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

NCT01083732 | Completed Phase 2 Results

• 2 other identifiers: 1160.892009-013618-29
• Study Type: interventional
• Target: 18
• Locations: 6 countries
• Sites: 7

Brief Summary

To investigate the safety and tolerability of dabigatran etexilate solution in children and to obtain preliminary pharmacokinetic/pharmacodynamic data

Conditions

Venous Thromboembolism

Outcome Measures

Primary Outcomes (15)

• Plasma Concentration of Total Dabigatran (SUM BIBR 953 ZW)

  Plasma concentration of total dabigatran (SUM BIBR 953 ZW)

  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 free dabigatran (BIBR 953 ZW)

  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)

  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.

  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 951 BS

  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

  Plasma concentration of metabolite BIBR 1087 SE

  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

• Central Measurement of Activated Partial Thromboplastin Time (aPTT) 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.

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

• Central Measurement of Ecarin Clotting Time (ECT) 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

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

• Central Measurement of Diluted Thrombin Time (dTT) 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

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

• Cmax (Maximum Measured Concentration of Total Dabigatran in Plasma)

  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).

  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)

  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).

  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)

  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).

  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)

  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).

  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)

  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).

  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)

  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).

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

• Percentage of Patients With Incidence of Any Bleeding Events (Major, Clinically Relevant Non-major (CRNM) and Minor) During the Treatment Period.

  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.

  Up to 6 days

Secondary Outcomes (4)

• Percentage of Patients With Any Adverse Events During the Treatment Period

  Up to 6 days

• Global Assessment of Tolerability of Study Medication- Taste Assessment

  Day 1 (immediately after dosing)

• Percentage of Patients With Changes in Laboratory and Clinical Parameters Such as Liver Enzymes and Physical Examination

  During the treatment period, Up to 6 days

• Global Assessment of Tolerability of Study Medication

  Day 1 (immediately after dosing)

Study Arms (1)

dabigatran etexilate

EXPERIMENTAL

treatment with dabigatran oral solution as a single dose

Drug: dabigatran etexilate

Interventions

dabigatran etexilate DRUG

Experimental dose chosen based on age and weight

dabigatran etexilate

Eligibility Criteria

• Age: 1 Year - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• weight less than 9 kg
• conditions associated with increased risk of bleeding

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (7)

Boehringer Ingelheim Investigational Site

Ottawa, Ontario, Canada

Location

Boehringer Ingelheim Investigational Site

Roma, Italy

Location

Boehringer Ingelheim Investigational Site

Vilnius, Lithuania

Location

Boehringer Ingelheim Investigational Site

Kazan', Russia

Location

Boehringer Ingelheim Investigational Site

Zurich, Switzerland

Location

Boehringer Ingelheim Investigational Site

Bangkok, Thailand

Location

Boehringer Ingelheim Investigational Site

Khon Kaen, Thailand

Location

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

Dabigatran

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2010
• First Posted: March 10, 2010
• Study Start: March 1, 2010
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: December 28, 2016
• Results First Posted: December 28, 2016

Record last verified: 2016-11

Locations

CA (1); RU (1); TH (2); LI (1); CH (1); IT (1)