Trial Outcomes & Findings for Bioavailability Study of Enoxaparin Sodium Chemi and Clexane s.c. (NCT NCT02232802)
NCT ID: NCT02232802
Last Updated: 2020-10-20
Results Overview
Cmax is the maximum measured plasma activity/concentration. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
COMPLETED
PHASE1
47 participants
At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
2020-10-20
Participant Flow
Forty-seven (47) subjects (23 male and 24 female) were enrolled in the study. The subjects were selected from a large panel who offered their services as healthy volunteers for the purpose of undertaking REC and Regulatory Authority-approved studies on drug safety, absorption and disposition.
The study comprised a screening visit and 2 treatment periods. Only two doses were scheduled to be administered: first dose (period 1) - wash out (at least 7 days) - 2nd dose (period 2) - wash out period (at least 7 days). Each treatment period was of 2 days duration. Screening assessments: from Day -14 to Day -1.
Participant milestones
| Measure |
Test IMP - Reference IMP
These patients reveiced the following sequence:
Test IMP: A single-dose of 80mg/0.8 mL Chemi Enoxaparin. Reference IMP: A single-dose of 80mg/0.8 mL Clexane® Each dose was administered s.c. into the left or right side of the abdomen (alternating sides with treatment period).
Each dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection.
Subjects remained in an upright position whilst receiving each dose and for 4 h afterwards.
There were at least 7 days between each dose administration for males and female subjects of nonchildbearing potential. Female subjects of child bearing potential underwent a washout period of approximately 28 days.
|
Reference IMP - Test IMP
These patients reveiced the following sequence:
Reference IMP: A single-dose of 80mg/0.8 mL Clexane® Test IMP: A single-dose of 80mg/0.8 mL Chemi Enoxaparin. Each dose was administered s.c. into the left or right side of the abdomen (alternating sides with treatment period).
Each dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection.
Subjects remained in an upright position whilst receiving each dose and for 4 h afterwards.
There were at least 7 days between each dose administration for males and female subjects of nonchildbearing potential.
Female subjects of child bearing potential underwent a washout period of approximately 28 days.
|
|---|---|---|
|
Period 1
STARTED
|
24
|
23
|
|
Period 1
COMPLETED
|
22
|
22
|
|
Period 1
NOT COMPLETED
|
2
|
1
|
|
Washout
STARTED
|
22
|
22
|
|
Washout
COMPLETED
|
22
|
22
|
|
Washout
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
22
|
22
|
|
Period 2
COMPLETED
|
22
|
22
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Test IMP - Reference IMP
These patients reveiced the following sequence:
Test IMP: A single-dose of 80mg/0.8 mL Chemi Enoxaparin. Reference IMP: A single-dose of 80mg/0.8 mL Clexane® Each dose was administered s.c. into the left or right side of the abdomen (alternating sides with treatment period).
Each dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection.
Subjects remained in an upright position whilst receiving each dose and for 4 h afterwards.
There were at least 7 days between each dose administration for males and female subjects of nonchildbearing potential. Female subjects of child bearing potential underwent a washout period of approximately 28 days.
|
Reference IMP - Test IMP
These patients reveiced the following sequence:
Reference IMP: A single-dose of 80mg/0.8 mL Clexane® Test IMP: A single-dose of 80mg/0.8 mL Chemi Enoxaparin. Each dose was administered s.c. into the left or right side of the abdomen (alternating sides with treatment period).
Each dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection.
Subjects remained in an upright position whilst receiving each dose and for 4 h afterwards.
There were at least 7 days between each dose administration for males and female subjects of nonchildbearing potential.
Female subjects of child bearing potential underwent a washout period of approximately 28 days.
|
|---|---|---|
|
Period 1
Sponsor request
|
1
|
0
|
|
Period 1
Adverse Event
|
1
|
1
|
Baseline Characteristics
Bioavailability Study of Enoxaparin Sodium Chemi and Clexane s.c.
Baseline characteristics by cohort
| Measure |
Test IMP - Reference IMP
n=24 Participants
These patients reveiced the following sequence:
Test IMP: A single-dose of 80mg/0.8 mL Chemi Enoxaparin. Reference IMP: A single-dose of 80mg/0.8 mL Clexane® Each dose was administered s.c. into the left or right side of the abdomen (alternating sides with treatment period).
Each dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection.
Subjects remained in an upright position whilst receiving each dose and for 4 h afterwards.
There were at least 7 days between each dose administration for males and female subjects of nonchildbearing potential. Female subjects of child bearing potential underwent a washout period of approximately 28 days.
|
Reference IMP - Test IMP
n=23 Participants
These patients reveiced the following sequence:
Reference IMP: A single-dose of 80mg/0.8 mL Clexane® Test IMP: A single-dose of 80mg/0.8 mL Chemi Enoxaparin. Each dose was administered s.c. into the left or right side of the abdomen (alternating sides with treatment period).
Each dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection.
Subjects remained in an upright position whilst receiving each dose and for 4 h afterwards.
There were at least 7 days between each dose administration for males and female subjects of nonchildbearing potential.
Female subjects of child bearing potential underwent a washout period of approximately 28 days.
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=93 Participants
|
23 Participants
n=4 Participants
|
47 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
|
Region of Enrollment
United Kingdom
|
24 participants
n=93 Participants
|
23 participants
n=4 Participants
|
47 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
Cmax is the maximum measured plasma activity/concentration. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Cmax (Anti-FXa and Anti-FIIa)
Anti-FXa
|
0.8593 IU/mL
Standard Deviation 0.18056
|
0.8698 IU/mL
Standard Deviation 0.20921
|
|
Cmax (Anti-FXa and Anti-FIIa)
Anti-thrombin/factor IIa
|
0.1187 IU/mL
Standard Deviation 0.03451
|
0.1296 IU/mL
Standard Deviation 0.03713
|
PRIMARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII). thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
AUC0-t (Anti-FXa and Anti-FIIa)
Anti-FXa
|
9.6259 h*IU/mL
Standard Deviation 1.68590
|
9.3927 h*IU/mL
Standard Deviation 1.83943
|
|
AUC0-t (Anti-FXa and Anti-FIIa)
Anti-FIIa
|
1.0234 h*IU/mL
Standard Deviation 0.28817
|
1.1097 h*IU/mL
Standard Deviation 0.31668
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=43 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
AUC0-inf (Anti-FXa and Anti-FIIa)
Anti-FXa
|
10.2789 h*IU/mL
Standard Deviation 1.71377
|
9.9197 h*IU/mL
Standard Deviation 1.86143
|
|
AUC0-inf (Anti-FXa and Anti-FIIa)
Anti-FIIa
|
1.1489 h*IU/mL
Standard Deviation 0.29243
|
1.2926 h*IU/mL
Standard Deviation 0.40401
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
Tmax is the time to Cmax. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity. Results are presented as derived plasma PK parameters.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Tmax (Anti-FXa and Anti-FIIa)
Anti-FXa
|
4.0000 Hours
Interval 2.0 to 6.0
|
4.0000 Hours
Interval 3.0 to 6.0
|
|
Tmax (Anti-FXa and Anti-FIIa)
Anti-FIIa
|
4.0000 Hours
Interval 2.0 to 6.0
|
4.0000 Hours
Interval 3.0 to 16.0
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=43 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Lambda Zeta (Anti-FXa and Anti-FIIa)
Anti-FXa
|
0.0962 1/hour
Standard Deviation 0.04251
|
0.1133 1/hour
Standard Deviation 0.04337
|
|
Lambda Zeta (Anti-FXa and Anti-FIIa)
Anti-IIa
|
0.2111 1/hour
Standard Deviation 0.10435
|
0.1938 1/hour
Standard Deviation 0.11612
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=43 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
t1/2 (Anti-FXa and Anti-FIIa)
Anti-FXa
|
8.4757 hours
Standard Deviation 3.22737
|
6.9507 hours
Standard Deviation 2.42567
|
|
t1/2 (Anti-FXa and Anti-FIIa)
Anti-FIIa
|
4.6214 hours
Standard Deviation 2.97971
|
6.5045 hours
Standard Deviation 8.67539
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
Tmin is the time of Cmin. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Tmin (Anti-FXa and Anti-FIIa)
Anti-FXa
|
0.00 hours
Standard Deviation 0.000
|
0.00 hours
Standard Deviation 0.000
|
|
Tmin (Anti-FXa and Anti-FIIa)
Anti-FIIa
|
4.18 hours
Standard Deviation 8.538
|
6.91 hours
Standard Deviation 12.211
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity. Blood samples (2 x 10 mL) for determination of plasma anti-FIIa and anti-FXa were collected from a forearm vein into a Citrate Sarstedt Monovette at the following time-points (at day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)) and kept frozen until analysis. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity. Results are presented as derived plasma PK parameters.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=43 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
AUC%ex (Anti-FXa and Anti-FIIa)
Anti-FXa
|
6.4515 percentage of total value of AUC
Standard Deviation 2.68130
|
4.9683 percentage of total value of AUC
Standard Deviation 1.80897
|
|
AUC%ex (Anti-FXa and Anti-FIIa)
Anti-FIIa
|
12.0593 percentage of total value of AUC
Standard Deviation 7.68842
|
12.0906 percentage of total value of AUC
Standard Deviation 9.02925
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
Cmin is the minimum plasma activity/concentration. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti- FIIa) activity. Results are presented as derived plasma PK parameters.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Cmin (Anti-FXa and Anti-FIIa)
Anti-FXa
|
0.000 IU/mL
Standard Deviation 0.0000
|
0.000 IU/mL
Standard Deviation 0.0000
|
|
Cmin (Anti-FXa and Anti-FIIa)
Anti-FIIa
|
0.002 IU/mL
Standard Deviation 0.0044
|
0.002 IU/mL
Standard Deviation 0.0042
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
Cmax is the maximum measured plasma activity/concentration. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Cmax (Tissue Factor Pathway Inhibitor, TFPI)
|
2.4327 IU/mL
Standard Deviation 0.35998
|
2.3391 IU/mL
Standard Deviation 0.33903
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)Cmax is the maximum measured plasma activity/concentration. The ratio of anti-FXa/anti-FIIa activity was calculated for each parameter. Reults are presented as derived ratio of PK parameters.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Cmax (Anti-FXa/Anti-FIIa Ratio)
|
7.4450 ratio
Standard Deviation 1.04983
|
6.8546 ratio
Standard Deviation 0.95651
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method. Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
AUC0-t (Derived Thrombin Generation)
|
3731.0710 h*nM
Standard Deviation 1375.97298
|
3597.3375 h*nM
Standard Deviation 1104.52084
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample. Cmin is the minimum plasma activity/concentration.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Cmin (Derived Thrombin Generation)
|
13.534 nM
Standard Deviation 7.6300
|
11.543 nM
Standard Deviation 6.9299
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample. Tmin is the time of Cmin.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Tmin (Derived Thrombin Generation)
|
3.67 hours
Standard Deviation 1.136
|
3.64 hours
Standard Deviation 0.911
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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 anti-coagulant activity, by inhibiting FXa generation and free FXa. AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
AUC0-t (Tissue Factor Pathway Inhibitor, TFPI)
|
56.1828 h*Unit/mL
Standard Deviation 7.91060
|
55.7851 h*Unit/mL
Standard Deviation 8.43154
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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 anti-coagulant activity, by inhibiting FXa generation and free FXa. AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=23 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=18 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
AUC0-inf (Tissue Factor Pathway Inhibitor, TFPI)
|
140.8383 h*Unit/mL
Standard Deviation 36.06655
|
173.9833 h*Unit/mL
Standard Deviation 123.89404
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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 anti-coagulant activity, by inhibiting FXa generation and free FXa. Tmax is the time to Cmax
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Tmax (Tissue Factor Pathway Inhibitor, TFPI)
|
1.7500 hours
Standard Deviation 0.83178
|
1.8068 hours
Standard Deviation 1.20665
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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 anti-coagulant activity, by inhibiting FXa generation and free FXa. Cmin is the minimum plasma activity/concentration.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Cmin (Tissue Factor Pathway Inhibitor, TFPI)
|
1.261 Unit/mL
Standard Deviation 0.2277
|
1.290 Unit/mL
Standard Deviation 0.2288
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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 anti-coagulant activity, by inhibiting FXa generation and free FXa. Tmin is the time of Cmin.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Tmin (Tissue Factor Pathway Inhibitor, TFPI)
|
16.27 hours
Standard Deviation 5.275
|
15.55 hours
Standard Deviation 6.293
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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 anti-coagulant activity, by inhibiting FXa generation and free FXa. T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=23 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=18 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
T1/2 (Tissue Factor Pathway Inhibitor, TFPI)
|
41.6397 hours
Standard Deviation 8.66880
|
57.2439 hours
Standard Deviation 46.13993
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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)\[5\], which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa. Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=23 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=18 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Lambda Zeta (Tissue Factor Pathway Inhibitor, TFPI)
|
0.0172 1/hour
Standard Deviation 0.00323
|
0.0148 1/hour
Standard Deviation 0.00440
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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 release tissue factor pathway inhibitor (TFPI)\[5\], which is thought to contribute to anti-coagulant activity, by inhibiting FXa generation and free FXa. AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=23 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=18 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
AUC%ex (Tissue Factor Pathway Inhibitor, TFPI)
|
58.9149 percentage of total AUC
Standard Deviation 5.07416
|
63.0497 percentage of total AUC
Standard Deviation 8.81000
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter. AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
AUC0-t (Anti-FXa/Anti-FIIa Ratio)
|
9.7836 h*IU/mL
Standard Deviation 1.75225
|
8.7967 h*IU/mL
Standard Deviation 1.64043
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter. AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. It was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=36 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=38 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
AUC0-inf (Anti-FXa/Anti-FIIa Ratio)
|
9.1620 h*IU/mL
Standard Deviation 1.47121
|
8.2160 h*IU/mL
Standard Deviation 1.60673
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter. T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=36 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=38 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
T1/2 (Anti-FXa/Anti-FIIa Ratio)
|
2.6595 hours
Standard Deviation 2.06574
|
1.9420 hours
Standard Deviation 1.47865
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter. Cmin is the minimun plasma activity/concentration.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=7 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=7 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Cmin (Anti-FXa/Anti-FIIa Ratio)
|
0.000 UI/mL
Standard Deviation 0.000
|
0.000 UI/mL
Standard Deviation 0.000
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter. Tmin is the time of Cmin.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=9 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=12 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Tmin (Anti-FXa/Anti-FIIa Ratio)
|
0.00 hours
Standard Deviation 0.000
|
0.00 hours
Standard Deviation 0.000
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter. AUC%ex is the residual area, i.e. the percentage of the area under the curve (AUC) extrapolated to infinity observed from Tlast to infinity.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=36 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=38 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
AUC%ex (Anti-FXa/Anti-FIIa Ratio)
|
0.8078 percentage of total AUC
Standard Deviation 0.71131
|
0.6385 percentage of total AUC
Standard Deviation 0.52118
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter. Tmax is the time to Cmax.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=44 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=44 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Tmax (Anti-FXa/Anti-FIIa Ratio)
|
0.9973 hours
Standard Deviation 0.28432
|
0.9830 hours
Standard Deviation 0.24467
|
SECONDARY outcome
Timeframe: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)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.
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter. Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration vs time curve.
Outcome measures
| Measure |
Enoxaparin Sodium Chemi (Test IMP)
n=36 Participants
Enoxaparin Sodium Chemi (i.e. Test IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
Clexane (Reference IMP)
n=38 Participants
Clexane (i.e. Reference IMP) was administered to healthy subjects. A single dose contained 80 mg enoxaparin sodium (equivalent to 8,000 international units (IU) anti-factor Xa (anti-FXa activity) in 0.8 mL water for injection. It was administered s.c . into the right or left side of the abdomen (alternating sides with treatment period).
|
|---|---|---|
|
Lambda Zeta (Anti-FXa/Anti-FIIa Ratio)
|
0.6699 1/hour
Standard Deviation 0.52191
|
1.0937 1/hour
Standard Deviation 1.82862
|
Adverse Events
Enoxaparin Sodium Chemi
Clexane
Serious adverse events
| Measure |
Enoxaparin Sodium Chemi
n=46 participants at risk
Enoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.
Enoxaparin Sodium: comparison of bioavailability of generic Enoxaparin Sodium and Clexane
|
Clexane
n=45 participants at risk
Enoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.
Enoxaparin Sodium: comparison of bioavailability of generic Enoxaparin Sodium and Clexane
|
|---|---|---|
|
Congenital, familial and genetic disorders
Fibrous dysplasia
|
0.00%
0/46 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
2.2%
1/45 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
|
Infections and infestations
Cellulitis
|
2.2%
1/46 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
0.00%
0/45 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
Other adverse events
| Measure |
Enoxaparin Sodium Chemi
n=46 participants at risk
Enoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.
Enoxaparin Sodium: comparison of bioavailability of generic Enoxaparin Sodium and Clexane
|
Clexane
n=45 participants at risk
Enoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.
Enoxaparin Sodium: comparison of bioavailability of generic Enoxaparin Sodium and Clexane
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
2.2%
1/46 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
2.2%
1/45 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
|
Nervous system disorders
Headache
|
4.3%
2/46 • Number of events 2 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
2.2%
1/45 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
|
Nervous system disorders
Syncope
|
2.2%
1/46 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
2.2%
1/45 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.2%
1/46 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
0.00%
0/45 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/46 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
2.2%
1/45 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
2.2%
1/46 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
0.00%
0/45 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.2%
1/46 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
0.00%
0/45 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
|
Musculoskeletal and connective tissue disorders
Ligament sprain
|
0.00%
0/46 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
2.2%
1/45 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/46 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
2.2%
1/45 • Number of events 1 • Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.
|
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