Safety and Tolerability of Dabigatran Etexilate in Adolescents

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00844415

Enrollment

Registered

2009-02-16

Start date

2009-06-01

Completion date

Unknown

Last updated

2025-02-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Venous Thromboembolism

Brief summary

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

Interventions

DRUGdabigatran etexilate

2.14 mg/kg BID to a max 150 mg BID

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to 17 Years

Healthy volunteers

Inclusion criteria

1. males or females 12 to less than 18 years of age 2. objective diagnosis of primary VTE 3. completion of planned treatment course with LMWH or OAC for primary VTE 4. written informed consent by parent (legal guardian) and patient assent

Exclusion criteria

1. weight less than 32 kg 2. conditions associated with increased risk of bleeding 3. severe renal dysfunction or requirement for dialysis 4. active infective endocarditis 5. hepatic disease 6. pregnant females or females not using medically accepted contraceptive method 7. anemia or thrombocytopenia 8. use of prohibited or restricted drug within previous week 9. received investigational drug within past 30 days 10. unreliable patients or patients who have any condition that would not allow safe participation in study

Design outcomes

Primary

Measure	Time frame	Description
TT Locally Measured	Day 3	Measurement of TT was performed locally and centrally by Hemoclot Thrombin Inhibitor clotting assay.
Number of Patients With Bleeding Events (Major and Minor)	From Screening until 30 days after first drug administration (end of trial visit)	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.
Number of Patients With Adverse Events	From Screening until 30 days after first drug administration (end of trial visit)	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.
Plasma Concentration of Free Dabigatran	3 days	Plasma concentration of free dabigatran measured at 72 hours after first dose
Plasma Concentration of Total Dabigatran	Day 3	Plasma concentration of total dabigatran measured at 72 hours after first dose
Thrombin Time (TT) Centrally Measured	Day 3	Measurement of TT was performed locally and centrally by Hemoclot Thrombin Inhibitor clotting assay.

Secondary

Measure	Time frame	Description
aPTT Locally Measured	Day 3	Measurement of aPTT was performed locally and centrally using validated assays.
Ecarin Clotting Time (ECT)	Day 3	Measurement of ECT was performed locally and centrally using validated assays. Descriptive statistics is only performed for the centrally measured ECT.
Patients With Clinically Relevant Changes in Any Laboratory Parameter, Electrocardiogram (ECG) or Vital Signs	Baseline and 3 days	Changes in any laboratory parameter, ECG or vital signs were judged clinically relevant by the investigator.
Occurences of Clinical Outcome	3 days	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.
Activated Partial Thromboplastin Time (aPTT) Centrally Measured	Day 3	Measurement of aPTT was performed locally and centrally using validated assays.

Countries

Canada

Participant flow

Participants by arm

Arm	Count
All Patients Dabigatran was administered twice daily for three consecutive days (total 6 doses). All patients received an initial oral dose of 1.71mg/kg of dabigatran (80 percent of the adult dose of 150 mg/70 kg adjusted for the patient's weight). Based on thrombin time (TT) and clinical assessment, the dose was adjusted to the target dose of 2.14 mg/kg of dabigatran (100 percent of the adult dose adjusted for the patient's weight). Three patients received 75 mg dabigatran (first dose) followed by 100 mg twice daily (BID). Three patients took dabigatran 100 mg (first dose) followed by 125 mg BID. Two patients received a dose of 125 mg dabigatran followed by 150 mg BID. One patient received only a single dose of dabigatran (75 mg).	9
Total	9

Arm

Count

All Patients

Dabigatran was administered twice daily for three consecutive days (total 6 doses). All patients received an initial oral dose of 1.71mg/kg of dabigatran (80 percent of the adult dose of 150 mg/70 kg adjusted for the patient's weight). Based on thrombin time (TT) and clinical assessment, the dose was adjusted to the target dose of 2.14 mg/kg of dabigatran (100 percent of the adult dose adjusted for the patient's weight). Three patients received 75 mg dabigatran (first dose) followed by 100 mg twice daily (BID). Three patients took dabigatran 100 mg (first dose) followed by 125 mg BID. Two patients received a dose of 125 mg dabigatran followed by 150 mg BID. One patient received only a single dose of dabigatran (75 mg).

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	All Patients
Age, Continuous	15.7 years STANDARD_DEVIATION 1.3
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	3 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	2 / 9
serious Total, serious adverse events	0 / 9

Outcome results

Primary

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.

Time frame: From Screening until 30 days after first drug administration (end of trial visit)

Population: TS

Arm	Measure	Group	Value (NUMBER)
All Patients	Number of Patients With Adverse Events	DRAEs on-treatment	2 Participants
All Patients	Number of Patients With Adverse Events	SAEs on-treatment	0 Participants
All Patients	Number of Patients With Adverse Events	DRAEs post-treatment	0 Participants
All Patients	Number of Patients With Adverse Events	SAEs post-treatment	1 Participants

Primary

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.

Time frame: From Screening until 30 days after first drug administration (end of trial visit)

Population: Treated set (TS). This patient set includes all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.

Arm	Measure	Value (NUMBER)
All Patients	Number of Patients With Bleeding Events (Major and Minor)	0 Participants

Primary

Plasma Concentration of Free Dabigatran

Plasma concentration of free dabigatran measured at 72 hours after first dose

Time frame: 3 days

Population: Treated Set. Descriptive statistics for the concentration measurement could only be calculated for the subgroups of patients receiving the same sequence of doses. Statistics were only reported for groups with at least 3 patients (non-sparse data).

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
All Patients	Plasma Concentration of Free Dabigatran	Patients with 75mg dose followed by 100mg (N=3)	28.0 ng/ml	Geometric Coefficient of Variation 12.8
All Patients	Plasma Concentration of Free Dabigatran	Patients with 100mg dose followed by 125mg (N=3)	41.6 ng/ml	Geometric Coefficient of Variation 66.5

Primary