Etude (Study) Phase I Enox - UnFractionated Heparin (UFH)

NCT00622115 | Completed Phase 1

• 2 other identifiers: ENOXA_C_025372007-000884-99
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective:

• to characterize the pharmacokinetic and the pharmacodynamic profile after intravenous bolus injection of unfractionated heparin (UFH) after repeated sc 100 IU anti-Xa/kg (corresponding to 1 mg/kg) twice a day during 2.5 days (every 12±2hrs) administrations of enoxaparin in Caucasian healthy subjects. Secondary objective(s):
• to compare the pharmacokinetic and the pharmacodynamic profile between 3 different timing of administration of the UFH
• to assess the tolerability of the different anticoagulation protocols

Conditions

Thrombosis

Outcome Measures

Primary Outcomes (1)

• Concentration-time profiles of anti-Xa and anti-IIa levels

  At baseline (Day 2) after the morning enoxaparin injection and at day 3 from pre-dose of enoxaparin and lasting until 14 hours after the enoxaparin injection.

Secondary Outcomes (3)

• Effect-time profiles of ACT, TGTppp and TGTprp

  At baseline (Day 2) after the morning enoxaparin sc injection and at day 3 from pre-dose of enoxaparin and lasting until 14 hours after the enoxaparin injection.

• PFA100 levels measured

  At pre-dose, 4h and 14h post dose of enoxaparin

• Documentation of adverse event, physical examination, clinical laboratory safety, vital signs and ECG recording at prespecified time-points.

  during the entire study

Study Arms (3)

A

EXPERIMENTAL

70 U/kg of UnFractionated Heparin (UFH) administered intravenously at 4 hours following the last injection of enoxaparin

Drug: Enoxaparin

B

EXPERIMENTAL

70 U/kg of UnFractionated Heparin (UFH) administered intravenously at 6 hours following the last injection of enoxaparin

Drug: Enoxaparin

C

EXPERIMENTAL

70 U/kg of UnFractionated Heparin (UFH) administered intravenously at 10 hours following the last injection of enoxaparin

Drug: Enoxaparin

Interventions

Enoxaparin DRUG

A; B; C

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Caucasian
• Male and female subjects, between 40 and 60 years of age
• Body weight between 50 kg and 90 kg if male and between 40 and 80 kg if female with Body Mass Index (BMI) between 18 and 29 kg/m2
• Health Status:
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination)
• Subject with hypertension, hypo- or hyperthyroidism or dyslipidemia will be included if their concomitant pathology is well-controlled by treatment for at least one year
• Normal vital signs after 10 minutes resting in supine position:
• mmHg \< systolic blood pressure (SBP) \< 140 mmHg;
• mmHg \< diastolic blood pressure (DBP) \< 90 mmHg;
• bpm \< heart rate \< 100 bpm.
• Normal 12-lead electrocardiogram (ECG); 120 ms \< PR \< 220 ms, QRS \< 120 ms, QTc ≤ 430 ms for male, 450 ms for female or not considered as clinically significant by the investigator
• Laboratory parameters within the normal range unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects; hepatic enzymes (aspartate amino-transferase or AST, alanine amino-transferase or ALT) should be strictly below the upper laboratory norm.
• Platelets ≥ 150 000 / mm3
• Mean corpuscular volume (MCV) and gamma glutamyl-transferase (GGT) should be strictly in the normal range of the laboratory
• Activated partial thromboplastin time (aPTT) ratio should be comprised between 0.95 and 1.15

You may not qualify if:

• Medical history and clinical status:
• Contra-indication to anticoagulant therapy
• Subject with known increased bleeding time, hemophilia, thrombocytopenia, and/or history of any vascular purpura
• Subject with detectable antibody against heparin in the blood
• Any history or presence of clinically relevant cardiovascular, gynecologic (for women), pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurologic, psychiatric, systemic, ocular or infectious disease that is capable of altering the absorption, metabolism, or elimination of drugs, or of constituting a risk factor when taking the study medication; any acute infectious disease or signs of acute illness; except subject with hypertension, hypo- or hyperthyroidism or dyslipidemia if well-controlled by treatment for at least one year.
• Subject with diabetes or other cardiovascular or metabolic disease
• Subject with INR \> 1.5
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month)
• Blood donation or blood loss within one month before administration
• Symptomatic hypotension whatever the decrease in blood pressure or asymptomatic postural hypotension defined by a decrease in SBP equal to or greater than 20 mmHg within three minutes when changing from the supine to the standing position
• Presence or history of drug allergy, or allergic disease diagnosed and treated by a physician
• History or presence of drug or alcohol abuse (alcohol consumption \> 40 grams/day)
• Smoking more than 5 cigarettes or equivalent/day, or unable to stop smoking during the study
• Excessive consumption of beverages with xanthine bases (\> 4 cups or glasses/day)
• Pregnancy (defined as positive beta-HCG plasma test that can not be explicated by menopauses), breast-feeding for female, any history or presence of clinically relevant gynecologic disease

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Sanofi-Aventis Administrative Office

Paris, France

Location

Related Publications (1)

• Drouet L, Bal dit Sollier C, Martin J. Adding intravenous unfractionated heparin to standard enoxaparin causes excessive anticoagulation not detected by activated clotting time: results of the STACK-on to ENOXaparin (STACKENOX) study. Am Heart J. 2009 Aug;158(2):177-84. doi: 10.1016/j.ahj.2009.05.022.

  PMID: 19619692 BACKGROUND

MeSH Terms

Conditions

Thrombosis

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Kazuki Otani

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 13, 2008
• First Posted: February 22, 2008
• Study Start: July 1, 2007
• Primary Completion: November 1, 2007
• Study Completion: November 1, 2007
• Last Updated: March 15, 2011

Record last verified: 2011-03

Locations

FR (1)