Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Pediatrics Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Pediatrics Subjects (NCT00652028), a non-randomized phase 2 study. The primary outcome is Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t).

2. Clinical Question

The stated objective was to characterize dexmedetomidine’s pharmacokinetic and pharmacodynamic profile in pediatric subjects. Pharmacokinetics concerns how drug concentration changes over time; pharmacodynamics concerns the relationship between exposure and observed effects. Those concepts frame the study question, but the registry record does not provide numerical pharmacokinetic or pharmacodynamic findings for the endpoint described.

The study enrolled 69 participants and evaluated four dose levels. Because the design was non-randomized and single-group, the central question is characterization across dose levels, not a randomized estimate of the effect of dexmedetomidine relative to a control treatment. The registry record does not report a separate comparator regimen or a control group.

3. Trial Design

This was a phase II, open-label, multicenter, escalating-dose study. It was non-randomized and described as a single-group study, with four dose levels identified in the registry record. Enrollment was 69. The record lists the study as completed, with a start date of 2008-11 and primary completion in 2010-04.

The target population was intubated and mechanically ventilated pediatric subjects ages 2 through under 17 years. The study objective concerned dexmedetomidine given by intravenous loading dose followed by continuous intravenous infusion. The intervention listing also names midazolam and fentanyl, but their timing, use, and relationship to the dose-level groups are not reported in the registry record.

Open-label means treatment assignment was not masked. A non-randomized escalating-dose design can describe observations made at the studied dose levels, but it does not create the protection against systematic differences that random assignment is intended to provide. The dose-level groups therefore should not be read as randomized treatment and control arms. The registry record does not report further details of how participants entered each dose level or whether specific escalation decisions governed enrollment.

The primary pharmacokinetic and pharmacodynamic population was defined as participants who received study drug infusion for at least 5 hours and had available pharmacokinetic data. This is narrower than enrollment as a whole if any enrolled participants did not meet those criteria, but the number meeting the definition is not reported in the registry record.

Additional protocol details, including the sample-size justification, interim analyses, and statistical plan, are not reported in the registry record. The record identifies 9 outcome measures, but numerical findings for the primary endpoint are not reported. Accordingly, the design can be described, while conclusions about the size, precision, or direction of pharmacokinetic findings cannot be drawn from the registered information summarized in this record.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Evaluable Population: Participants who received study drug infusion for at least 5 hours and had available PK data were included in the full evaluable population. This was the primary population for pharmacokinetic (PK) and pharmacodynamic (PD) analyses.

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: Safety Population: Participants who received any amount of study drug were included in the Safety Population

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t), measured over ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI..

The primary endpoint is the area under the concentration-time curve from time zero to the time of the last measurable concentration, abbreviated AUC0-t. Its unit is picograms*hr/mL. It is a continuous pharmacokinetic measure intended to summarize dexmedetomidine exposure across the period for which measurable concentration data are available.

General: A concentration-time curve tracks measured drug concentration over time. The area beneath that curve combines information across the measurement period rather than relying on a single concentration reading. AUC0-t ends at the last measurable concentration, so its interpretation depends on the available sampling period and the concentration measurements collected during it. It is not, by itself, a direct measure of a clinical outcome.

The registry record specifies a mean and standard deviation for this endpoint. It describes sampling around the loading dose and maintenance infusion, including measurements before and after the infusion. The stated schedule includes measurements up to 10 hours after the end of the maintenance infusion, with the maintenance period described as within 24 hours of its start. These time points provide the context for interpreting the concentration profile.

The endpoint is useful for characterizing exposure in a pharmacokinetic study. However, numerical AUC0-t results, group-specific means, standard deviations, and uncertainty estimates are not reported in the registry record. The record therefore identifies what was measured and how the endpoint was defined, but does not establish the observed exposure at any dose level or the precision of those estimates.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: Pharmacokinetic analyses describe drug concentration over time and summarize exposure using measures such as area under a concentration-time curve. In this study, AUC0-t refers to the area from time zero through the last measurable concentration. Because the endpoint is continuous, it can be described using a mean and a measure of dispersion. The registry record specifies the mean and standard deviation, but does not report their numerical values for the primary endpoint.

The concentration measurements were scheduled around the loading dose and maintenance infusion. The registry record lists a measurement no more than 30 minutes before the loading dose, one 5 minutes before the loading dose finished, and further measurements during the maintenance infusion. It also lists measurements before and after the end of that infusion. This schedule is intended to characterize concentration changes across different parts of administration and after infusion ends. The actual concentration values and endpoint summaries are not reported in the registry record.

General: The standard deviation describes how spread out observed measurements are around their mean. It is not the same as the standard error, which describes the uncertainty of an estimated mean. A confidence interval would combine an estimate with an indication of its uncertainty under a specified statistical approach. Numerical standard deviations, standard errors, and confidence intervals for AUC0-t are not reported in the registry record, so the precision of the endpoint estimates cannot be evaluated from the record.

The primary analysis population was the full evaluable population, defined as participants who received study drug infusion for at least 5 hours and had available pharmacokinetic data. This definition makes exposure duration and availability of pharmacokinetic data part of eligibility for the primary pharmacokinetic and pharmacodynamic analyses. The total number in this analysis population is not reported in the registry record. The record does not describe how missing pharmacokinetic measurements were handled or whether any alternative populations were analyzed.

General: An analysis population should be interpreted in relation to the question it is intended to answer. A population defined by treatment receipt and available data can differ from the set of all enrolled participants. When those sets differ, the reasons for exclusion and the handling of missing data help readers assess how representative the analysis may be. Those details are not reported in the registry record.

The study is described as phase II, open-label, multicenter, non-randomized, and single-group, with four escalating dose levels. General: Random allocation is used to reduce systematic differences between groups, while masking can reduce the influence of knowledge of treatment assignment on care or measurement. Neither randomization nor masking is identified for this study. Consequently, comparisons among dose levels should be interpreted as descriptive rather than as randomized comparisons.

The registry record does not report the protocol’s statistical analysis plan, any interim analyses, or a sample-size justification. It also does not report numerical inferential results for the primary endpoint. The record lists 9 outcome measures and no analyses. That information does not identify which methods were used to analyze each outcome, whether analyses were adjusted, or how uncertainty was quantified.

A separate sample-size planning illustration is based on the observed effect, not on the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The record describes these as planning assumptions rather than trial-design details. Numerical planning outputs and the observed effect on which such an illustration would depend are not reported in the registry record. Such illustrations are not observed power and do not show the probability that the completed study detected an effect.

General: Over-dispersion occurs when variability in observed data exceeds what a statistical model assumes. If ignored, uncertainty estimates can be too narrow and inferential conclusions may be misleading. The registry record does not report an over-dispersion assessment or indicate that a particular count or continuous-outcome model was used. No conclusion about model adequacy can therefore be drawn.

General: Multiplicity arises when several outcomes, comparisons, or analyses are considered. The more questions examined, the greater the possibility of a chance finding if each is assessed separately without an appropriate strategy. The registry record identifies 9 outcome measures, but the multiplicity strategy, if any, is not reported in the registry record. This limits interpretation of any isolated inferential result; in this case, numerical primary endpoint results are also not reported.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Dose Level 1", "Dose Level 2", "Dose Level 3", "Dose Level 4")
n   <- c(14, 13, 14, 14)
m   <- c(2681.332, 6460.576, 16992.54, 28531.864)
sp  <- c(2353.3418, 3766.4657, 29927.3911, 17496.3985)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Dose Level 1  14  2681.332  2353.342  1322.553  4040.111
CARM  Dose Level 2  13  6460.576  3766.466  4184.524  8736.628
CARM  Dose Level 3  14  16992.540  29927.391  -287.021  34272.101
CARM  Dose Level 4  14  28531.864  17496.398  18429.744  38633.984

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies 9 outcome measures and lists no analyses. It does not provide a statistical plan describing how those outcomes were prioritized or how multiple comparisons were handled. Whether any multiplicity adjustment was planned or used is not reported in the registry record. Without that information, the implications of examining multiple outcomes cannot be assessed from the registered details.

General: Multiplicity is relevant when researchers evaluate several outcomes or contrasts, because separate statistical tests can increase the chance of at least one chance-positive result. A prespecified hierarchy or adjustment can address that concern, but no such approach is described in the registry record. No p-value for the primary endpoint is reported, so there is no primary-endpoint inferential result to interpret for this study.

The primary pharmacokinetic and pharmacodynamic analysis population was defined as participants who received infusion for at least 5 hours and had available pharmacokinetic data. The registry record does not report the number meeting this definition, how many enrolled participants were excluded from it, or why any were excluded. It also does not describe imputation, censoring, or other handling of missing measurements. These details are not reported in the registry record.

General: Missing data can affect both the number of observations contributing to an estimate and the extent to which that estimate represents the intended population. How much this matters depends on the amount and pattern of missingness and on the analysis methods. Since those details are not reported, the effect of missing data on the endpoint results cannot be evaluated.

The record states that the full evaluable population was the primary population for pharmacokinetic and pharmacodynamic analyses. It does not report other analysis populations or sensitivity analyses. The implications of this population definition therefore cannot be compared with results from an all-enrolled or alternative population.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: convulsion (6.2%).

The registry record reports serious adverse events by dose level. Dose Level 1 lists 1 affected participant among 16 at risk. Dose Level 2 lists 0 among 14, Dose Level 3 lists 0 among 15, and Dose Level 4 lists 0 among 14. These are descriptive counts within the listed groups; they are not estimates from a randomized comparison.

The record also reports other adverse events separately: 11 of 16 participants at Dose Level 1, 12 of 14 at Dose Level 2, 10 of 15 at Dose Level 3, and 13 of 14 at Dose Level 4. These counts should not be combined with the serious-event counts. The registry record lists Convulsion at 6.2% among the top serious terms. The number of events associated with that term is not reported in the registry record.

Death counts are not reported in the registry record. A null death field should not be interpreted as a reported zero. The record does not provide additional context about event timing, duration, relatedness to study treatment, or participant-level overlap among event categories.

General: Adverse-event counts describe events recorded in a study and do not by themselves establish that an event was caused by treatment. Comparisons across groups can also be difficult to interpret when assignment is non-randomized and group sizes differ. The listed figures therefore describe what was recorded by dose level; they do not establish comparative safety or a causal relationship.

13. What the Result Does, and Does Not, Mean

The registry record establishes that a phase II, open-label, non-randomized, single-group study evaluated dexmedetomidine in intubated and mechanically ventilated pediatric subjects across four dose levels. It identifies AUC0-t as the primary pharmacokinetic endpoint and describes the population and sampling schedule. These details clarify the study’s purpose and the kind of measurement it sought to characterize.

The record does not report numerical results for the primary endpoint. It therefore does not show the observed average AUC0-t, the amount of variation, the precision of an estimate, or how exposure differed across dose levels. No inference about the direction or magnitude of an exposure pattern can be drawn from the endpoint definition alone. Lack of a reported estimate is not evidence that there was no difference or no effect.

The design also limits what can be claimed. There was no randomized control group identified, and the dose-level groups should not be treated as a like-for-like comparison. Descriptive differences among groups, even if numerical results were available, would not alone establish that dose caused those differences. The registry record does not report adjusted comparisons or a control-based estimate.

The adverse-event entries provide descriptive counts for serious and other adverse events by dose level and identify Convulsion at 6.2% among the top serious terms. They do not establish causation or a comparative safety profile. Death counts and further event details are not reported in the registry record.

General: Statistical conclusions depend on both the observed estimates and their uncertainty, as well as on the design and analysis assumptions. Here, the available registered details support an account of the study’s structure and endpoint, but not a judgment about the size or precision of the primary pharmacokinetic findings. The trial’s statistical meaning is consequently bounded by the information reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for the kind of question it was designed to address: characterizing pharmacokinetic and pharmacodynamic profiles across escalating dose levels in pediatric subjects. A concentration-time endpoint such as AUC0-t summarizes exposure over a measurement period and differs from a clinical outcome that directly describes a participant’s health state. Keeping that distinction clear helps prevent exposure measurements from being mistaken for evidence about clinical benefit.

The study’s population definition is also important. The primary analysis population required at least 5 hours of infusion and available pharmacokinetic data. That defines whose measurements were intended to inform the primary analyses, while leaving the number meeting the criteria unreported. The difference between enrolled participants and an evaluable analysis population can matter when interpreting how broadly results apply.

The non-randomized, open-label design illustrates why study design constrains statistical interpretation. Dose-level observations can contribute to characterization, but the groups do not provide a randomized control contrast. A reader should distinguish describing measurements across dose levels from estimating a causal treatment effect.

The registry record also demonstrates the difference between an endpoint definition and a reported result. It gives a detailed primary endpoint and sampling schedule, but numerical endpoint estimates are not reported. A clearly defined measure does not by itself convey its observed value or precision.

Finally, the adverse-event counts are descriptive and should be read separately from the pharmacokinetic endpoint. They do not establish causality or comparative risk. These distinctions—between exposure and clinical outcomes, enrolled and evaluable populations, and description and causal comparison—are central to reading this study statistically.

15. 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 primary limitation for interpreting efficacy-related or pharmacokinetic findings is that numerical AUC0-t results are not reported in the registry record. Group-specific estimates, variability, and uncertainty are also not reported. The endpoint and schedule can be described, but the magnitude and precision of the measured exposure cannot be assessed.

The non-randomized, open-label, single-group design does not provide a randomized control comparison. Dose-level groups therefore cannot be assumed to be exchangeable, and differences among them would not by themselves establish causal effects of dose. The registry record does not report adjusted comparisons or details that would permit evaluation of group comparability.

The primary analysis population required at least 5 hours of infusion and available pharmacokinetic data. The size of this population, the number excluded, and reasons for exclusion are not reported in the registry record. The handling of missing data and any sensitivity analyses are also not reported. These omissions limit assessment of how selection into the analysis population might affect interpretation.

The record identifies 9 outcome measures, but a multiplicity strategy is not reported. The statistical analysis plan, interim analyses, sample-size justification, and model details are not reported in the registry record. These absences prevent evaluation of prespecification, analytical assumptions, and the basis for planned precision.

Safety reporting is likewise limited: death counts and event-level details such as timing and treatment relatedness are not reported in the registry record. The available adverse-event counts are descriptive and do not provide a randomized comparative safety estimate. These limitations concern what can be concluded from the registry record; they do not establish that unreported analyses or information were absent from other study materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Pediatrics Subjects — NCT00652028.
• Registry record last updated 2017-04-13; status last verified 2015-08.
• Results first posted 2015-08-14.
• 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.

19. Record Summary

This completed phase II study enrolled 69 intubated and mechanically ventilated pediatric subjects and evaluated dexmedetomidine through an intravenous loading dose followed by continuous infusion. It was open-label, multicenter, non-randomized, and described as a single-group escalating-dose study with four dose levels.

The primary endpoint was AUC0-t, measured in picograms*hr/mL. The primary analysis population included participants who received infusion for at least 5 hours and had available pharmacokinetic data. Numerical primary endpoint results and the size of that analysis population are not reported in the registry record.

Serious and other adverse-event counts are listed by dose level. The registry record identifies Convulsion at 6.2% among the top serious terms; death counts are not reported. The record does not describe a randomized control comparison, the multiplicity strategy, missing-data handling, or the statistical analysis plan.