This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Tolerability , PK/PD and Safety of Dabigatran Etexilate Oral Liquid Formulation in Children < 1 Year of Age (NCT02223260), a na phase 2 study. The primary outcome is Plasma Concentrations of Total Dabigatran, 2h and 12 h (+/-2h) Post Administration of Dabigatran Etexilate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02223260 |
| Phase | Phase 2 |
| Condition | Venous Thromboembolism |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 8 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
Children aged less than 1 year with venous thromboembolism were the population of interest. The study enrolled 8 participants. The primary pharmacokinetic analysis population was defined as treated participants with at least 1 pharmacokinetic or pharmacodynamic observation and no important protocol violations affecting those analyses.
Intervention
Participants received dabigatran etexilate as an oral liquid formulation in a single dose. The study was open label, so treatment was not masked.
Comparator
There was no concurrent control group. The registry describes a single-group study, not a randomized comparison. Older children and adults are mentioned as reference populations in the study aim, but a direct comparison with them is not described in the registry record.
Primary question
The primary endpoint was total dabigatran plasma concentration at 2 hours and 12 hours after dosing, with a permitted timing window of +/-2 hours for the 12-hour measurement. The study aimed to assess pharmacokinetics, tolerability, and safety, and to examine whether the pharmacokinetic and pharmacodynamic relationship was comparable to that in older children and adults. Numerical primary-endpoint results are not reported in the registry record.
3. Trial Design
This was a Phase 2, open-label, single-group study of dabigatran etexilate oral liquid in children aged less than 1 year. The registry lists enrollment of 8 and describes a single dose given at the end of standard anticoagulant therapy. The study status is completed. Its recorded start was 2014-09 and its primary completion was 2016-01.
There was no random allocation and no masking. Because every listed participant was in the dabigatran group and no concurrent control arm is described, the design does not support a like-for-like comparison between treatment groups. The registry’s study aim refers to evaluating whether the pharmacokinetic and pharmacodynamic relationship resembles that in older children and adults, but no corresponding comparison group or numerical comparative results are reported in the registry record.
The main endpoint concerns total dabigatran plasma concentrations at two post-dose times on day 1. The registry also lists pharmacokinetic and pharmacodynamic relationships involving coagulation measures, bleeding events, adverse events, and acceptability and tolerability. It reports 13 outcome measures, but numerical results for the primary endpoint are not reported in the registry record.
The registry record does not report a sample-size justification, a detailed statistical analysis plan, or interim analyses. Those omissions limit what can be concluded about the original design rationale and planned inferential methods. The study’s single-dose setting also defines the scope of its evidence: it concerns measurements and safety observations associated with that study dose, not a comparison of ongoing treatment strategies.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: This was an open-label, multicentre, multinational, non-randomised, uncontrolled, single dose, single arm Phase IIa study.
Overall Study
| Stage | Dabigatran Etexilate |
|---|---|
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: 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.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Treated set (TS): the treated set included 8 patients who were dispensed study medication and were documented to have taken at least 1 dose of trial medication.
| Characteristic | Unit | Dabigatran Etexilate |
|---|---|---|
| Participants analysed | 8 | |
| Age, Continuous | Months | 2.912 (SD 1.694) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Plasma Concentrations of Total Dabigatran, 2h and 12 h (+/-2h) Post Administration of Dabigatran Etexilate, measured over 2 hours (h) and 12h after drug administration on day 1.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | ng/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint measures total dabigatran in plasma at 2 hours and 12 hours after administration on day 1; the 12-hour time point allows a window of +/-2 hours. Concentration is expressed in ng/mL. The registry specifies that the endpoint is summarized by a geometric mean and a geometric coefficient of variation, and identifies the pharmacokinetic set as the analysis population.
Pharmacokinetic measurements describe how drug concentrations change over time after administration. Measuring concentration at specified times can characterize exposure at those moments and can contribute to assessing a dosing approach. The geometric mean is a way to summarize positive, often right-skewed concentration data on a multiplicative scale. The geometric coefficient of variation describes relative variability on that scale; it is not the same as a standard deviation expressed in the original concentration units.
The endpoint is therefore a measure of drug exposure, not a direct measure of clinical benefit. The registry’s stated study aims also include safety, tolerability, and comparison of pharmacokinetic and pharmacodynamic relationships with those in older children and adults. However, numerical concentration results and the estimated geometric variability are not reported in the registry record, so the observed exposure and its precision cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the endpoint and its measurement schedule but does not report numerical primary-endpoint values. In particular, it does not give the geometric mean concentration or geometric coefficient of variation at either post-dose time. Without those results, the observed concentration levels, their variability, and the precision of the estimates cannot be evaluated. No primary-endpoint confidence interval or test result is reported in the registry record.
The study’s aim includes assessing whether the pharmacokinetic and pharmacodynamic relationship is comparable to that in older children and adults. An aim is not itself evidence that comparability was demonstrated. The registry record does not report the estimates, comparison method, or uncertainty needed to evaluate that question. It also describes no concurrent comparator group, so the study is not a randomized treatment comparison.
The adverse-event listing records 0 serious adverse events among 8 participants at risk and 0 other adverse events among 8 participants at risk. These are the counts in the registry record; they do not establish that an event is impossible or that risk is absent. In a study of this size, a lack of recorded events gives limited information about uncommon harms. Deaths are not reported in the registry record. The listed safety counts should also be kept distinct from the secondary outcome descriptions: bleeding events and all adverse events are named as outcomes, but their detailed numerical results are not reported in the registry record.
The registry lists 13 outcome measures and 0 analysis entries. That record does not supply inferential results for the primary endpoint or a detailed account of how outcomes were analyzed. It is therefore not possible to assess statistical significance, estimate a treatment effect, or judge whether the study met a prespecified success criterion from the posted information. The absence of numerical results should not be read as evidence of either a positive or a negative finding.
The appropriate interpretation is narrow: the registry describes a single-dose pharmacokinetic and safety study, with a defined primary measurement schedule and a small enrollment. It does not provide the numerical primary results needed to characterize exposure or determine how precisely it was estimated. The study’s stated objectives should be treated as questions the design sought to address, not conclusions established by the registry record.
9. Statistical Methods Explained
The registry describes a pharmacokinetic endpoint summarized with a geometric mean and geometric coefficient of variation. It does not report numerical results, confidence intervals, hypothesis tests, or the full statistical analysis plan. The concepts below explain how such methods are generally interpreted; they do not assert which additional procedures were used in this study.
Why use a geometric mean for concentrations?
Concentration data are positive and can have a distribution with a long upper tail. In such settings, a small number of relatively high observations can affect an arithmetic mean substantially. A geometric mean summarizes values on a multiplicative scale: conceptually, values are transformed to a logarithmic scale, averaged there, and transformed back. It can be useful when differences between observations are more naturally understood as relative changes than as fixed increments.
A geometric mean is not the same as a median, and it does not show the range of individual observations. A summary alone cannot reveal whether participants’ concentrations were closely clustered or widely spread. The geometric coefficient of variation is intended to describe relative spread on the multiplicative scale. Its interpretation depends on the distribution and analysis conventions, so it should be read alongside the study’s methods and, where available, individual-level plots or uncertainty intervals. Numerical values for either summary are not reported in the registry record.
What do the sampling times contribute?
The primary endpoint specifies plasma concentration at 2 hours and 12 hours after administration on day 1, with a +/-2-hour window for the 12-hour measurement. Specified sampling times make observations interpretable relative to dose timing. They do not, on their own, describe the complete concentration-time curve. A limited set of scheduled measurements cannot establish every feature of drug absorption and elimination without further measurements and an appropriate pharmacokinetic model. The registry record does not give numerical concentrations or describe such a model.
The pharmacokinetic set is defined as treated participants who had at least 1 pharmacokinetic or pharmacodynamic observation and no important protocol violations with respect to analysis of those endpoints. This population definition helps distinguish the intended analysis set from all enrolled participants. The registry does not report how many participants met this definition or whether any observations were excluded.
How should pharmacokinetic and pharmacodynamic relationships be understood?
Pharmacokinetics concerns drug concentrations; pharmacodynamics concerns the relationship between exposure and a biological response. The listed secondary outcomes describe relationships between total dabigatran plasma concentration and APTT, ECT, and dTT coagulation parameters. In general, examining such relationships can help characterize how measured exposure corresponds to measured changes in laboratory parameters. The registry record does not provide the numerical relationship estimates, the time points used for those analyses, or their uncertainty, so their strength and precision cannot be assessed.
What would a confidence interval tell a reader?
In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision under those assumptions; a wider interval indicates more uncertainty. Its interpretation is not a guarantee that the true value lies within a particular observed interval, nor does it replace attention to the study design and analysis population. No confidence interval for the primary endpoint is reported in the registry record.
Why can variability matter in a small pharmacokinetic study?
General statistical reasoning: greater between-participant variability makes an average less precise when the amount of information is fixed. Concentration measurements can vary for biological and measurement-related reasons, and highly variable data can make a group summary less representative of individual observations. The geometric coefficient of variation is one way to describe relative variability, but the registry record does not report its value. Consequently, the precision of the concentration summaries cannot be judged from the posted results.
Over-dispersion is a general concern when observed variability exceeds what a chosen statistical model assumes. If a model understates variability, its standard errors can be too small and its intervals or tests can appear more certain than warranted. That concern is a general methodological explanation, not a finding about this study: the registry record does not report a model fit, an over-dispersion assessment, or numerical outcome data from which to make one.
The record also does not report the distributional assumptions, handling of repeated measurements, covariate adjustment, or method for uncertainty estimation. These details matter when interpreting estimates, especially in a pharmacokinetic analysis with more than one time point. They should not be inferred from the endpoint label alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures. The listed secondary outcomes include relationships between concentration and three coagulation parameters, bleeding events, all adverse events, and global acceptability and tolerability. Assessing several outcomes raises a general multiplicity issue: when many statistical questions are tested, the chance of at least one apparently unusual result can increase if each is treated as an independent confirmatory test. A prespecified hierarchy or adjustment can address some multiplicity concerns, but a multiplicity strategy is not reported in the registry record.
The registry record lists 0 analysis entries and does not report numerical primary-endpoint results. It does not state which outcomes were treated as confirmatory, whether any adjustment was made, or how any testing hierarchy was defined. Therefore, no conclusion about statistical significance across outcomes can be drawn from the posted information.
The primary pharmacokinetic population is defined as treated participants with at least 1 pharmacokinetic or pharmacodynamic observation and no important protocol violations relevant to those analyses. The registry does not report the number included in that set, the number of missing measurements, the reasons for missingness, or the method used to handle missing observations. It also does not report whether all enrolled participants contributed to every safety or secondary outcome assessment.
These omissions affect interpretation because missing observations can reduce precision, and the consequences depend on why data are missing and how the analysis handles them. The registry record does not permit an assessment of whether missing data could have altered the results. A detailed missing-data plan and analysis-population flow are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Dabigatran Etexilate | 0 | 8 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dabigatran Etexilate | 0 of 8 |
The adverse-event listing records 0 serious adverse events among 8 participants at risk in the dabigatran etexilate group. It also records 0 other adverse events among 8 participants at risk. These counts describe the registry’s recorded observations; they are not estimates of the probability of an event in a broader population and do not establish that events cannot occur.
With limited enrollment, an event that was not observed can still be possible, and the record does not quantify the uncertainty around these counts. The registry lists incidence of all bleeding events and incidence of all adverse events as secondary outcomes, but detailed results for those outcomes are not reported in the registry record. Deaths are not reported in the registry record. The safety listing should therefore be read as a count of recorded events in this study, not as a comprehensive estimate of safety risk.
12. What the Result Does, and Does Not, Mean
The study addresses a focused pharmacokinetic and safety question: it evaluates a single dose of dabigatran etexilate oral liquid in children aged less than 1 year and specifies plasma concentration measurements at two post-dose times. It also lists pharmacodynamic relationships, bleeding, adverse events, and medication acceptability and tolerability among its outcomes. This design can describe observations in the study group if numerical results are reported.
The registry record does not report numerical primary-endpoint results. It therefore does not show the observed concentrations, the degree of variability, or the precision of those measurements. Although the study aim mentions comparison of pharmacokinetic and pharmacodynamic relationships with older children and adults, the registry record does not report numerical comparison results or describe a concurrent older age group. The aim cannot be treated as evidence that the relationships were comparable.
The safety listing records no serious or other adverse events in the exposed group, but those counts do not demonstrate absence of risk. Limited enrollment provides little information about rare outcomes, and the registry does not report a confidence interval or a more detailed safety analysis. The deaths field is not reported in the registry record.
These limitations do not establish that the study’s objectives were unmet; rather, the posted information is insufficient to determine how the primary endpoint or the stated comparison objective turned out. Nor does a single-group, open-label, single-dose design answer a randomized comparative-effectiveness question. The findings that can be attributed to the registry record are its design, its intended measurements, its enrollment, and its reported event counts. Conclusions about dosing, clinical benefit, or the comparative safety of treatments are not established by these registry entries.
13. Why This Trial Matters Statistically
This study is statistically distinctive because it focuses on pharmacokinetic measurement in children aged less than 1 year rather than on a randomized comparison of treatment groups. Its primary endpoint uses concentration measurements at specified times and summarizes them with a geometric mean and geometric coefficient of variation. Those choices are relevant to the distributional properties of concentration data and to how exposure and variability would be described.
The registry also identifies a pharmacokinetic set rather than defining the primary analysis solely by enrollment. Such a population definition matters because eligibility for analysis depends on having at least 1 relevant observation and avoiding important protocol violations. However, the number included in that set and the handling of missing observations are not reported in the registry record, so the practical effect of the definition cannot be assessed.
The listed secondary outcomes span pharmacodynamic relationships, bleeding, adverse events, and tolerability. This breadth can be useful for describing several dimensions of a study, while also making prespecification and multiplicity management important. The registry does not report a multiplicity strategy or detailed analysis plan.
Finally, the gap between a clearly described measurement objective and absent numerical primary results is itself important for statistical interpretation. Design information can explain what the study sought to measure, but it cannot substitute for estimates and uncertainty. Without those results, readers cannot evaluate exposure, variability, or the precision of the pharmacokinetic findings. The registry entry therefore has value as a description of study design and intended outcomes, while leaving the central numerical question unresolved in the posted record.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry describes a single-group, open-label study with a single dose. There is no concurrent comparator and no random allocation, limiting the design’s ability to support comparative conclusions. The stated interest in relationships comparable to older children and adults is not accompanied by a reported comparison group or numerical comparison results in the registry record.
Enrollment was 8, and the registry does not report numerical primary-endpoint results. It therefore offers no concentration estimates, variability estimates, or uncertainty intervals with which to judge the precision of the main pharmacokinetic assessment. The registry also does not report how many participants met the defined pharmacokinetic set criteria or whether measurements were missing or excluded.
The record does not report a detailed statistical analysis plan, sample-size justification, multiplicity approach, missing-data method, or interim analyses. It also does not report numerical results for the listed pharmacodynamic, bleeding, and tolerability outcomes. These gaps prevent an assessment of the full outcome profile and the statistical methods actually applied.
The safety listing contains no recorded serious or other adverse events, but a limited study cannot characterize uncommon events precisely. Deaths are not reported in the registry record. These limitations are specific to the design and the information recorded; they should not be converted into conclusions about unreported results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Tolerability , PK/PD and Safety of Dabigatran Etexilate Oral Liquid Formulation in Children < 1 Year of Age — NCT02223260.
- Registry record last updated 2016-09-20; status last verified 2016-07.
- Results first posted 2016-09-20.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes a completed Phase 2, open-label, single-group study of a single dose of dabigatran etexilate oral liquid in children aged less than 1 year with venous thromboembolism. Enrollment was 8. The primary endpoint was total dabigatran plasma concentration at 2 hours and 12 hours after dosing on day 1, with a +/-2-hour window for the 12-hour measurement. The endpoint was to be summarized by geometric mean and geometric coefficient of variation in a defined pharmacokinetic set.
The study also listed pharmacodynamic relationships, bleeding events, adverse events, and acceptability and tolerability outcomes. The adverse-event listing records 0 serious and 0 other adverse events among 8 at risk; deaths are not reported in the registry record. Numerical primary-endpoint results, a detailed analysis plan, and a multiplicity or missing-data approach are not reported in the registry record.