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

NCT ID: NCT00622115

Last Updated: 2011-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2007-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

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

Group Type: EXPERIMENTAL

Enoxaparin

Intervention Type: DRUG

B

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

Group Type: EXPERIMENTAL

Enoxaparin

Intervention Type: DRUG

C

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

Group Type: EXPERIMENTAL

Enoxaparin

Intervention Type: DRUG

Interventions

Enoxaparin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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:

• 95 mmHg < systolic blood pressure (SBP) < 140 mmHg;
• 45 mmHg < diastolic blood pressure (DBP) < 90 mmHg;
• 40 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
• Estimated Creatinine clearance by Cockroft formula should be higher than 50 mL/min
• Non smoker or smoking the equivalent or less than 5 cigarettes a day and able not to smoke during the study hospitalization
• Normal gynecological examination no longer than 12 months before inclusion.
• For female with childbearing potential using an effective contraception method (e.g. intra-uterine device, hormonal contraception, diaphragm and condom) except if postmenopausal for more than 12 months or sterilized for more than three months
• Subject with coagulation test and blood count (including platelets) within the physiological ranges)

Regulations:

• Having given written informed consent prior to any procedure related to the study
• Covered by Health Insurance System and/or in compliance with the recommendations of National Law in force relating to biomedical research
• Not under any administrative or legal supervision

Exclusion Criteria

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

Interfering substance:

• Any medication (including St John's Wort) within 14 days before administration, or within 5 times the elimination half-life of that drug, except for hormonal contraception or replacement therapy, and allowed therapy for stable pathology
• Anti-inflammatory treatments and anti-aggregant treatments are strictly forbidden during the whole study period

General conditions:

• Subject who, in the judgment of the Investigator, is likely to be non-compliant during the study, or unable to cooperate because of a language problem or poor mental development
• Subject in exclusion period of a previous study according to applicable regulations
• Subject who cannot be contacted in case of emergency
• Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff thereof, directly involved in the conduct of the protocol or any other protocol of the Investigating Center
• Subject is an employee of the Investigating Center

Biological status:

• Positive reaction to any of the following tests: HBs antigen, anti-HCV antibodies, anti-HIV1 antibodies, anti-HIV2 antibodies, anti-LMWH antibodies
• Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids)
• Positive alcohol breath or plasma test

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

sanofi-aventis

Principal Investigators

Kazuki Otani

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Administrative Office

Paris, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 19619692 (View on PubMed)

Other Identifiers

2007-000884-99

Identifier Type: -

Identifier Source: secondary_id

ENOXA_C_02537

Identifier Type: -

Identifier Source: org_study_id