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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01083732
First Posted: March 10, 2010
Last Update Posted: December 28, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Boehringer Ingelheim
  Purpose
To investigate the safety and tolerability of dabigatran etexilate solution in children and to obtain preliminary pharmacokinetic/pharmacodynamic data

Condition Intervention Phase
Venous Thromboembolism Drug: dabigatran etexilate Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: Single Dose Open-label PK/PD, Safety and Tolerability Study of Dabigatran Etexilate Mesilate Given at the End of Standard Anticoagulant Therapy in Successive Groups of Children Aged 2 Years to Less Than 12 Years Followed by 1 Year to Less Than 2 Years

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ]
    Plasma concentration of total dabigatran (SUM BIBR 953 ZW)

  • 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 ]
    Plasma concentration of free dabigatran (BIBR 953 ZW)

  • Plasma Concentration of Unchanged Dabigatran Etexilate (BIBR 1048 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 ]

    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.


  • 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 ]
    Plasma concentration of metabolite BIBR 951 BS

  • 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 ]
    Plasma concentration of metabolite BIBR 1087 SE

  • Central Measurement of Activated Partial Thromboplastin Time (aPTT) at Predose and 2 and 10 h After Intake of Study Medication. [ Time Frame: at predose and 2 and 10 h after intake of study medication. ]
    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.

  • Central Measurement of Ecarin Clotting Time (ECT) at Predose and 2 and 10 h After Intake of Study Medication. [ Time Frame: at predose and 2 and 10 h after intake of study medication. ]
    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

  • Central Measurement of Diluted Thrombin Time (dTT) at Predose and 2 and 10 h After Intake of Study Medication. [ Time Frame: at predose and 2 and 10 h after intake of study medication. ]
    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

  • Cmax (Maximum Measured Concentration of Total Dabigatran in Plasma) [ Time Frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate ]
    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).

  • Tmax (Time From Dosing to Maximum Measured Concentration of Total Dabigatran in Plasma) [ Time Frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate ]

    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).


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

    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).


  • Cmax (Maximum Measured Concentration of Free Dabigatran in Plasma) [ Time Frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate ]
    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).

  • Tmax (Time From Dosing to Maximum Measured Concentration of Free Dabigatran in Plasma) [ Time Frame: At 1 hour (h), 2 h, 4 h, 6 h, and 10 h after single administration of dabigatran etexilate ]

    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).


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

    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).


  • Percentage of Patients With Incidence of Any Bleeding Events (Major, Clinically Relevant Non-major (CRNM) and Minor) During the Treatment Period. [ Time Frame: Up to 6 days ]
    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.


Secondary Outcome Measures:
  • Percentage of Patients With Any Adverse Events During the Treatment Period [ Time Frame: Up to 6 days ]
    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.

  • Global Assessment of Tolerability of Study Medication- Taste Assessment [ Time Frame: Day 1 (immediately after dosing) ]
    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.

  • Percentage of Patients With Changes in Laboratory and Clinical Parameters Such as Liver Enzymes and Physical Examination [ Time Frame: During the treatment period, Up to 6 days ]

    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.


  • Global Assessment of Tolerability of Study Medication [ Time Frame: Day 1 (immediately after dosing) ]
    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).


Enrollment: 18
Study Start Date: March 2010
Study Completion Date: February 2016
Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dabigatran etexilate
treatment with dabigatran oral solution as a single dose
Drug: dabigatran etexilate
Experimental dose chosen based on age and weight

Detailed Description:
Purpose:
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   1 Year to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. males or females 1 to less than 12 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 (if applicable)

Exclusion criteria:

  1. weight less than 9 kg
  2. conditions associated with increased risk of bleeding
  3. patients who have any condition that would not allow safe participation in study Note: Further exclusion criteria apply
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01083732


Locations
Canada, Ontario
Boehringer Ingelheim Investigational Site
Ottawa, Ontario, Canada
Italy
Boehringer Ingelheim Investigational Site
Roma, Italy
Lithuania
Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
Russian Federation
Boehringer Ingelheim Investigational Site
Kazan, Russian Federation
Switzerland
Boehringer Ingelheim Investigational Site
Zürich, Switzerland
Thailand
Boehringer Ingelheim Investigational Site
Bangkok, Thailand
Boehringer Ingelheim Investigational Site
Khon Kaen, Thailand
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01083732     History of Changes
Other Study ID Numbers: 1160.89
2009-013618-29 ( EudraCT Number: EudraCT )
First Submitted: March 8, 2010
First Posted: March 10, 2010
Results First Submitted: August 17, 2016
Results First Posted: December 28, 2016
Last Update Posted: December 28, 2016
Last Verified: November 2016

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Dabigatran
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants