Primary Objective: \- To assess the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of Semuloparin \[AVE5026\] (assessed from the anti-Xa activity of Semuloparin) in children in order to determine the dose to be assessed in a clinical efficacy/safety study in this population. Secondary Objective: \- To assess the tolerability of Semuloparin when administered at a weight-adjusted, once daily dose for up to 30 days in patients less than 18 years of age with central venous line.
The maximum study duration for a participant was 68 days broken down as follows: * Screening period: up to 6 days, * Treatment period: minimum 6 days and maximum 30 days, * Follow-up period with an end of study visit performed 4 weeks (30 +/-2 days) post treatment. Enrollment staggered by age group starting with the older children (≥12 years). In each younger age group, enrolment was planned to initiate only following a review by the Data Monitoring Committee (DMC) of the clinical safety data and available PK and PD data from the first 3 out of 7 children from the previous older age group. Enrollment of infants \<3 months was planned to initiate after recruitment of all patients ≥3 months had been completed and all data analyzed by the DMC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
2
Solution for injection in single dose vials (10 mg/mL and 20 mg/mL) Subcutaneous injection
Investigational Site Number 348001
Budapest, Hungary
Pharmacokinetics: Plasma concentrations of Semuloparin
A validated anti-Xa chromogenic enzyme assay, with addition of AT-III in excess was to be used to assess plasma concentrations of semuloparin. A full population PK model of semuloparin in children (including covariates assessment) was to be established and individual pharmacokinetic parameters were be estimated.
Time frame: 6 samples; 0.5-1h and 6h after D4 injection, 1.5-4h and 12h after D5 injection, just before and 8h after D6 injection
Pharmacodynamic activity (anti-Xa activity) of Semuloparin
A validated anti-Xa chromogenic enzyme assay, without addition of AT-III in excess, was to be used to assess pharmacodynamic activity (factor Xa inhibition) of semuloparin. A full population PK/PD model of semuloparin in children (including covariates assessment) was to be established and individual pharmacodynamic parameters were to be estimated.
Time frame: 6 samples; 0.5-1h and 6h after D4 injection, 1.5-4h and 12h after D5 injection, just before and 8h after D6 injection
Safety parameters including bleeding
Time frame: up to 30+/- 2 days post treatment
Safety parameters including transfusions requirement
Time frame: up to 30+/- 2 days post treatment
Safety parameters including hemoglobin, platelet count
Time frame: up to 30+/- 2 days post treatment
Safety parameters including liver and renal laboratory data
Time frame: up to 30+/- 2 days post treatment
Safety parameters including serious adverse events
Time frame: up to 30+/- 2 days post treatment
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Safety parameters including non-serious adverse events
Time frame: up to 30+/- 2 days post treatment