Safety and Tolerability of Dabigatran Etexilate in Adolescents

Study Overview
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Brief Summary
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To investigate the safety and tolerability of dabigatran etexilate capsules in a small group of eight adolescent patients.

Official Title
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Open-label Safety and Tolerability Study of Dabigatran Etexilate Mesilate Given for 3 Days at the End of Standard Anticoagulant Therapy in Children Aged 12 Years to Less Than 18 Years

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: dabigatran etexilate


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: males or females 12 to less than 18 years of age objective diagnosis of primary VTE completion of planned treatment course with LMWH or OAC for primary VTE written informed consent by parent (legal guardian) and patient assent Exclusion criteria: weight less than 32 kg conditions associated with increased risk of bleeding severe renal dysfunction or requirement for dialysis active infective endocarditis hepatic disease pregnant females or females not using medically accepted contraceptive method anemia or thrombocytopenia use of prohibited or restricted drug within previous week received investigational drug within past 30 days unreliable patients or patients who have any condition that would not allow safe participation in study

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dabigatran etexilate<br>open label; patient to receive dabigatran etexilate BID for three days | Drug: dabigatran etexilate<br>* 2.14 mg/kg BID to a max 150 mg BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Bleeding Events (Major and Minor) | Patients were carefully assessed for signs and symptoms of bleeding. Bleeding was to be classified as major or minor. Major bleeding had to satisfy one or more of the following criteria: Overt bleeding associated with a decrease in haemoglobin of at least 2 g/dL in 24 hours, Overt bleeding requiring a transfusion of red blood cells, Overt bleeding which was retroperitoneal, intracranial, intraocular, or intraarticular, any overt bleeding deemed by the attending physician to require discontinuation of study medication. Minor bleeds were clinical bleeds that did not fulfill the criteria for major bleeds. | From Screening until 30 days after first drug administration (end of trial visit) | 
| Number of Patients With Adverse Events | Patients with treatment drug related adverse events (DRAEs) and serious adverse events (SAEs) are reported separately for on-treatment and post-treatment period. Events were considered on-treatment if occurring within 72 hours after last drug administration. | From Screening until 30 days after first drug administration (end of trial visit) | 
| Plasma Concentration of Free Dabigatran | Plasma concentration of free dabigatran measured at 72 hours after first dose | 3 days | 
| Plasma Concentration of Total Dabigatran | Plasma concentration of total dabigatran measured at 72 hours after first dose | Day 3 | 
| Thrombin Time (TT) Centrally Measured | Measurement of TT was performed locally and centrally by Hemoclot Thrombin Inhibitor clotting assay. | Day 3 | 
| TT Locally Measured | Measurement of TT was performed locally and centrally by Hemoclot Thrombin Inhibitor clotting assay. | Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activated Partial Thromboplastin Time (aPTT) Centrally Measured | Measurement of aPTT was performed locally and centrally using validated assays. | Day 3 | 
| aPTT Locally Measured | Measurement of aPTT was performed locally and centrally using validated assays. | Day 3 | 
| Ecarin Clotting Time (ECT) | Measurement of ECT was performed locally and centrally using validated assays. Descriptive statistics is only performed for the centrally measured ECT. | Day 3 | 
| Patients With Clinically Relevant Changes in Any Laboratory Parameter, Electrocardiogram (ECG) or Vital Signs | Changes in any laboratory parameter, ECG or vital signs were judged clinically relevant by the investigator. | Baseline and 3 days | 
| Occurences of Clinical Outcome | Occurrences of clinical outcomes including recurrent venous thrombolic event (VTE), post thrombotic syndrome (PTS), pulmonary emboli (PEs), and total and VTE related mortality objectively assessed for example by ultrasound, venography or computed chromatography (CT) scan (based on the thrombus location). Number of patients with particular clinical outcome are reported. | 3 days |