14
|
|
Treatment Period 1
COMPLETED
|
14
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
|
Treatment Period 2
STARTED
|
14
|
|
Treatment Period 2
COMPLETED
|
14
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Single-Dose Trial to Examine the Within Subject Variability of Clexane® in Healthy Adults Under Fasting Conditions
Baseline characteristics by cohort
| Measure |
Clexane - PK Population
n=14 Participants
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.
|
|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
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0 Participants
n=5 Participants
|
|
Age, Continuous
|
31.4 years
STANDARD_DEVIATION 8.72 • n=5 Participants
|
|
Sex: Female, Male
Female
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7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
14 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
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|---|---|---|
|
Anti-FXa Cmax
|
0.999 IU/mL
Standard Deviation 0.255
|
0.926 IU/mL
Standard Deviation 0.204
|
PRIMARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
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|---|---|---|
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Anti-FXa AUC0-t
|
9.511 h*IU/mL
Standard Deviation 2.303
|
9.479 h*IU/mL
Standard Deviation 1.990
|
PRIMARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
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|---|---|---|
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Anti-FXa AUC0-inf
|
9.911 h*IU/mL
Standard Deviation 2.345
|
9.949 h*IU/mL
Standard Deviation 2.050
|
PRIMARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FIIa Cmax
|
0.112 IU/mL
Standard Deviation 0.027
|
0.107 IU/mL
Standard Deviation 0.029
|
PRIMARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FIIA AUC0-t
|
0.692 h*IU/mL
Standard Deviation 0.233
|
0.696 h*IU/mL
Standard Deviation 0.264
|
PRIMARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=9 Participants
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.
|
|---|---|---|
|
Anti-FIIA AUC0-inf
|
1.107 h*IU/mL
Standard Deviation 0.517
|
1.127 h*IU/mL
Standard Deviation 0.366
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FXa Tmax
|
3.50 hours
Standard Deviation 0.76
|
4.36 hours
Standard Deviation 1.74
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FXa Lambda Zeta
|
0.16 1/hour
Standard Deviation 0.06
|
0.14 1/hour
Standard Deviation 0.04
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FXa t1/2
|
4.87 hours
Standard Deviation 1.39
|
5.19 hours
Standard Deviation 1.47
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FXa Cmin
|
0.000 IU/mL
Standard Deviation 0.0000
|
0.004 IU/mL
Standard Deviation 0.0160
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FXa Tmin
|
2.57 hours
Standard Deviation 9.621
|
0.00 hours
Standard Deviation 0.000
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FIIa Tmax
|
3.61 hours
Standard Deviation 0.74
|
4.00 hours
Standard Deviation 1.41
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=9 Participants
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.
|
|---|---|---|
|
Anti-FIIa Lambda Zeta
|
0.19 1/hour
Standard Deviation 0.08
|
0.17 1/hour
Standard Deviation 0.07
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=9 Participants
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.
|
|---|---|---|
|
Anti-FIIa t1/2
|
4.45 hours
Standard Deviation 2.11
|
4.86 hours
Standard Deviation 2.02
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FIIa Cmin
|
0.000 IU/mL
Standard Deviation 0.000
|
0.000 IU/mL
Standard Deviation 0.000
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FIIa Tmin
|
0.00 hours
Standard Deviation 0.000
|
0.00 hours
Standard Deviation 0.000
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Thrombin/FIIa Generation AUC0-t
|
4034.262 h*nM
Standard Deviation 1955.041
|
4050.840 h*nM
Standard Deviation 1662.359
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Thrombin/FIIa Generation Cmin
|
17.407 nM
Standard Deviation 12.562
|
16.971 nM
Standard Deviation 12.467
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Thrombin/FIIa Generation Tmin
|
3.500 hours
Standard Deviation 0.855
|
3.250 hours
Standard Deviation 0.803
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
TFPI Cmax
|
2.349 U/mL
Standard Deviation 0.464
|
2.344 U/mL
Standard Deviation 0.488
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
TFPI Tmax
|
2.79 hours
Standard Deviation 2.04
|
2.54 hours
Standard Deviation 1.99
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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).
Outcome measures
| Measure |
Treatment Period 1
n=6 Participants
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.
|
Treatment Period 2
n=6 Participants
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.
|
|---|---|---|
|
TFPI Lambda Zeta
|
0.019 1/hour
Standard Deviation 0.003
|
0.014 1/hour
Standard Deviation 0.005
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=6 Participants
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.
|
Treatment Period 2
n=6 Participants
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.
|
|---|---|---|
|
TFPI T1/2
|
37.17 hours
Standard Deviation 6.68
|
57.49 hours
Standard Deviation 28.92
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
TFPI AUC0-t
|
55.208 h*U/mL
Standard Deviation 12.282
|
53.937 h*U/mL
Standard Deviation 9.857
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=6 Participants
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.
|
Treatment Period 2
n=6 Participants
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.
|
|---|---|---|
|
TFPI AUC0-inf
|
123.777 h*U/mL
Standard Deviation 34.861
|
162.976 h*U/mL
Standard Deviation 54.363
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
TFPI Tmin
|
18.860 hours
Standard Deviation 7.263
|
17.430 hours
Standard Deviation 5.345
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
TFPI Cmin
|
1.253 IU/mL
Standard Deviation 0.291
|
1.227 IU/mL
Standard Deviation 0.273
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FXa/Anti-FIIa Cmax
|
9.095 U/mL
Standard Deviation 1.464
|
9.020 U/mL
Standard Deviation 1.838
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FXa/Anti-FIIa AUC0-t
|
15.137 h*nM
Standard Deviation 5.619
|
16.927 h*nM
Standard Deviation 12.466
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=9 Participants
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.
|
|---|---|---|
|
Anti-FXa/Anti-FIIa AUC0-inf
|
10.143 h*U/mL
Standard Deviation 3.184
|
8.941 h*U/mL
Standard Deviation 2.545
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Anti-FXa/Anti-FIIa Tmax
|
1.02 hours
Standard Deviation 0.33
|
1.11 hours
Standard Deviation 0.33
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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).
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=9 Participants
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.
|
|---|---|---|
|
Anti-FXa/Anti-FIIa Lambda Zeta
|
1.09 1/hour
Standard Deviation 0.91
|
1.05 1/hour
Standard Deviation 0.58
|
SECONDARY outcome
Timeframe: 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.Population: PK Population: All subjects who received study medication in both Treatment Periods, had sufficient plasma activity/concentration-time profiles and who did not violate the protocol in such a way that may have invalidated or biased the results (major protocol violators) were included in the PK analysis.
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.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=9 Participants
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.
|
|---|---|---|
|
Anti-FXa/Anti-FIIa t1/2
|
1.37 hours
Standard Deviation 0.80
|
1.30 hours
Standard Deviation 0.81
|
SECONDARY outcome
Timeframe: 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.Population: Safety Population: All subjects who received at least 1 dose of study medication were included in the safety analysis.
Description of adverse event profile in healthy volunteers after administration of Enoxaparin sodium s.c. as above described.
Outcome measures
| Measure |
Treatment Period 1
n=14 Participants
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.
|
Treatment Period 2
n=14 Participants
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.
|
|---|---|---|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs
Moderate TEAEs
|
1 participants
|
0 participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs
TEAEs not related
|
1 participants
|
1 participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs
TEAEs
|
4 participants
|
2 participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs
serious TEAEs
|
0 participants
|
0 participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs
TEAEs heading to withdrawal
|
0 participants
|
0 participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs
Mild TEAEs
|
3 participants
|
2 participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs
TEAEs related
|
2 participants
|
1 participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs
TEAEs Unkown
|
1 participants
|
0 participants
|
Adverse Events
Treatment Period 1
Treatment Period 2
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment Period 1
n=14 participants at risk
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.
|
Treatment Period 2
n=14 participants at risk
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.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Contusion
|
14.3%
2/14 • Number of events 2 • At Day 0, 1 and 2 during treatment period 1, and Day 0, 1 and 2 during treatment period 2.
|
7.1%
1/14 • Number of events 1 • At Day 0, 1 and 2 during treatment period 1, and Day 0, 1 and 2 during treatment period 2.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/14 • At Day 0, 1 and 2 during treatment period 1, and Day 0, 1 and 2 during treatment period 2.
|
7.1%
1/14 • Number of events 1 • At Day 0, 1 and 2 during treatment period 1, and Day 0, 1 and 2 during treatment period 2.
|
|
Nervous system disorders
Headache
|
14.3%
2/14 • Number of events 2 • At Day 0, 1 and 2 during treatment period 1, and Day 0, 1 and 2 during treatment period 2.
|
0.00%
0/14 • At Day 0, 1 and 2 during treatment period 1, and Day 0, 1 and 2 during treatment period 2.
|
Additional Information
Paolo Bettica, MD
Chemi SpA (Part of Italfarmaco Group)
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place