Clinical Trial Results:
open-label, single dose, tolerability, Pharmacokinetic/Pharmacodynamics and safety study of dabigatran etexilate given at the end of standard anticoagulant therapy in children aged less than 1 year old.
|
Summary
|
|
EudraCT number |
2014-001259-22 |
Trial protocol |
AT IT FR Outside EU/EEA |
Global end of trial date |
09 Feb 2016
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
13 Aug 2016
|
First version publication date |
13 Aug 2016
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
1160.105
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02223260 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Boehringer Ingelheim
|
||
Sponsor organisation address |
173 Binger Strasse, Ingelheim am Rhein, Germany, 55216
|
||
Public contact |
QRPE Processes and Systems Coordination
Clinical Trial Information Disclosure, Boehringer Ingelheim, 001 8002430127, clintriage.rdg@boehringer-ingelheim.com
|
||
Scientific contact |
QRPE Processes and Systems Coordination
Clinical Trial Information Disclosure, Boehringer Ingelheim, 001 8002430127, clintriage.rdg@boehringer-ingelheim.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-000081-PIP01-07 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
22 Mar 2016
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
09 Jan 2016
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
09 Feb 2016
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The aim of the study is to investigate the safety and tolerability of dabigatran etexilate solution in children aged less than 1 year, to demonstrate comparable PK/PD relationship to older children and adults and to confirm dabigatran etexilate dosing algorithm for children aged less than 1 year.
|
||
Protection of trial subjects |
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all subjects as required. An independent DMC was implemented to monitor safety and tolerability on an ongoing basis.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Mar 2015
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Canada: 3
|
||
Country: Number of subjects enrolled |
France: 1
|
||
Country: Number of subjects enrolled |
Russian Federation: 6
|
||
Worldwide total number of subjects |
10
|
||
EEA total number of subjects |
1
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
1
|
||
Infants and toddlers (28 days-23 months) |
9
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||
|
Recruitment
|
|||||||
Recruitment details |
Before inclusion into the trial, all patients had to complete the planned treatment with either Low molecular weight heparin(LMWH),Unfractionated heparin(UFH), or oral anticoagulation for Venous thrombotic event (VTE) prior to intake of the single dose of study medication. | ||||||
|
Pre-assignment
|
|||||||
Screening details |
All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that they (the subjects) met all strictly implemented inclusion/exclusion criteria. Subjects were not to be entered to trial treatment if any one of the specific entry criteria were violated | ||||||
|
Period 1
|
|||||||
Period 1 title |
Treatment period (overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
|
||||||
Blinding used |
Not blinded | ||||||
Blinding implementation details |
This is an Open-label, multicentre, non-randomised, uncontrolled, single-arm, single dose study.
|
||||||
|
Arms
|
|||||||
|
Arm title
|
Dabigatran etexilate | ||||||
Arm description |
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. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Dabigatran etexilate
|
||||||
Investigational medicinal product code |
|||||||
Other name |
|||||||
Pharmaceutical forms |
Oral liquid
|
||||||
Routes of administration |
Oral use
|
||||||
Dosage and administration details |
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).
|
||||||
|
|||||||
| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Baseline characteristics are based on the patients who were randomised after successfully completing the screening period and received at least one dose of the trial medication. |
|||||||
|
|||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||
Reporting group title |
Dabigatran etexilate
|
||||||||||||||||||||||||||||||||||||
Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Dabigatran etexilate
|
||
Reporting group description |
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. | ||
|
|||||||||||||
End point title |
Plasma concentrations of total dabigatran at 2h and 12 h (+/-2h) post administration of dabigatran etexilate [1] | ||||||||||||
End point description |
Plasma concentrations of total dabigatran at 2h and 12 h (+/-2h) post administration of dabigatran etexilate.
Pharmacokinetic set (PKS): This patient set included all treated patients who provided at least 1 PK/PD observation and had no important protocol violations(PV's) with respect to statistical analysis of PK or PD (Pharmacodynamic) endpoints.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
2 hours (h) and 12h after drug administration on day 1
|
||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis were tested. |
|||||||||||||
|
|||||||||||||
| Notes [2] - PKS |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Central measurement: The mean aPTT coagulation time at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. [3] | ||||||||||||
End point description |
Central measurement: The mean aPTT (activated partial thromboplastin time) coagulation time at 2 h and 12 h (±2 h) post administration of dabigatran etexilate. Standard deviation is actually the Coefficient of Variation.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
2 h and 12 h after dosing on day 1
|
||||||||||||
| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis were tested. |
|||||||||||||
|
|||||||||||||
| Notes [4] - PKS |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Central measurement: The mean of ECT coagulation time at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. [5] | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
2 h and 12 h after dosing on day 1
|
||||||||||||
| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis were tested. |
|||||||||||||
|
|||||||||||||
| Notes [6] - PKS |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Central measurement: The mean of diluted thrombin time (dTT) coagulation time at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. [7] | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
2 h and 12 h after dosing on day 1
|
||||||||||||
| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis were tested. |
|||||||||||||
|
|||||||||||||
| Notes [8] - PKS |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Central measurement: The mean aPTT ratio at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. [9] | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
baseline (0.5 h before intake of study medication), 2 h and 12 h after dosing on day 1
|
||||||||||||
| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis were tested. |
|||||||||||||
|
|||||||||||||
| Notes [10] - PKS |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Central measurement: The mean ECT ratio at 2 h and 12h (+/-2h) post administration of dabigatran etexilate. [11] | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1
|
||||||||||||
| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis were tested. |
|||||||||||||
|
|||||||||||||
| Notes [12] - PKS |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Central measurement: The mean of dTT ratio at 2h and 12h (+/-2h) post administration of dabigatran etexilate. [13] | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1
|
||||||||||||
| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis were tested. |
|||||||||||||
|
|||||||||||||
| Notes [14] - PKS |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
PK-PD relationship: Relationship between total dabigatran plasma concentration and coagulation parameters aPTT values. | ||||||||
End point description |
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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1
|
||||||||
|
|||||||||
| Notes [15] - PKS |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
PK-PD relationship: Relationship between total dabigatran plasma concentration and coagulation parameters ECT values. | ||||||||
End point description |
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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1
|
||||||||
|
|||||||||
| Notes [16] - PKS |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
PK-PD relationship: Relationship between total dabigatran plasma concentration and coagulation parameters dTT values. | ||||||||
End point description |
Linear regression models were used for modeling the relationship between total dabigatran plasma concentration and coagulation parameters dTT (AntiFactor IIa activity) ratio. 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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
baseline (0.5 h before intake of study medication), 2 h, and 12 h after dosing on day 1
|
||||||||
|
|||||||||
| Notes [17] - PKS |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Incidence of all bleeding events (major, CRNM and minor) during the treatment period. | ||||||||
End point description |
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.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Within two days after the administration of trial medication, up to 3 days
|
||||||||
|
|||||||||
| Notes [18] - Treated set |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Incidence of all AEs during the treatment period | ||||||||
End point description |
Percentage of patients with all adverse events during the treatment period (including REP).
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Within two days after the administration of trial medication, up to 3 days
|
||||||||
|
|||||||||
| Notes [19] - Treated set |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||
End point title |
Global assessment of acceptability and tolerability of study medication | ||||||||||||||||||
End point description |
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).
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Day 1 (immediately after dosing)
|
||||||||||||||||||
|
|||||||||||||||||||
| Notes [20] - Treated set |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||
|
Adverse events information [1]
|
|||||||||||
Timeframe for reporting adverse events |
Within two days after the administration of trial medication, up to 3 days.
|
||||||||||
Assessment type |
Systematic | ||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||
Dictionary name |
MedDRA | ||||||||||
Dictionary version |
18.1
|
||||||||||
|
Reporting groups
|
|||||||||||
Reporting group title |
dabigatran etexilate
|
||||||||||
Reporting group description |
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. | ||||||||||
|
|||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||
|
|||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: In this study no non-serious adverse events data documented, thus no non-serious adverse events are reported. |
|||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
