Etude (Study) Phase I Enox - UnFractionated Heparin (UFH)
Status and phase
Conditions
Treatments
Details and patient eligibility
About
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
Enrollment
Sex
Ages
Volunteers
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:
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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:
- 95 mmHg < systolic blood pressure (SBP) < 140 mmHg;
- 45 mmHg < diastolic blood pressure (DBP) < 90 mmHg;
- 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
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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.
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Platelets ≥ 150 000 / mm3
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Mean corpuscular volume (MCV) and gamma glutamyl-transferase (GGT) should be strictly in the normal range of the laboratory
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Activated partial thromboplastin time (aPTT) ratio should be comprised between 0.95 and 1.15
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Estimated Creatinine clearance by Cockroft formula should be higher than 50 mL/min
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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
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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
Trial design
Primary purpose
Allocation
Interventional model
Masking
72 participants in 3 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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