Etude (Study) Phase I Enox - UnFractionated Heparin (UFH)
Study Details
Study Description
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):
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to compare the pharmacokinetic and the pharmacodynamic profile between 3 different timing of administration of the UFH
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to assess the tolerability of the different anticoagulation protocols
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A 70 U/kg of UnFractionated Heparin (UFH) administered intravenously at 4 hours following the last injection of enoxaparin |
Drug: Enoxaparin
|
| Experimental: B 70 U/kg of UnFractionated Heparin (UFH) administered intravenously at 6 hours following the last injection of enoxaparin |
Drug: Enoxaparin
|
| Experimental: C 70 U/kg of UnFractionated Heparin (UFH) administered intravenously at 10 hours following the last injection of enoxaparin |
Drug: Enoxaparin
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
Eligibility Criteria
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)
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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
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Normal vital signs after 10 minutes resting in supine position:
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95 mmHg < systolic blood pressure (SBP) < 140 mmHg;
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45 mmHg < diastolic blood pressure (DBP) < 90 mmHg;
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40 bpm < heart rate < 100 bpm.
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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
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Normal gynecological examination no longer than 12 months before inclusion.
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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
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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
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Subject with detectable antibody against heparin in the blood
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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.
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Subject with diabetes or other cardiovascular or metabolic disease
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Subject with INR > 1.5
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Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month)
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Blood donation or blood loss within one month before administration
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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
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Presence or history of drug allergy, or allergic disease diagnosed and treated by a physician
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History or presence of drug or alcohol abuse (alcohol consumption > 40 grams/day)
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Smoking more than 5 cigarettes or equivalent/day, or unable to stop smoking during the study
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Excessive consumption of beverages with xanthine bases (> 4 cups or glasses/day)
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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:
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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
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Subject who cannot be contacted in case of emergency
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sanofi-Aventis Administrative Office | Paris | France |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Kazuki Otani, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
- ENOXA_C_02537
- 2007-000884-99