A Study of MK-0869 (Aprepitant) and MK-0517 (Fosaprepitant) in Pediatric Participants Receiving Chemotherapy (MK-0869-134): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of MK-0869 (Aprepitant) and MK-0517 (Fosaprepitant) in Pediatric Participants Receiving Chemotherapy (MK-0869-134) (NCT00818259), a non-randomized phase 1 study. The primary outcome is Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant.

2. Clinical Question

3. Trial Design

This was a Phase 1, multicenter, open-label study with non-randomized allocation and a single-group model. The registry lists enrollment of 92 and records the study as terminated. The listed start date is 2009-02-05, and the primary completion date is 2014-01-20. The reason for termination is not reported in the registry record.

The study had five parts, with regimens and age ranges varying across parts. Parts IA and IB studied fosaprepitant in participants from 12 to 17 years of age, with different dosing arrangements; Part IA included aprepitant on subsequent days. Parts IIA and IIB studied age-specific oral aprepitant regimens. Part III involved ondansetron for participants from birth to <12 years of age, with dexamethasone optional except in the birth-to-one-year cohort. Part IV studied an age-specific aprepitant regimen, while Part V studied intravenous fosaprepitant in participants from 6 months to <12 years of age. The registry record does not provide complete descriptions of every regimen in the posted arm descriptions.

Ondansetron and, in some groups, dexamethasone were co-administered alongside the study regimens. The design therefore reflects treatment regimens in the context of chemotherapy and local standard of care, not an isolated test of aprepitant or fosaprepitant against a randomized control. No masking was used, and allocation was not randomized. Comparisons across parts can be affected by differences in age, regimen, and other features of the study groups. The registry record does not report a statistical plan that would establish adjusted comparisons across those parts.

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: Of the 92 unique participants who were enrolled and randomized in Parts I (n=23), II (n=39), III (n=19), IV (n=5) and V (n=6), 91 took part in this study. One participant randomized in Part IIB was discontinued prior to treatment.

Only the first 6 of 9 groups are shown.

Randomization

Part I

Reasons for not completing this period:

Part II

Reasons for not completing this period:

Part III

Analysis population for the primary outcome, as defined in the registry: The population consisted of all participants who received at least one dose of fosaprepitant and/or aprepitant and were evaluable for this PK parameter. No PK assessements were performed on the Part III-ondansetron group; this group received no aprepitant.

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: For analysis purposes, baseline (BL) data are presented by study part groups. The BL analysis population includes all unique enrolled participants in Parts I, II, III, IV and V. Part III participants who entered Parts IV and V are only counted in Part III; Part IV participants who entered Part V are only counted in Part IV.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant, measured over Up to 24 hours post fosaprepitant/aprepitant dose.

The primary endpoint was area under the time-concentration curve from 0 to 24 hours for aprepitant, reported in hr*ng/mL. The registry describes this as a measure of the amount of aprepitant in plasma. Fosaprepitant is a prodrug that is rapidly converted to aprepitant after intravenous administration, so the endpoint is relevant to both oral aprepitant dosing and fosaprepitant dosing.

Pharmacokinetic measurements describe drug exposure over time rather than a clinical outcome such as nausea or vomiting. The registry specifies the mean as the summary measure and the standard deviation as the measure of dispersion. Blood sampling times differed across study parts and followed the dosing or chemotherapy schedule described for each part. This matters when interpreting exposure estimates: they arise from the specific regimen and sampling schedule, and should not be treated as a direct measure of symptom prevention.

The endpoint’s numerical results, including means and standard deviations by study part, are not reported in the registry record. Accordingly, the posted information does not allow an assessment of the observed exposure levels, variation among participants, or precision of the estimated means. No confidence interval or inferential analysis for this endpoint is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint summarize?

AUC, or area under the concentration-time curve, summarizes plasma drug concentration across a defined time interval. In this study the interval was 0 to 24 hours, and the endpoint was aprepitant AUC in hr*ng/mL. As a general statistical concept, this kind of measure condenses a series of concentration measurements into an overall exposure summary. It does not describe a clinical symptom directly.

The registry specifies that the endpoint is summarized by a mean and standard deviation. A mean describes the average value in the assessed group; a standard deviation describes the spread of individual values around that mean. The standard deviation is not the same as a confidence interval: it describes variation among observations, whereas a confidence interval describes uncertainty in an estimate. Numerical means and standard deviations are not reported in the registry record, and confidence intervals are not reported in the registry record.

Why does the sampling schedule matter?

Blood samples were scheduled at different times across study parts. Some schedules were anchored to fosaprepitant dosing, some to aprepitant dosing, and some to the start of chemotherapy. In general, pharmacokinetic estimates depend on the timing of measurements because those observations characterize the concentration-time profile. The posted record describes the sampling schedules, but does not report numerical AUC results or details of how missing concentration measurements, if any, were handled.

Fosaprepitant is described as a prodrug that is rapidly converted to aprepitant after intravenous administration. Therefore, AUC for aprepitant is relevant to assessment of exposure following either fosaprepitant or aprepitant administration. That shared endpoint does not make the regimens interchangeable for interpretation: the drug, route, age group, and sampling schedule can differ among parts.

What does the study structure permit?

Non-randomized allocation means participants were not assigned to regimens by randomization, and the study was open-label. In general, randomization helps balance both measured and unmeasured characteristics across comparison groups, while masking can reduce some influences of treatment knowledge on assessment. Without these design features, differences between groups may reflect participant or treatment-context differences as well as the regimen. Here the parts covered different age ranges and dosing approaches, and the record identifies the arms as not being a like-for-like control comparison.

The study is described as single-group overall, while the registry lists multiple study parts and intervention groups. This description does not support treating the listed parts as parallel randomized arms. Part III received ondansetron and no aprepitant, and no pharmacokinetic assessments were performed for that group. Thus it does not contribute aprepitant AUC data under the stated primary population definition.

How should uncertainty be understood?

In general, an estimate is more informative when its uncertainty is reported alongside its central value. A standard deviation describes participant-level variability, while a confidence interval can communicate uncertainty around an estimated mean or difference. The registry record reports the intended summary format for the primary endpoint, but not its values or interval estimates. There is therefore no basis for judging how precise an AUC estimate was, or for deciding whether apparent differences among parts could be distinguished from sampling variability.

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such illustrations are planning calculations, not observed power and not evidence that the study had a particular probability of detecting an effect. The effect to detect is expressed as a stated fraction of the observed effect in those calculations. The registry record does not report the trial’s own sample-size justification, and the stated illustration should not be mistaken for the study’s design rationale.

Why is over-dispersion relevant in general?

For count outcomes, a statistical model may assume a particular relationship between the average count and its variability. Over-dispersion means the observed variability is greater than that assumption allows; if ignored, standard errors can be too small and intervals or tests can look more conclusive than warranted. This is a general consideration for count data, not a reported feature of this study. The registry record does not report a model for count outcomes or an analysis of over-dispersion.

For the continuous AUC endpoint, the registry’s stated mean and standard deviation are descriptive summaries. No distributional assessment, transformation, adjusted model, or inferential procedure for this endpoint is reported in the registry record. General statistical methods cannot substitute for those missing analysis details or for the absent numerical results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures and zero analyses. It does not report a multiplicity strategy for handling several outcomes, study parts, age ranges, or regimen comparisons. In general, when many outcomes or comparisons are examined, the chance of an apparently notable result arising by chance can increase. A prespecified strategy can clarify which findings are primary and how secondary or exploratory analyses are interpreted. Such a strategy is not reported in the registry record.

The primary outcome description defines the pharmacokinetic population as participants who received at least one dose of fosaprepitant and/or aprepitant and were evaluable for the parameter. The number evaluable is not reported in the registry record. The record also states that Part III received no aprepitant and had no pharmacokinetic assessments. It does not report further analysis-population counts or the handling of missing pharmacokinetic measurements.

Missing-data handling can affect estimates when measurements are unavailable, particularly if missingness is related to participant characteristics or observed outcomes. This is a general consideration, not a claim that missing data occurred in this study. The registry record does not report the extent or reasons for missing endpoint data, any imputation method, or sensitivity analyses.

The record does not report an analysis plan, interim analyses, or a multiplicity adjustment. It is therefore not possible to determine from the posted results which analyses were planned in advance, how any multiple comparisons were addressed, or whether the reported outcomes reflect a complete analysis set. The absence of those details should be distinguished from evidence that a particular method was or was not used.

11. 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: febrile neutropenia (21.1%), neutropenia (10.5%), vomiting (10.5%), enterobacter bacteraemia (9.1%), thrombocytopenia (8.3%).

The registry lists serious adverse-event counts and other adverse-event counts for each study group. For serious adverse events, the reported affected counts are 4 of 12 in Part IA, 1 of 11 in Part IB, 7 of 19 in Part IIA, 4 of 19 in Part IIB, 5 of 19 in Part III, 2 of 20 in Part IV, and 9 of 23 in Part V. For other adverse events, the corresponding affected counts are 11 of 12, 5 of 11, 18 of 19, 15 of 19, 15 of 19, 13 of 20, and 16 of 23. These are descriptive counts within each listed group.

The groups differ in age ranges and regimens, and allocation was non-randomized. The counts therefore should not be treated as a controlled comparison or as evidence that one regimen caused more events than another. The registry lists serious-event terms and percentages: febrile neutropenia, 21.1%; neutropenia, 10.5%; vomiting, 10.5%; Enterobacter bacteraemia, 9.1%; thrombocytopenia, 8.3%; and septic shock, 8.3%. The registry record does not report enough detail to interpret these percentages as a comparison between groups. Death counts are not reported in the registry record.

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

The study record documents a pediatric investigation of aprepitant and fosaprepitant in the setting of emetogenic chemotherapy. Its primary endpoint was pharmacokinetic: aprepitant exposure over 0 to 24 hours. The record defines the endpoint and the intended summary statistics, but does not report numerical AUC values. As a result, it does not show the observed exposure levels or their variability, and it does not allow a reader to assess the precision of those estimates.

The study also records adverse events in its various parts. These counts describe events among participants listed in each group, but the non-randomized, open-label design and differing regimens limit comparisons between groups. The adverse-event listings do not establish that a study drug caused a particular event, nor do they provide a randomized estimate of comparative safety.

The registry record does not report a numerical clinical outcome showing whether nausea or vomiting was prevented. The primary endpoint is a drug-exposure measure, not a direct clinical measure of symptom prevention. No treatment-effect estimate for a clinical outcome is reported in the registry record. The posted information therefore cannot establish the magnitude or precision of a clinical benefit or harm, and it should not be read as a conclusion that a treatment works or does not work.

In general, a study’s design, outcome definitions, analysis methods, and numerical results all contribute to interpretation. Here, the record provides design and endpoint descriptions, but lacks numerical primary endpoint results and reports zero analyses. Its useful contribution in the posted form is to describe the study’s structure and recorded safety summaries, while leaving the principal pharmacokinetic findings unavailable.

13. Why This Trial Matters Statistically

This study is statistically notable for spanning a wide pediatric age range and evaluating age-specific dosing approaches for aprepitant and fosaprepitant. Pharmacokinetic assessment is relevant to describing drug exposure when dosing regimens differ by age and route. The registry identifies AUC from 0 to 24 hours as the primary measure and describes the sampling schedules used across study parts.

The design also illustrates why comparison language matters. A study can list several treatment groups without being a randomized, parallel-group comparison. Here, allocation was non-randomized, masking was absent, and the registry describes a single-group model. Different parts used different ages, doses, and combinations with ondansetron and dexamethasone. Descriptive group results should not be interpreted as if random assignment had made the groups comparable.

The record also shows the distinction between defining an endpoint and reporting its result. It specifies what AUC measures and how it was intended to be summarized, but numerical means and standard deviations are not reported. Without those values and an analysis, readers cannot evaluate exposure estimates or their precision. This is a central limitation for interpreting a pharmacokinetic study.

Finally, adverse-event counts can be informative as descriptive safety reporting, while still being insufficient for causal comparisons. Their interpretation depends on who was included, how events were collected, and the treatment context. The posted record gives counts and selected event percentages but does not provide a randomized basis for comparing regimens. The statistical lesson is to separate what a registry documents from what its design and results can support.

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 primary limitation is the absence of numerical results for the primary pharmacokinetic endpoint. The registry record defines AUC from 0 to 24 hours and specifies mean and standard deviation summaries, but does not report those estimates. It also reports zero analyses. Consequently, the posted record does not support an assessment of effect magnitude, variability, or precision for the main endpoint.

The design limits comparative conclusions. Participants were not randomized, the study was open-label, and the listed groups differed in age range and regimen. Several parts included ondansetron and some included dexamethasone; the record also states that Part III received no aprepitant and had no pharmacokinetic assessments. These groups are not a like-for-like control comparison.

The registry lists enrollment of 92, but the number evaluable for the primary endpoint is not reported in the registry record. The record does not report the extent or handling of missing pharmacokinetic data, the reason for termination, or a statistical analysis plan. It also does not report the study’s sample-size justification, interim analyses, or a multiplicity strategy. The sample-size assumptions described for planning illustrations should not be interpreted as the trial’s own design rationale or as observed power.

Safety information is descriptive and does not establish causation. The registry’s serious-event percentages do not, by themselves, enable like-for-like risk comparisons across the different parts. Death counts are not reported in the registry record. These gaps constrain interpretation of both the endpoint results and the comparative safety profile.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of MK-0869 (Aprepitant) and MK-0517 (Fosaprepitant) in Pediatric Participants Receiving Chemotherapy (MK-0869-134) — NCT00818259.
• Registry record last updated 2018-09-25; status last verified 2018-08.
• Results first posted 2014-11-18.
• 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.

18. Record Summary

The registry record describes NCT00818259, a Phase 1, multicenter, open-label, non-randomized study of aprepitant and fosaprepitant in pediatric participants receiving emetogenic chemotherapy. It lists enrollment of 92 and records the study as terminated. The primary endpoint was aprepitant AUC from 0 to 24 hours, summarized as a mean with standard deviation. Numerical results for that endpoint are not reported in the registry record, and the record lists zero analyses.

Study parts evaluated different age-specific regimens, with ondansetron and sometimes dexamethasone also used. The registry reports adverse-event counts and selected serious-event terms, but the non-randomized design does not support treating the groups as a like-for-like comparison. The reason for termination and death counts are not reported in the registry record.