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

NCT02232802 | Completed Phase 1 Results

• 1 other identifier: ENOXA/14/2
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief 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.
• 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.

Conditions

Enoxaparin Sodium is Administered to Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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)

  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)

  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)

  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)

  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)

  At day 1(0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16h) and Day 2 (24 and 36h)

Study Arms (2)

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.

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.

Drug: Enoxaparin Sodium

Interventions

Enoxaparin Sodium DRUG

comparison of bioavailability of generic Enoxaparin Sodium and Clexane

Also known as: Clexane

Enoxaparin Sodium Chemi

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.
• 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.

You may not qualify if:

• 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.

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: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2014
• First Posted: September 5, 2014
• Study Start: August 4, 2014
• Primary Completion: December 5, 2014
• Study Completion: December 5, 2014
• Last Updated: October 20, 2020
• Results First Posted: October 20, 2020

Record last verified: 2020-10

Locations

GB (1)