A Phase I, Pharmacokinetic and Tolerability Study of Intravenous Unfractionated Heparin After Subcutaneous Enoxaparin 1mg/kg Bid Repeated Administration in Healthy Subjects

Sanofi1 site in 1 country72 target enrollmentJuly 2007

ConditionsThrombosis

InterventionsEnoxaparin

DrugsEnoxaparin

Overview

Phase: Phase 1
Intervention: Enoxaparin
Conditions: Thrombosis
Sponsor: Sanofi
Enrollment: 72
Locations: 1
Primary Endpoint: Concentration-time profiles of anti-Xa and anti-IIa levels
Status: Completed
Last Updated: 15 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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

Registry

clinicaltrials.gov

Start Date

July 2007

End Date

November 2007

Last Updated

15 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Sanofi

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.

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

Arms & Interventions

A

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

Intervention: Enoxaparin

B

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

Intervention: Enoxaparin

C

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

Intervention: Enoxaparin

Outcomes

Primary Outcomes

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

Time Frame: 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

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)