Thrombosis
Conditions
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
Interventions
DRUGEnoxaparin
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
France
Outcome results
None listed