Enoxaparin Sodium is Administered to Healthy VolunteersPhase 1NCT02232802

Bioavailability Study of Enoxaparin Sodium Chemi and Clexane s.c.

A Phase 1 study testing Enoxaparin Sodium in people with Enoxaparin Sodium is Administered to Healthy Volunteers, run by Chemi S.p.A. at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary objective of the trial is to assess the single-dose relative bioavailability of Chemi Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by subcutaneous (s.c.) injection, under fasting conditions in healthy volunteers. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Enoxaparin Sodium is Administered to Healthy Volunteers
What is being tested?: Enoxaparin Sodium
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 47 participants
Where: 1 siteUnited Kingdom
Study dates: 4 Aug 2014to 5 Dec 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy male or female volunteer between 18 and 55 years of age.
Subject with a BMI of 18-30 (Body Mass Index = Body weight (kg) / [Height (m)]2)
Subject with no clinically significant abnormal serum biochemistry, haematology, coagulation factors and urine examination values within 14 days of the first dose.
Subject with no clinically significant abnormalities in 12-lead electrocardiogram (ECG) and vital signs determined within 14 days of the first dose.
Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (HbsAg) and hepatitis C virus antibody (HCV) results.

Who cannot join

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. Or with history or presence of alcoholism or drug abuse;
Subject with clinically relevant abnormal physical findings or clinically relevant abnormal laboratory values indicative of physical illness;
Female subject who is pregnant or lactating
Female subject with weight < 45 kg or male subject with weight < 57 kg.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Simbec Research Ltd
Merthyr Tydfil, CF48 4DR

Other trials in United Kingdom

About this study

Official title: Comparative, Randomized, Single-dose, 2-way Cross Over Bioavailability Study of Enoxaparin Sodium Chemi (80 mg/0.8mL) and Clexane® (80 mg/0.8mL) s.c. in Healthy Adult Subjects Under Fasting Conditions.

The primary objective of the trial is to assess the single-dose relative bioavailability of Chemi Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by subcutaneous (s.c.) injection, under fasting conditions in healthy volunteers.
The secondary objective of the trial is to assess safety and tolerability of Chemi Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by s.c. injection, under fasting conditions in healthy volunteers.

Read the detailed description

This is an open-label, randomised, single-dose, 2-way crossover study to determine the comparative bioavailability of enoxaparin sodium from the Chemi Enoxaparin s.c. (80 mg/0.8mL) with that from the reference IMP, Clexane® s.c. (80 mg/0.8mL), following single dose administration in healthy male and female subjects.

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

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

The post study visit will be conducted on Day 2 (36 h post-dose) of Treatment Period 2.

Conditions: Enoxaparin Sodium is Administered to Healthy Volunteers
Being tested: Enoxaparin Sodium

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Enoxaparin SodiumDrug
Also called Clexane
comparison of bioavailability of generic Enoxaparin Sodium and Clexane
Enoxaparin SodiumDrug
Also called generic Enoxaparin Sodium
comparison of bioavailability of generic Enoxaparin Sodium and Clexane

Study groups in NCT02232802
Study group	Role	What they receive
Enoxaparin Sodium Chemi	Experimental	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. Receives: Drug: Enoxaparin Sodium
Clexane	Experimental	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. Receives: Drug: Enoxaparin Sodium

What is being measured

The primary outcome is the main question the study is designed to answer.

Cmax (Anti-FXa and Anti-FIIa)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-t (Anti-FXa and Anti-FIIa)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)

Secondary outcomes (28)

AUC0-inf (Anti-FXa and Anti-FIIa)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmax (Anti-FXa and Anti-FIIa)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Lambda Zeta (Anti-FXa and Anti-FIIa)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
t1/2 (Anti-FXa and Anti-FIIa)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmin (Anti-FXa and Anti-FIIa)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC%ex (Anti-FXa and Anti-FIIa)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmin (Anti-FXa and Anti-FIIa)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmax (Tissue Factor Pathway Inhibitor, TFPI)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmax (Anti-FXa/Anti-FIIa Ratio)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-t (Derived Thrombin Generation)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmin (Derived Thrombin Generation)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmin (Derived Thrombin Generation)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-t (Tissue Factor Pathway Inhibitor, TFPI)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-inf (Tissue Factor Pathway Inhibitor, TFPI)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmax (Tissue Factor Pathway Inhibitor, TFPI)
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
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmin (Tissue Factor Pathway Inhibitor, TFPI)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmin (Tissue Factor Pathway Inhibitor, TFPI)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
T1/2 (Tissue Factor Pathway Inhibitor, TFPI)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Lambda Zeta (Tissue Factor Pathway Inhibitor, TFPI)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC%ex (Tissue Factor Pathway Inhibitor, TFPI)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-t (Anti-FXa/Anti-FIIa Ratio)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-inf (Anti-FXa/Anti-FIIa Ratio)
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
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
T1/2 (Anti-FXa/Anti-FIIa Ratio)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmin (Anti-FXa/Anti-FIIa Ratio)
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
Cmin is the minimun plasma activity/concentration.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmin (Anti-FXa/Anti-FIIa Ratio)
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
Tmin is the time of Cmin.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC%ex (Anti-FXa/Anti-FIIa Ratio)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmax (Anti-FXa/Anti-FIIa Ratio)
The ratio of anti-FXa/anti-FIIa activity was calculated for each major parameter.
Tmax is the time to Cmax.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Lambda Zeta (Anti-FXa/Anti-FIIa Ratio)
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.
Measured: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Aug 20145 Dec 2014

First posted5 Sep 2014 (estimated)
Study start4 Aug 2014
Primary completion5 Dec 2014
Study completion5 Dec 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Enoxaparin Sodium is Administered to Healthy VolunteersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02232802
Sponsor's protocol ID: ENOXA/14/2
Status last verified: Oct 2020
First submitted: 3 Sep 2014
Last updated: 20 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 20 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Comparative, Randomized, Single-dose, 2-way Cross Over Bioavailability Study of Enoxaparin Sodium Chemi (80 mg/0.8mL) and Clexane® (80 mg/0.8mL) s.c. in Healthy Adult Subjects Under Fasting Conditions.
ClinicalTrials.gov ID: NCT02232802
Acronym / sponsor ID: ENOXA/14/2
Conditions: Enoxaparin Sodium is Administered to Healthy Volunteers
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 47 participants (actual)
Lead sponsor: Chemi S.p.A.Industry (pharma, biotech, devices)
Study start: 4 Aug 2014 (actual)
Primary completion: 5 Dec 2014 (actual)
Study completion: 5 Dec 2014 (actual)
First posted: 5 Sep 2014 (estimated)
Results: Posted 20 Oct 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The primary objective of the trial is to assess the single-dose relative bioavailability of Chemi Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by subcutaneous (s.c.) injection, under fasting conditions in healthy volunteers.
The secondary objective of the trial is to assess safety and tolerability of Chemi Enoxaparin (80 mg/0.8 mL) and Clexane® (80 mg/0.8 mL) administered by s.c. injection, under fasting conditions in healthy volunteers.

Detailed description

The post study visit will be conducted on Day 2 (36 h post-dose) of Treatment Period 2.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Enoxaparin Sodium Chemi	Experimental	Drug: Enoxaparin SodiumEnoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.
Clexane	Experimental	Drug: Enoxaparin SodiumEnoxaparin Sodium Chemi and Clexane will be administered to healthy subjects. Each subject will receive each treatment over two separate treatment periods under fasting conditions.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Healthy male or female volunteer between 18 and 55 years of age.
Subject with a BMI of 18-30 (Body Mass Index = Body weight (kg) / [Height (m)]2)
Subject with no clinically significant abnormal serum biochemistry, haematology, coagulation factors and urine examination values within 14 days of the first dose.
Subject with no clinically significant abnormalities in 12-lead electrocardiogram (ECG) and vital signs determined within 14 days of the first dose.
Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (HbsAg) and hepatitis C virus antibody (HCV) results.

Key exclusion criteria (5 listed)

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. Or with history or presence of alcoholism or drug abuse;
Subject with clinically relevant abnormal physical findings or clinically relevant abnormal laboratory values indicative of physical illness;
Female subject who is pregnant or lactating
Female subject with weight < 45 kg or male subject with weight < 57 kg.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Enoxaparin SodiumAlso: Clexanecomparison of bioavailability of generic Enoxaparin Sodium and Clexane	Drug	Enoxaparin Sodium Chemi
Enoxaparin SodiumAlso: generic Enoxaparin Sodiumcomparison of bioavailability of generic Enoxaparin Sodium and Clexane	Drug	Clexane

Primary outcome

Cmax (Anti-FXa and Anti-FIIa)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
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.
AUC0-t (Anti-FXa and Anti-FIIa)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
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.

28 secondary outcomes

AUC0-inf (Anti-FXa and Anti-FIIa)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmax (Anti-FXa and Anti-FIIa)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Lambda Zeta (Anti-FXa and Anti-FIIa)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
t1/2 (Anti-FXa and Anti-FIIa)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmin (Anti-FXa and Anti-FIIa)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC%ex (Anti-FXa and Anti-FIIa)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmin (Anti-FXa and Anti-FIIa)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmax (Tissue Factor Pathway Inhibitor, TFPI)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmax (Anti-FXa/Anti-FIIa Ratio)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-t (Derived Thrombin Generation)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmin (Derived Thrombin Generation)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmin (Derived Thrombin Generation)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-t (Tissue Factor Pathway Inhibitor, TFPI)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-inf (Tissue Factor Pathway Inhibitor, TFPI)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmax (Tissue Factor Pathway Inhibitor, TFPI)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmin (Tissue Factor Pathway Inhibitor, TFPI)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmin (Tissue Factor Pathway Inhibitor, TFPI)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
T1/2 (Tissue Factor Pathway Inhibitor, TFPI)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Lambda Zeta (Tissue Factor Pathway Inhibitor, TFPI)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC%ex (Tissue Factor Pathway Inhibitor, TFPI)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-t (Anti-FXa/Anti-FIIa Ratio)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC0-inf (Anti-FXa/Anti-FIIa Ratio)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
T1/2 (Anti-FXa/Anti-FIIa Ratio)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Cmin (Anti-FXa/Anti-FIIa Ratio)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmin (Anti-FXa/Anti-FIIa Ratio)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
AUC%ex (Anti-FXa/Anti-FIIa Ratio)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Tmax (Anti-FXa/Anti-FIIa Ratio)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)
Lambda Zeta (Anti-FXa/Anti-FIIa Ratio)
Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)

Results and safety

Results posted to the registry on 20 Oct 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Test IMP - Reference IMP	24	22
Reference IMP - Test IMP	23	22

Primary outcome: Cmax (Anti-FXa and Anti-FIIa)

Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h). Mean (Standard Deviation). Unit: IU/mL

Measure	Enoxaparin Sodium Chemi (Test IMP) n = 44	Clexane (Reference IMP) n = 44
Anti-FXa	0.8593 (0.18056)	0.8698 (0.20921)
Anti-thrombin/factor IIa	0.1187 (0.03451)	0.1296 (0.03713)

Enoxaparin Sodium Chemi (Test IMP) vs Clexane (Reference IMP): least square mean difference ratio: 99.42 (95% CI 96.28 to 102.65)
Enoxaparin Sodium Chemi (Test IMP) vs Clexane (Reference IMP): least square mean difference ratio: 91.55 (95% CI 86.65 to 96.73)

Population analysed: 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.

Primary outcome: AUC0-t (Anti-FXa and Anti-FIIa)

Time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h). Mean (Standard Deviation). Unit: h*IU/mL

Measure	Enoxaparin Sodium Chemi (Test IMP) n = 44	Clexane (Reference IMP) n = 44
Anti-FXa	9.6259 (1.68590)	9.3927 (1.83943)
Anti-FIIa	1.0234 (0.28817)	1.1097 (0.31668)

Enoxaparin Sodium Chemi (Test IMP) vs Clexane (Reference IMP): least square mean difference ratio: 102.89 (95% CI 100.67 to 105.15)
Enoxaparin Sodium Chemi (Test IMP) vs Clexane (Reference IMP): least square mean difference ratio: 92.37 (95% CI 87.72 to 97.25)

28 secondary outcomes are reported in the full results.

Adverse events

Time frame: Throughout the study: day 1 (pre-dose,0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h), Day 2 (24 and 36h), and post-study follow-up. Follow-up assessments were classified as 'End of study assessments'. They were performed on Day 2, 36 h post-dose, prior to discharging the subject.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Enoxaparin Sodium Chemi	1 of 46 (2.2%)	7 of 46 (15.2%)	0 of 46
Clexane	1 of 45 (2.2%)	5 of 45 (11.1%)	0 of 45

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Paolo Bettica, MD study director

Italfarmaco S.p.A.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Enoxaparin Sodium in people with Enoxaparin Sodium is Administered to Healthy Volunteers, run by Chemi S.p.A. at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cmax (Anti-FXa and Anti-FIIa) (time frame: At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02232802.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2020.