Safety and Tolerability of Dabigatran Etexilate Solution in Children 1 to < 12 Years of Age

AUC0-tz (area under the concentration time curve of the free dabigatran in plasma over the time interval 0 up to the last quantifiable data point). Endpoint can only be calculated for single dose patients. For multiple dose patients the time points do not allow calculation of AUC0-tz (no profile, only one measurement after selected doses, refer to primary outcome no. 1 and 2).

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate

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

AUC0-tz (area under the concentration time curve of the total dabigatran in plasma over the time interval 0 up to the last quantifiable data point). Endpoint can only be calculated for single dose patients. For multiple dose patients the time points do not allow calculation of AUC0-tz (no profile, only one measurement after selected doses, refer to primary outcome no. 1 and 2).

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate

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

Central measurement of aPTT (activated partial thromboplastin time) at predose and 2 and 10 h after intake of study medication. For multiple dose patients only local measurements were planned. The Standard Deviation presented below is actually the % coefficient of variation.

Time frame: at predose and 2 and 10 h after intake of study medication.

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

Central measurement of dTT (diluted thrombin time) at predose and 2 and 10 h after intake of study medication. The Standard Deviation presented below are actually the % coefficient of variation

Time frame: at predose and 2 and 10 h after intake of study medication.

Population: PKS (evaluable cases)

Central measurement of ECT (ecarin clotting time) at predose and 2 and 10 h after intake of study medication. ECT was not planned to be measured in the multiple dose group. The Standard Deviation presented below are actually the % coefficient of variation

Time frame: at predose and 2 and 10 h after intake of study medication.

Population: PKS (evaluable cases)

Cmax (maximum measured concentration of free dabigatran in plasma). Endpoint can only be calculated for single dose patients. For multiple dose patients the time points do not allow calculation of Cmax (no profile, only one measurement after selected doses, refer to primary outcome no. 1 and 2).

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate

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

Cmax (maximum measured concentration of total dabigatran in plasma). Endpoint can only be calculated for single dose patients. For multiple dose patients the time points do not allow calculation of Cmax (no profile, only one measurement after selected doses, refer to primary outcome no. 1 and 2).

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate

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

Major: Fatal bleeding, Clinically overt bleeding associated with decrease in haemoglobin of at least 2 g/dL in 24-h-period,bleeding that was retroperitoneal,pulmonary,intracranial,or otherwise involved the central nervous system,bleeding that required surgical intervention in an operating suite. CRNM: Overt bleeding for which a blood product was administered & which was not directly attributable to the patient's underlying medical condition,bleeding that required medical or surgical intervention to restore haemostasis,other than in an operating suite. Minor: Any overt or macroscopic evidence of bleeding that did not fulfil the criteria for either major bleeding or CRNM bleeding. For multiple dosing,all events with an onset date after the date of first dose until the end of trial treatment including 3 days after the last treatment and for single dosing,all events with an onset during the 48-h-period after study medication intake were assigned to the on-treatment period.

Time frame: Up to 6 days

Population: Treated set

Plasma concentration of free dabigatran (BIBR 953 ZW)

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate and at 2 h, 50 h, and 72 h after multiple dose administration of dabigatran etexilate

Population: PKS (evaluable cases)

Plasma concentration of metabolite BIBR 1087 SE

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate and at 2 h, 50 h, and 72 h after multiple dose administration of dabigatran etexilate

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

Plasma concentration of metabolite BIBR 951 BS

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate and at 2 h, 50 h, and 72 h after multiple dose administration of dabigatran etexilate

Population: PKS (evaluable cases)

Plasma concentration of total dabigatran (SUM BIBR 953 ZW)

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate and at 2 h, 50 h, and 72 h after multiple dose administration of dabigatran etexilate

Population: Pharmacokinetic set (PKS): This patient set included all treated patients who provided at least one pharmacokinetic/ pharmacodynamic (PK/PD) observation and had no important protocol violations (PVs) with respect to the statistical analysis of PK or PD endpoints.~PKS (evaluable cases)

Plasma concentration of unchanged dabigatran etexilate (BIBR 1048 BS). Some values are NA because Values were below the limit of quantification. Not calculated as reliable estimation can only be performed when at least 2/3 of the data are available and thus the Geometric Mean (gMean) and Geometric Coefficient of Variation (gCV) is not calculated according to internal rules.

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate and at 2 h, 50 h, and 72 h after multiple dose administration of dabigatran etexilate

Population: PKS (evaluable cases)

tmax (time from dosing to maximum measured concentration of free dabigatran in plasma). Endpoint can only be calculated for single dose patients. For multiple dose patients the time points do not allow calculation of tmax (no profile, only one measurement after selected doses, refer to primary outcome no. 1 and 2).

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate

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

tmax (time from dosing to maximum measured concentration of total dabigatran in plasma). Endpoint can only be calculated for single dose patients. For multiple dose patients the time points do not allow calculation of tmax (no profile, only one measurement after selected doses, refer to primary outcome no. 1 and 2).

Time frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate

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

The investigator was to provide a global clinical assessment of tolerability 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

The investigator was to provide a global clinical assessment of tolerability including patient taste assessment.This assessment was based on 6-point scale (Very good, good, satisfactory, bad, very bad, missing). The taste assessment was only provided when the patient was old enough to evaluate the taste.

Time frame: Day 1 (immediately after dosing)

Population: Treated set

Percentage of patients with any adverse events during the treatment period. For patients with multiple dosing, all AEs with an onset date after the date of first dose until the end of trial treatment including 3 days after the last treatment were assigned to the on-treatment period. For patients with single dosing, all AEs with an onset during the 48-h-period after study medication intake were assigned to the on-treatment period.

Time frame: Up to 6 days

Population: Treated set

Percentage of patients with changes in laboratory and clinical parameters such as liver enzymes and physical examination. Clinically Relevant Abnormalities for Laboratory Parameters were reported.

Time frame: During the treatment period, Up to 6 days

Population: Treated set