Trial Outcomes & Findings for Tolerability , PK/PD and Safety of Dabigatran Etexilate Oral Liquid Formulation in Children < 1 Year of Age (NCT NCT02223260)

NCT ID: NCT02223260

Last Updated: 2016-09-20

Results Overview

Plasma concentrations of total dabigatran, 2h and 12 h (+/-2h) post administration of dabigatran etexilate.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 8 participants
• Primary outcome timeframe: 2 hours (h) and 12h after drug administration on day 1
• Results posted on: 2016-09-20

Participant Flow

This was an open-label, multicentre, multinational, non-randomised, uncontrolled, single dose, single arm Phase IIa study.

Participant milestones

Measure	Dabigatran Etexilate The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Overall Study STARTED	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Tolerability , PK/PD and Safety of Dabigatran Etexilate Oral Liquid Formulation in Children < 1 Year of Age

Baseline characteristics by cohort

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Age, Continuous	2.912 Months STANDARD_DEVIATION 1.694 • n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	3 Participants n=93 Participants

PRIMARY outcome

Timeframe: 2 hours (h) and 12h after drug administration on day 1

Population: Pharmacokinetic set (PKS): This patient set included all treated patients who provided at least 1 PK/PD observation and had no important Protocol violations (PVs) with respect to statistical analysis of Pharmacokinetic (PK) or Pharmacodynamic (PD ) endpoints.

Plasma concentrations of total dabigatran, 2h and 12 h (+/-2h) post administration of dabigatran etexilate.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Plasma Concentrations of Total Dabigatran, 2h and 12 h (+/-2h) Post Administration of Dabigatran Etexilate 2h	120.0 ng/mL Geometric Coefficient of Variation 62.1
Plasma Concentrations of Total Dabigatran, 2h and 12 h (+/-2h) Post Administration of Dabigatran Etexilate 12h	60.4 ng/mL Geometric Coefficient of Variation 30.0

PRIMARY outcome

Timeframe: 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean activated partial thromboplastin time (aPTT) coagulation time at 2 h and 12 h (±2 h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Central Measurement: The Mean aPTT Coagulation Time at 2 h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. E2	78.9 second Standard Deviation 26.7
Central Measurement: The Mean aPTT Coagulation Time at 2 h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. E12	62.8 second Standard Deviation 27.7

PRIMARY outcome

Timeframe: 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean of Ecarin Clotting Time (ECT) coagulation time at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Central Measurement: The Mean of ECT Coagulation Time at 2 h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. E2	101 second Standard Deviation 44.3
Central Measurement: The Mean of ECT Coagulation Time at 2 h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. E12	66.9 second Standard Deviation 23.5

PRIMARY outcome

Timeframe: 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean of dTT (AntiFactor IIa activity) coagulation time at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Central Measurement: The Mean of Diluted Thrombin Time (dTT) Coagulation Time at 2 h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. E2	48.7 second Standard Deviation 24
Central Measurement: The Mean of Diluted Thrombin Time (dTT) Coagulation Time at 2 h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. E12	38.6 second Standard Deviation 8.12

PRIMARY outcome

Timeframe: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean aPTT (activated partial thromboplastin time) ratio at 2 h and 12 h (±2 h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation.

aPTT ratio= aPTT (post dose)/aPTT (baseline). The mean of aPTT ratio is presented.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Central Measurement: The Mean aPTT Ratio at 2 h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. ER2	1.86 ratio Standard Deviation 19.5
Central Measurement: The Mean aPTT Ratio at 2 h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. ER12	1.47 ratio Standard Deviation 17.7

PRIMARY outcome

Timeframe: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean Ecarin Clotting Time (ECT) ratio at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation.

ECT ratio= ECT(Post dose)/ECT(baseline), The mean of ECT ratio is presented.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Central Measurement: The Mean ECT Ratio at 2 h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. ER2	2.42 Ratio Standard Deviation 34.2
Central Measurement: The Mean ECT Ratio at 2 h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. ER12	1.63 Ratio Standard Deviation 13.8

PRIMARY outcome

Timeframe: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Central measurement: The mean of dTT (AntiFactor IIa activity) ratio at 2 h and 12 h (±2 h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation.

dTT ratio= dTT(post dose)/dTT(baseline). The mean of dTT ratio is presented.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Central Measurement: The Mean of dTT Ratio at 2h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. ER2	1.59 ratio Standard Deviation 25.4
Central Measurement: The Mean of dTT Ratio at 2h and 12h (+/-2h) Post Administration of Dabigatran Etexilate. ER12	1.26 ratio Standard Deviation 5.67

SECONDARY outcome

Timeframe: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Linear regression models were used for modeling the relationship between total dabigatran plasma concentration and coagulation parameters APTT values. For our simple regression model, R-squared is equal to the square of Pearson's coefficient of correlation. The R-squared can be between 0 and 1. R-squared =1 means a perfect fit.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
PK-PD Relationship: Relationship Between Total Dabigatran Plasma Concentration and Coagulation Parameters APTT Values.	0.752 R-Square

SECONDARY outcome

Timeframe: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Linear regression models were used for modeling the relationship between total dabigatran plasma concentration and coagulation parameters ECT values. For our simple regression model, R-squared is equal to the square of Pearson's coefficient of correlation. The R-squared can be between 0 and 1. R-squared =1 means a perfect fit.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
PK-PD Relationship: Relationship Between Total Dabigatran Plasma Concentration and Coagulation Parameters ECT Values.	0.858 R-Square

SECONDARY outcome

Timeframe: baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1

Population: PKS

Linear regression models were used for modeling the relationship between total dabigatran plasma concentration and coagulation parameters dTT (AntiFactor IIa activity) values. For our simple regression model, R-squared is equal to the square of Pearson's coefficient of correlation. The R-squared can be between 0 and 1. R-squared =1 means a perfect fit.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
PK-PD Relationship: Relationship Between Total Dabigatran Plasma Concentration and Coagulation Parameters dTT Values.	0.920 R-Square

SECONDARY outcome

Timeframe: Within two days after the administration of trial medication, up to 3 days

Population: Treated set

Percentage of patients with Incidence of all bleeding events(major, clinically relevant non-major (CRNM) & minor) during the treatment period (including the residual effect period).Bleeding events were classified as follow:

Major bleeding: 1) Fatal bleeding 2) Clinically overt bleeding associated with decrease in haemoglobin of at least 2 g/dL (20 g/L) in 24-h-period 3) Bleeding that was retroperitoneal, pulmonary, intracranial, or otherwise involved the central nervous system 4) Bleeding that required surgical intervention in an operating suite. CRNM bleeding: 1) Overt bleeding for which a blood product was administered & which was not directly attributable to the patient's underlying medical condition 2) Bleeding that required medical or surgical intervention to restore haemostasis, other than in an operating suite. Minor bleeding defined as any overt or macroscopic evidence of bleeding that did not fulfil the criteria for either major bleeding or CRNM bleeding.

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Incidence of All Bleeding Events (Major, CRNM and Minor) During the Treatment Period.	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Within two days after the administration of trial medication, up to 3 days

Population: Treated set

Percentage of patients with all adverse events (AEs) during the treatment period (including REP).

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Incidence of All AEs During the Treatment Period	0.0 percentage of participants

SECONDARY outcome

Timeframe: Day 1 (immediately after dosing)

Population: Treated set

The investigator was to provide a global clinical assessment of tolerability and acceptability of study medication by the patient.This assessment was based on 5-point scale (good, satisfactory, not satisfactory, bad, not assessable).

Outcome measures

Measure	Dabigatran Etexilate n=8 Participants The patients were orally administered a single dose of liquid formulation of dabigatran etexilate. The dose were adjusted based on an age and weight (equivalent to a 150 mg dose in adults). In case the patient could not take the full dose at once, the assigned dose could have been given as divided doses.
Global Assessment of Acceptability and Tolerability of Study Medication Good	75.0 percentage of participants
Global Assessment of Acceptability and Tolerability of Study Medication Satisfactory	12.5 percentage of participants
Global Assessment of Acceptability and Tolerability of Study Medication Not satisfactory	0.0 percentage of participants
Global Assessment of Acceptability and Tolerability of Study Medication Bad	12.5 percentage of participants
Global Assessment of Acceptability and Tolerability of Study Medication Not assessable	0.0 percentage of participants

Adverse Events

Dabigatran Etexilate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER