A Single-Dose Trial to Examine the Within Subject Variability of Clexane® in Healthy Adults Under Fasting Conditions
- Conditions
- Clexane is Administered to Healthy Volunteers
- Interventions
- Biological: Enoxaparin sodium
- Registration Number
- NCT02081950
- Lead Sponsor
- Chemi S.p.A.
- Brief Summary
Primary: To examine the within subject variability of Clexane (80 mg) in healthy male and female volunteers administered subcutaneously (s.c.) as a single dose, in two periods, under fasting conditions.
Secondary: To monitor safety during the Treatment Periods.
- Detailed Description
This was a pilot, open-label study to evaluate the PK of enoxaparin following s.c. administrations of 80 mg Clexane, on 2 different occasions, in 14 healthy adult subjects.
The study comprised a Screening Visit and 2 Treatment Periods (1 and 2). Screening (Day -14 to Day -1): Screening assessments were carried out within 14 days before administration of the first dose of Clexane. Eligible subjects were asked to return for Treatment Period 1.
Treatment Periods 1 and 2 (Day 0 to Day 26): Eligible subjects received two doses of s.c. Clexane over 2 Treatment Periods (1 dose/period). Final confirmation of eligibility was made prior to dosing during Treatment Period 1. Confirmation of ongoing eligibility was made prior to dosing during Treatment Period 2.
Each Treatment Period was of 2 days duration, from the afternoon before dosing (Day 0) until 36 hours (h) post-dose (evening of Day 2). During each Treatment Period, subjects resided at the Clinical Unit. Study drug was administered on the morning of Day 1 following an overnight fast. Pharmacokinetic (PK) samples were collected pre-dose and up to 36 h post-dose (x14 samples) for the measurement of enoxaparin. Safety was also evaluated at specified times throughout the study. There were at least 7 days between each dose administration. The Post-Study Follow-Up was conducted on Day 2 of Treatment Period 2 after completion of the 36 h PK blood sampling and vital sign check.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 14
- Healthy male or female volunteer between 18 and 55 years of age.
- Female subject of child bearing potential with a negative pregnancy test at the Screening Visit and willing to use 2 effective methods of contraception from Day 1 until 3 months afterwards.
- Subject with no clinically significant abnormal serum biochemistry, haematology, coagulation factors and urine examination values within 14 days of the first dose.
- Female subject with weight < 45 kg or male subject with weight < 57 kg.
- Subject with clinically relevant abnormal physical findings which could interfere with the objective of the study.
- Subject with clinically relevant abnormal laboratory values indicative of physical illness; Hemoglobin <13 g/dL; Absolute platelet count below 100 x 109/L.
- Subject with hypersensitivity or idiosyncratic reaction to enoxaparin and/or low molecular weight heparins, and/or pork products.
- Subject with a relevant history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease. In addition, history or presence of: alcoholism or drug abuse within the past year; clotting disorders; gastric or duodenal ulcers; hypertension; retinopathy; deep venous thrombosis; pulmonary embolism; GI bleeding.
- Subject with any clinically significant illness within 4 weeks prior to dosing.
- Subject with recent use of NSAID and/or aspirin (within 4 weeks of first dose) or the use of any pharmacological agents known to significantly induce or inhibit drug-metabolizing enzymes within 30 days of the first dose. No subject may take any antibiotic agent known to interfere with intestinal microflora within 30 days of the first dose. Subjects with any medical condition requiring regular treatment with prescription drugs.
- Subject with recent severe trauma, surgery (eye surgery), and/or lumbar puncture;
- Female subject who was pregnant or lactating.
- Subject who was a vegetarian.
- Subject who, through completion of the study, would have donated in excess of 500 mL of blood and/or plasma within the previous 3 months.
- Subject who regularly consumed excessive amounts of alcohol.
- Subject who consumed excessive amount of caffeine (> 5 cups of coffee or equivalent per day).
- Subject who was a smoker (cigarettes and tobacco-related products), or ex-smoker who had smoked in the 3 months preceding the study. Subjects were tested for urinary cotinine at screening.
- Subjects who could not tolerate venepuncture.
- Inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function).
- Participation in a New Chemical Entity clinical study within the previous 4 months or a marketed drug clinical study within the previous 3 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Enoxaparin sodium Enoxaparin sodium Enoxaparin sodium (80mg) is administered subcutaneously as a single dose, in 2 periods.
- Primary Outcome Measures
Name Time Method Anti-FXa AUC0-inf Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
AUC0-inf is the AUC extrapolated to infinity from dosing time, based on the last observed value.Anti-FXa AUC0-t Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
AUC0-t is the area under the plasma concentration versus time curve from the time of dosing to the time (t) of the last observed value.Anti-FIIA AUC0-inf Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
AUC0-inf is the AUC extrapolated to infinity from dosing time, based on the last observed value.Anti-FXa Cmax Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anticoagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.Anti-FIIa Cmax Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.Anti-FIIA AUC0-t Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
AUC0-t is the area under the plasma concentration versus time curve from the time of dosing to the time (t) of the last observed value.
- Secondary Outcome Measures
Name Time Method Anti-FXa t1/2 Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
t1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.Anti-FXa Lambda Zeta Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration versus time curve.TFPI Cmax Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.
Anti-FIIa Tmax Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
tmax is time to Cmax. if the maximum value occurred at \>1 time point, tmax was defined as the first time point with this value.Thrombin/FIIa Generation Cmin Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin may have the ability to modulate the fibrinolytic process, by virtue of their ability to inhibit FIIa activity and its generation.
Thrombin generation test is an integral indicator of the blood clotting system status. This parameter is used for monitoring enoxaparin therapy in patients.
Cmin is the minimum plasma activity/concentration.Anti-FXa/Anti-FIIa Tmax Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Anti-FXa/anti-FIIa activity Tmax is reported. Tmax is the Time to Cmax. If the maximum value occurred at \> 1 time-point Tmax was defined as the first time-point with this value.
Anti-FXa Cmin Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
Cmin is the minimum plasma activity/concentration.Thrombin/FIIa Generation Tmin Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin may have the ability to modulate the fibrinolytic process, by virtue of its ability to inhibit FIIa activity and its generation.
Thrombin generation test is an integral indicator of the blood clotting system status. This parameter is used for monitoring enoxaparin therapy in patients.
Tmin is time to Cmin. If the minimum value occurred at \> 1 time-point Tmin was defined as the first time-point with this value.TFPI Cmin Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Cmin is the minimum plasma activity/concentration.
Anti-FXa/Anti-FIIa AUC0-inf Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Anti-FXa/anti-FIIa activity AUC0-inf is reported. AUC0-inf is the AUC extrapolated to infinity from dosing time, based on the last observed value.
Anti-FXa Tmin Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
Tmin is time to Cmin. If the minimum value occurred at \>1 time point, tmin was defined as the first time point with this value.Anti-FIIa t1/2 Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
t1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.Anti-FIIa Cmin Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
Cmin is the minimum plasma activity/concentration.Anti-FIIa Tmin Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
tmin is the time to minimum concentration.Anti-FXa Tmax Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
tmax is the time to Cmax.Thrombin/FIIa Generation AUC0-t Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin may have the ability to modulate the fibrinolytic process, by virtue of its ability to inhibit FIIa activity and its generation.
Thrombin generation test is an integral indicator of the blood clotting system status. This parameter is used for monitoring enoxaparin therapy in patients.
AUC0-t is the area under the plasma concentration versus time curve from the time of dosing to the time (t) of the last observed value.TFPI T1/2 Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa.
T1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.Anti-FIIa Lambda Zeta Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin exerts its anti-coagulant effect primarily via interaction with anti-thrombin III (ATIII), thereby enhancing the inhibitory effect of ATIII on activated factor Xa (FXa) and thrombin/factor IIa (FIIa). Inhibition of FXa activity prevents conversion of prothrombin/factor II (FII) to FIIa and inhibition of FIIa activity (direct/indirect) prevents conversion of fibrinogen to fibrin and therefore clot formation. As enoxaparin cannot be measured directly in blood, the PK of enoxaparin have been studied on the basis of its effect on clotting mechanisms, particularly the inhibition of FXa (anti-FXa) and FIIa (anti-FIIa) activity.
Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration versus time curve.TFPI AUC0-inf Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. AUC0-inf is the area under the activity/concentration-time curve from time 0 extrapolated to infinity. AUC0-inf was calculated as the sum of AUC0-t plus the ratio of the last measurable value to the elimination rate constant.
TFPI Tmin Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Tmin is the time of Cmin. If the minimum value occurred at \> 1 time-point Tmin was defined as the first time-point with this value.
TFPI Tmax Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Tmax is the time to Cmax. If the maximum value occurred at \> 1 time-point Tmax was defined as the first time-point with this value.
TFPI Lambda Zeta Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase (e.g. ≥ 3 non-zero plasma concentrations).
TFPI AUC0-t Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Enoxaparin also releases tissue factor pathway inhibitor (TFPI), which is thought to contribute to anticoagulant activity, by inhibiting FXa generation and free FXa. AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.
Anti-FXa/Anti-FIIa Cmax Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Anti-FXa/anti-FIIa activity Cmax is reported. Cmax is the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and before the administration of a second dose.
Anti-FXa/Anti-FIIa t1/2 Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Anti-FXa/anti-FIIa activity t1/2 is reported. t1/2 is the apparent first-order terminal elimination half-life calculated as 0.693/kel.
Anti-FXa/Anti-FIIa AUC0-t Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Anti-FXa/anti-FIIa activity AUC0-t is reported. AUC0-t is the area under the plasma activity/concentration-time curve from the time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.
Number of Patients With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Severity of TEAEs Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Description of adverse event profile in healthy volunteers after administration of Enoxaparin sodium s.c. as above described.
Anti-FXa/Anti-FIIa Lambda Zeta Pre-dose, and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 and 36 h in Period 1 and Period 2. Anti-FXa/anti-FIIa activity lambda zeta is reported. Lambda zeta is the apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma activity/concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase (e.g. ≥ 3 non-zero plasma concentrations).
Trial Locations
- Locations (1)
Simbec Research Ltd
🇬🇧Merthyr Tydfil, United Kingdom