Open-Label Safety and Tolerability Study of Oxymorphone for Acute Postoperative Pain in Pediatric Subjects.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label Safety and Tolerability Study of Oxymorphone for Acute Postoperative Pain in Pediatric Subjects. (NCT00801398), a na phase 3 study. The primary outcome is Summary of Visual Analog Scales (VAS) of Pain Intensity Change From Baseline by Treatment Group With Single Dose of Oxymorphone IR Tablet and Multiple Dose of Oxymorphone IR Tablet.

2. Clinical Question

The study was intended to evaluate safety, pharmacokinetics, and effectiveness in pediatric subjects with acute postoperative pain. Its brief summary describes oral study medication beginning after parenteral analgesia is discontinued and after pain reaches a moderate level, defined as a VAS score greater than or equal to 40. That summary describes the context for dosing; it does not supply numerical evidence about pain changes after treatment.

Because the study was open-label and single-group, its results cannot directly separate changes associated with study medication from changes over time, other care, or expectations. The registry record does not report a randomized comparison, a blinded assessment, or an adjusted estimate that would address those issues. The primary question is therefore descriptive: what pain-intensity changes and safety observations were recorded during the oxymorphone dosing periods? The numerical primary-outcome answer is not reported in the registry record.

3. Trial Design

This completed Phase 3 study is described as an open-label, ascending, two-part evaluation of single and multiple doses of oxymorphone for acute postoperative pain in pediatric subjects. The registry record lists a single group, allocation as NA, and masking as NONE. Enrollment is 58. The recorded study start is 2009-02-17 and primary completion is 2011-04-18.

The intervention is Oxymorphone IR. The arm description calls it an open-label, two-part ascending-dose multicenter study. The adverse-event groups identify single-dose and multiple-dose cohorts at 5mg, 10mg, and 15mg tablet strengths. Those cohorts describe dose experience, not randomized treatment arms with a concurrent control. The registry record does not report how subjects entered the dose groups, whether dose escalation depended on prespecified criteria, or the numbers assigned to each part beyond the group-specific safety counts.

The primary outcome is a summary of VAS pain-intensity change from baseline by treatment group, with the measure expressed in mm and summarized as a mean with standard deviation. The listed single-dose assessment times are 15min, 30min, 1h, 2h, 3h, 4h, 6h, or Rescue. The multiple-dose timeframe includes those times, subsequent doses every 4-6 hours (Multiple Dose #1-11), and Early Termination. The outcome description specifies change from baseline in the multiple-dose setting, while the title names both single-dose and multiple-dose tablets.

The record lists pharmacokinetic secondary outcomes for single-dose AUC(0-t), AUC(0-inf), Cmax, Tmax, terminal rate constant, and terminal half-life. Numerical outcome results for these measures are not reported in the registry record. The record also states that the study was required by the FDA and notes that Endo Pharmaceuticals Inc. No longer promotes opioids and no longer markets Opana® ER. That statement does not provide additional design or outcome details.

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

Analysis population for the primary outcome, as defined in the registry: ITT Population

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: ITT Population; Single Dose Total = 33; Multiple Dose Total = 25;

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Summary of Visual Analog Scales (VAS) of Pain Intensity Change From Baseline by Treatment Group With Single Dose of Oxymorphone IR Tablet and Multiple Dose of Oxymorphone IR Tablet, measured over Single Dose Timeframe: 15min, 30min, 1h, 2h, 3h, 4h, 6h or Rescue; Multiple Dose Timeframe: 15min, 30min, 1h, 2h, 3h, 4h, 6h, subsequent doses every 4-6 hours (Multiple Dose #1-11), and Early Termination.

The primary outcome measures change from baseline in pain intensity using a 100-mm Visual Analog Scale. A VAS is a continuous measure: the reported value represents a position on a scale, and a change score describes how that value differs from the participant’s baseline assessment. The registry identifies the unit as mm and the summary parameter as a mean with standard deviation. In general, a mean describes the average change in a group, while the standard deviation describes the spread of individual changes around that average.

Repeated assessment is relevant because pain can vary during the postoperative period and across dosing intervals. The record lists assessments at 15min, 30min, 1h, 2h, 3h, 4h, 6h, or Rescue for the single-dose timeframe, and includes subsequent doses every 4-6 hours (Multiple Dose #1-11) and Early Termination for the multiple-dose timeframe. These time points can describe the course of measured pain over treatment, but the registry record does not give the results at any of them.

The registry identifies the primary-outcome population as the ITT Population. It does not report the numerical mean changes, standard deviations, participant counts at each time point, confidence intervals, or a test of change. It therefore does not establish the size or precision of any observed pain-intensity change. The endpoint is useful for describing reported pain trajectories, but without a control group it cannot by itself establish that a change was caused by the study medication.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary endpoint as a continuous measure: change from baseline in pain intensity on a 100-mm VAS. It names the mean as the summary parameter and standard deviation as the measure of dispersion. In general, the mean is the arithmetic average of observed values, and the standard deviation describes how much individual values vary around that average. Neither statistic alone gives the full distribution of pain changes, and the record does not report the numerical values needed to examine that distribution.

What does change from baseline describe?

A change score compares an observation after treatment begins with a baseline observation for the same participant. The group mean change summarizes the average direction and size of those within-participant changes. In general, a positive or negative sign depends on how the scale and change are defined. The registry record does not state the sign convention or provide actual change values, so no direction or magnitude can be inferred from the endpoint label alone.

The registry lists assessment times across single-dose and multiple-dose periods. Repeated measurements allow a study to describe the course of an outcome over time. However, repeated measurements from the same participant are related rather than independent. Statistical analyses generally need to account for that within-participant relationship if they estimate an overall trajectory or compare time points. The registry record does not report the model, covariance structure, or other method used to analyze repeated VAS measurements.

What would uncertainty measures add?

In general, a confidence interval gives a range of values compatible with the data and analysis under the method’s assumptions. Its width conveys precision: wider intervals indicate less precise estimates, while narrower intervals indicate more precise estimates. A confidence interval for a mean change would help readers distinguish the point estimate from its uncertainty. The registry record does not report confidence intervals for the primary outcome. It also does not report p-values or a stated hypothesis test for that endpoint.

Standard deviation and standard error serve different purposes. In general, standard deviation describes variation among participant measurements, while standard error describes uncertainty in an estimated mean. The registry specifies standard deviation for the primary outcome; it does not report standard errors. Without the numerical mean, standard deviation, and analysis population at each time point, the precision of the estimated mean cannot be assessed from the registry description.

Why does the design matter for analysis?

A single-group study can describe measurements before and after dosing, but it has no randomized control group for estimating what would have happened without the study intervention. This is a general design limitation, not a statistical correction that can be resolved simply by calculating a p-value. The study is also open-label. In general, knowledge of treatment can influence reporting or assessment of a subjective outcome such as pain. The record does not describe blinded outcome assessment or an adjustment intended to address this concern.

The different dose groups are not a like-for-like control comparison. They represent dose experience in an ascending-dose study, and the record does not report random assignment among them. Differences between dose groups could reflect factors other than dose, including the way participants entered the cohorts. The registry record does not provide a comparative analysis or adjustment strategy that would support interpreting dose-group differences as causal.

The sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. The record does not report the underlying observed effect or the resulting planning values. Such calculations are hypothetical planning illustrations, not observed power and not evidence about the study’s ability to detect an effect. They also do not turn this single-group study into a two-arm comparison.

What statistical information is absent?

The registry record lists no analyses, and numerical primary endpoint estimates are not reported. It does not report a statistical analysis plan, model specifications, adjustment variables, handling of repeated measurements, missing-data methods, or interim analyses. The record also does not report the sample-size justification used to design the study. When these details are absent, readers cannot determine which analysis choices were prespecified or assess how sensitive the conclusions might be to alternative assumptions.

In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. For continuous pain scores, analysts may examine whether the chosen model adequately reflects the outcome distribution and the repeated observations. The registry record does not describe an over-dispersion assessment, and no such conclusion can be drawn from the available information. More broadly, statistical concepts explain what an analysis could address; they do not supply missing estimates or establish results that the registry record does not report.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome covers multiple scheduled assessments and both single-dose and multiple-dose periods. The secondary outcomes include six single-dose pharmacokinetic measures. When analyses examine multiple outcomes, dose groups, or time points, the chance of at least one apparently unusual result can increase. In general, a multiplicity strategy may define a primary comparison, adjust inference, or clearly distinguish confirmatory from exploratory analyses. The registry record does not report a multiplicity plan, a testing hierarchy, or adjusted results.

The record lists 8 outcome measures and 0 analyses. It does not report which time points, if any, were designated for formal hypothesis testing, nor whether the primary outcome was evaluated as a single summary or across repeated time points. No interim analyses or stopping rules are reported in the registry record. Their absence from the record is not evidence that a particular procedure was or was not used; the details are not reported in the registry record.

The primary-outcome population is named as the ITT Population, but the registry record does not give the number of participants included in that analysis or explain how the population was defined. It does not report participant counts available at each assessment, reasons for missing measurements, or the method used to handle missing data. This matters generally because repeated pain assessments may be unavailable for different reasons, and conclusions can depend on how missing observations are treated.

The record also does not report whether safety analyses used all treated participants or another defined population. The group-specific counts identify participants at risk for serious and other adverse events, but do not describe the analysis rules or follow-up completeness. Without those details, readers should distinguish the reported counts from a complete account of missingness or analysis-population definitions.

11. Safety Results

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

Deaths

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: somatosensory evoked (12.5%), monoplegia (12.5%), spinal cord oedema (12.5%), atelectasis (11.1%), fat embolism (11.1%).

The registry lists serious adverse events and other adverse events separately for six Oxymorphone IR dose groups. The groups comprise single-dose and multiple-dose cohorts at 5mg, 10mg, and 15mg. For each group, the record gives the number at risk and the number affected; it lists zero deaths in every group. These are counts within the named cohorts, not randomized comparisons against a control group.

For the single-dose groups, serious adverse events are listed as 0 of 13 at 5mg, 1 of 9 at 10mg, and 1 of 11 at 15mg. Other adverse events are listed as 3 of 13, 4 of 9, and 7 of 11, respectively. For the multiple-dose groups, serious adverse events are listed as 1 of 9 at 5mg, 1 of 8 at 10mg, and 0 of 8 at 15mg. Other adverse events are listed as 8 of 9, 5 of 8, and 6 of 8, respectively.

The registry also lists serious-event terms and percentages, including Somatosensory evoked and Monoplegia at 12.5%, Spinal cord oedema at 12.5%, and Atelectasis, Fat embolism, and Pupils unequal at 11.1%. The record does not give the denominator or further context for these term percentages. Counts and listed terms describe what the registry records; without a control group and fuller event context, they do not establish whether an event was caused by treatment or permit a comparative risk estimate.

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

The registry record identifies a pediatric postoperative-pain study of immediate-release oxymorphone and describes the outcome and safety measures collected. It establishes that the primary endpoint was VAS pain-intensity change from baseline, with a mean and standard deviation, and that the study included single-dose and multiple-dose periods. It also reports group-specific adverse-event counts and lists single-dose pharmacokinetic outcomes.

It does not report numerical results for the primary endpoint. Therefore, the size and direction of the average pain change, variation among participants, and precision of the estimate cannot be assessed from the registry record. The numerical pharmacokinetic outcomes are also not reported in the registry record. A measure being named as an outcome does not, by itself, show what values were observed or what conclusions were drawn.

The design is open-label and single-group, with no randomized control comparison. In general, observed changes in an uncontrolled study cannot distinguish effects associated with treatment from other changes over time or differences in care. The record does not report an analysis that resolves this limitation. Comparisons across the dose cohorts should likewise not be read as randomized dose comparisons.

The safety counts give a descriptive account for the listed groups, including the number at risk, the number affected, and deaths. They do not provide a comparative estimate against an untreated or active control group. The listed serious-event terms and percentages also lack denominator details in the registry record, limiting their interpretation.

These limitations do not erase the descriptive information the record contains. Rather, they define what can be concluded from it: the study’s design, measures, dosing cohorts, and some safety counts are identifiable, while numerical primary-outcome results and key analysis details are not. No conclusion about treatment effectiveness or comparative safety can be drawn from the posted results described in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why the design and the reported results must be read together. A continuous pain measure can produce detailed descriptions of change across repeated assessments, but those measurements do not automatically provide a causal estimate. Here, the registry identifies an open-label, single-group study and gives no randomized control comparison. That distinction is essential when interpreting any before-and-after change in a subjective outcome.

The record also demonstrates the difference between naming an endpoint and reporting its results. It specifies the VAS measure, unit, summary statistic, population, and assessment schedule, but does not report the numerical primary-outcome estimates. Without those values, readers cannot assess magnitude, variability, or precision. Outcome definitions support interpretation of reported estimates; they cannot substitute for estimates that are not reported in the registry record.

The safety information provides a separate example of descriptive evidence. Counts by dose cohort can show what the registry records in those groups, but without a randomized comparator they do not isolate differences attributable to dose or treatment. The group structure and differing numbers at risk should remain visible in any interpretation rather than being treated as though the cohorts were exchangeable control arms.

Finally, the record names multiple pain assessment times and pharmacokinetic measures, while not describing multiplicity handling, missing-data methods, or analysis specifications. These gaps matter because methods affect how repeated observations and multiple outcomes are interpreted. Statistical transparency requires both a clear design and enough results and analysis detail to evaluate uncertainty. This record offers some design and safety details, but does not report the primary numerical results needed to judge the pain endpoint.

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.

Several limitations are specific to the information reported for this study. First, the study is open-label and single-group, with allocation listed as NA and masking as NONE. There is no randomized control arm in the record. Consequently, observed pain changes cannot be separated from the natural postoperative course, other care, or expectations using a controlled comparison.

Second, the registry record does not report numerical results for the primary endpoint. Although it identifies a mean, standard deviation, ITT Population, and assessment schedule, it gives no mean changes or corresponding variability. It also does not report confidence intervals, p-values, or participant counts contributing to each assessment. This prevents evaluation of the magnitude and precision of the primary outcome.

Third, the description does not explain the analysis of repeated measurements or the handling of missing observations. It does not report details of the ITT definition, participant flow, missingness by time point, or sensitivity analyses. The record also does not report a statistical analysis plan, multiplicity methods, interim analyses, or the trial’s sample-size justification.

Fourth, the ascending-dose cohorts should not be interpreted as randomized dose comparisons. The record does not report how subjects entered each cohort or provide an adjusted comparison across dose groups. Numerical results for the listed pharmacokinetic secondary outcomes are not reported in the registry record. The safety counts are descriptive, and the context and denominator for the listed serious-event term percentages are not reported in the registry record.

These limitations concern both the study design and the completeness of the registry results. They restrict causal interpretation and prevent a numerical assessment of the primary endpoint from the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open-Label Safety and Tolerability Study of Oxymorphone for Acute Postoperative Pain in Pediatric Subjects. — NCT00801398.
• Registry record last updated 2019-02-27; status last verified 2018-12.
• Results first posted 2019-02-27.
• 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

NCT00801398 is a completed Phase 3, open-label, two-part ascending-dose study of Oxymorphone IR for acute postoperative pain in pediatric subjects. The registry lists enrollment as 58, a single-group model, allocation as NA, and masking as NONE. The primary outcome is change from baseline in 100-mm VAS pain intensity, summarized by mean and standard deviation in the ITT Population, across single-dose and multiple-dose timeframes.

The record lists six single-dose pharmacokinetic secondary outcomes and gives adverse-event counts for six dose cohorts: 5mg, 10mg, and 15mg in each dosing period. No deaths are listed in those groups. Numerical primary-outcome and pharmacokinetic results are not reported in the registry record. The record also does not report detailed analysis methods, missing-data handling, or multiplicity procedures. Because there is no randomized control group, the study’s observations do not provide a controlled treatment comparison.