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

NCT02081950 | Completed Phase 1 Results

• 1 other identifier: ENOXA/13/1
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Clexane is Administered to Healthy Volunteers

Keywords

enoxaparin sodium

Outcome Measures

Primary Outcomes (6)

• Anti-FXa Cmax

  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.

  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 AUC0-t

  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.

  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 AUC0-inf

  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.

  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-FIIa Cmax

  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.

  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-FIIA AUC0-t

  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.

  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-FIIA AUC0-inf

  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.

  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.

Secondary Outcomes (28)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (1)

Enoxaparin sodium

EXPERIMENTAL

Enoxaparin sodium (80mg) is administered subcutaneously as a single dose, in 2 periods.

Biological: Enoxaparin sodium

Interventions

Enoxaparin sodium BIOLOGICAL

comparison of 2 different administration of drug

Also known as: Clexane

Enoxaparin sodium

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chemi S.p.A.: lead

Study Sites (1)

Simbec Research Ltd

Merthyr Tydfil, CF48 4DR, United Kingdom

Location

MeSH Terms

Interventions

enoxaparin sodium; Enoxaparin

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Paolo Bettica, MD
• Organization: Chemi SpA (Part of Italfarmaco Group)

p.bettica@italfarmaco.com

+39 02 64431

Study Officials

• Paolo Bettica, MD

  Italfarmaco S.p.A.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: March 7, 2014
• Study Start: March 1, 2014
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: November 12, 2020
• Results First Posted: September 29, 2020

Record last verified: 2020-10

Locations

GB (1)