Tolerability , PK/PD and Safety of Dabigatran Etexilate Oral Liquid Formulation in Children < 1 Year of Age

Central measurement: The mean activated partial thromboplastin time (aPTT) coagulation time at 2 h and 12 h (±2 h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation.

Time frame: 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean aPTT (activated partial thromboplastin time) ratio at 2 h and 12 h (±2 h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation. aPTT ratio= aPTT (post dose)/aPTT (baseline). The mean of aPTT ratio is presented.

Time frame: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean Ecarin Clotting Time (ECT) ratio at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation. ECT ratio= ECT(Post dose)/ECT(baseline), The mean of ECT ratio is presented.

Time frame: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean of dTT (AntiFactor IIa activity) coagulation time at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation.

Time frame: 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean of dTT (AntiFactor IIa activity) ratio at 2 h and 12 h (±2 h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation. dTT ratio= dTT(post dose)/dTT(baseline). The mean of dTT ratio is presented.

Time frame: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean of Ecarin Clotting Time (ECT) coagulation time at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation.

Time frame: 2 h, and 12 h after dosing on day 1

Population: PKS

Plasma concentrations of total dabigatran, 2h and 12 h (+/-2h) post administration of dabigatran etexilate.

Time frame: 2 hours (h) and 12h after drug administration on day 1

Population: Pharmacokinetic set (PKS): This patient set included all treated patients who provided at least 1 PK/PD observation and had no important Protocol violations (PVs) with respect to statistical analysis of Pharmacokinetic (PK) or Pharmacodynamic (PD ) endpoints.

The investigator was to provide a global clinical assessment of tolerability and acceptability of study medication by the patient.This assessment was based on 5-point scale (good, satisfactory, not satisfactory, bad, not assessable).

Time frame: Day 1 (immediately after dosing)

Population: Treated set

Percentage of patients with all adverse events (AEs) during the treatment period (including REP).

Time frame: Within two days after the administration of trial medication, up to 3 days

Population: Treated set

Percentage of patients with Incidence of all bleeding events(major, clinically relevant non-major (CRNM) & minor) during the treatment period (including the residual effect period).Bleeding events were classified as follow: Major bleeding: 1) Fatal bleeding 2) Clinically overt bleeding associated with decrease in haemoglobin of at least 2 g/dL (20 g/L) in 24-h-period 3) Bleeding that was retroperitoneal, pulmonary, intracranial, or otherwise involved the central nervous system 4) Bleeding that required surgical intervention in an operating suite. CRNM bleeding: 1) Overt bleeding for which a blood product was administered & which was not directly attributable to the patient's underlying medical condition 2) Bleeding that required medical or surgical intervention to restore haemostasis, other than in an operating suite. Minor bleeding defined as any overt or macroscopic evidence of bleeding that did not fulfil the criteria for either major bleeding or CRNM bleeding.

Time frame: Within two days after the administration of trial medication, up to 3 days

Population: Treated set

Linear regression models were used for modeling the relationship between total dabigatran plasma concentration and coagulation parameters APTT values. For our simple regression model, R-squared is equal to the square of Pearson's coefficient of correlation. The R-squared can be between 0 and 1. R-squared =1 means a perfect fit.

Time frame: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Linear regression models were used for modeling the relationship between total dabigatran plasma concentration and coagulation parameters dTT (AntiFactor IIa activity) values. For our simple regression model, R-squared is equal to the square of Pearson's coefficient of correlation. The R-squared can be between 0 and 1. R-squared =1 means a perfect fit.

Time frame: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Linear regression models were used for modeling the relationship between total dabigatran plasma concentration and coagulation parameters ECT values. For our simple regression model, R-squared is equal to the square of Pearson's coefficient of correlation. The R-squared can be between 0 and 1. R-squared =1 means a perfect fit.

Time frame: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS