Open-Label Safety and Tolerability of Oxymorphone IR and ER in Opioid Tolerant Pediatric Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label Safety and Tolerability of Oxymorphone IR and ER in Opioid Tolerant Pediatric Subjects (NCT00765856), a na phase 3 study. The primary outcome is Extent of Exposure to Oxymorphone Extended-Release: Average Daily Dose.

2. Clinical Question

The registry describes a treatment sequence rather than a test of oxymorphone against another treatment. Participants were to convert from their current opioid, undergo titration, and then enter a maintenance period on a fixed dose established during titration. The summary says titration was intended to end when the fixed dose was tolerated and adequate analgesia was achieved; this describes the study’s stated process, not a reported finding about participants’ pain outcomes.

The primary endpoint addresses drug exposure, not comparative pain relief or a causal treatment effect. The four secondary outcomes also concern exposure to extended-release or immediate-release oxymorphone. The registry record does not report a separate control group, a placebo comparison, or a randomized treatment contrast. Accordingly, the central statistical question is descriptive: what doses were recorded among participants in each treatment period? The primary endpoint’s observed mean and standard deviation are not reported in the registry record.

3. Trial Design

This was a Phase 3, open-label, single-group study of extended-release oxymorphone in opioid-tolerant pediatric subjects with chronic pain. The registry lists allocation as NA and masking as none. Enrollment was 27. The study started on 2008-11-17, and primary completion was recorded as 2010-02-22. Its status is terminated.

The study summary describes conversion from participants’ current opioid to extended-release oxymorphone, followed by titration. During titration, extended-release tablets were taken every 12 hours, with dose adjustments based on review of pain scores. Immediate-release oxymorphone 5 mg was described as medication for breakthrough pain, used as needed. After participants reached a fixed dose considered tolerable with adequate analgesia, they were to proceed to an open-label 3-month maintenance period on that dose. These are descriptions of the planned treatment process; they do not establish how many participants reached any particular dose or pain outcome.

The primary endpoint timeframe is Day 1 up to Day 112, described as approximately 4 weeks for titration and 12 weeks for maintenance. The registry notes that all participants entering maintenance finished titration. The primary endpoint population is described as participants enrolled in each treatment period, while the safety population includes all participants who took at least 1 dose.

The sponsor terminated the study early because of a change in the FDA postmarketing requirement. The endpoint description explicitly says the study was not terminated for safety reasons. This context matters when interpreting the shorter-than-planned exposure that may result from early termination, but the registry does not report individual follow-up duration or the extent to which early termination affected endpoint availability.

Because there was one treatment group and no masking, the design can describe treatment exposure and reported safety events but cannot provide a like-for-like randomized comparison. The registry record does not report a statistical analysis plan or a sample-size justification.

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.

Titration Period

Maintenance Period

Analysis population for the primary outcome, as defined in the registry: Safety population defined as all participants that took at least 1 dose of study medication.

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

6. Primary Endpoint

The registry lists the primary outcome as Extent of Exposure to Oxymorphone Extended-Release: Average Daily Dose, measured over Day 1 up to Day 112 (approximately 4 weeks for titration period and 12 weeks for the maintenance period).

The primary endpoint is the average daily dose of extended-release oxymorphone, measured in mg from Day 1 up to Day 112. The registry describes this as an exposure outcome and says it was based on drug-accountability data from case report forms. The endpoint is intended to describe how much extended-release oxymorphone participants took during the study periods, rather than directly measuring pain relief or comparing treatments.

For a continuous measure, the mean represents the average across the observations included in the analysis. The standard deviation describes how spread out those observations are around the mean. These are general statistical interpretations; the registry record does not report the endpoint’s mean or standard deviation, so neither the average recorded dose nor its variability can be interpreted from the posted results.

Exposure is relevant to understanding the treatment participants received, particularly in a study with titration followed by maintenance at a fixed dose. However, an exposure measure alone does not show whether pain changed, whether participants benefited, or how the treatment compares with another option. The registry record does not report a numerical primary endpoint result or a corresponding confidence interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a continuous primary outcome summarized using a mean and standard deviation. It does not report a statistical analysis plan, an inferential analysis, or numerical estimates for this endpoint. The explanations below describe general statistical concepts relevant to this kind of outcome; they do not claim that any particular analysis was performed in this study.

What does the mean describe?

For a continuous measure, the mean is the arithmetic average of the observations included in the analysis. Here, the measure is average daily dose of extended-release oxymorphone in mg, calculated from drug-accountability information. Its interpretation depends on which participants and days contribute data. The endpoint description says the data are based on the number of enrolled participants in each treatment period, but does not specify the exact rules for handling incomplete records or observations across the timeframe.

A mean can be useful for describing the overall level of exposure, but it can conceal differences among participants. In a titration study, participants may have different recorded doses because doses were adjusted in response to review of pain scores and because maintenance followed individual titration. A group average alone would not show the range of individual doses, how many participants reached each dose, or whether exposure changed over time. Those details are not reported in the registry record.

What does the standard deviation add?

As a general statistical concept, the standard deviation describes the spread of observed values around their mean. A smaller standard deviation indicates values closer to the mean, while a larger one indicates greater dispersion. The standard deviation is not the same as the standard error, which describes the precision of an estimated mean. Neither measure can be interpreted for this primary endpoint because its numerical estimate and dispersion are not reported in the registry record.

When measurements vary substantially across participants, a single mean may be an incomplete description. General approaches can include reporting the distribution or using models suited to the data structure, but the choice depends on the observed data and analysis objective. The registry record does not report whether such methods were used or planned.

Why does the study structure matter?

This study is described as open-label and single-group. In general, an open-label design means treatment assignment is not masked from participants or study personnel. A single-group design has no concurrent control group. The titration and maintenance periods are successive stages of the study, rather than randomized groups assigned to different treatments. As a result, differences between period-specific descriptions would not by themselves isolate a treatment effect: participant composition and time under study can differ between periods.

The outcome timeframe spans Day 1 up to Day 112, covering the titration and maintenance periods as described in the record. The primary endpoint description says all participants entering maintenance finished titration. This does not mean all enrolled participants entered maintenance, nor does it describe their complete follow-up or endpoint data. The record does not report participant-level data or an analysis accounting for repeated measurements over time.

How should uncertainty be assessed?

In general, a confidence interval gives a range of values compatible with the data under a specified statistical method and assumptions. Its width conveys precision: wider intervals indicate less precision than narrower ones. A confidence interval is not reported for the primary endpoint in the registry record. There are also no reported p-values or other inferential results for that endpoint, so statistical significance or precision cannot be evaluated from the record.

Confidence intervals and tests would not resolve the absence of a control group. Even precise descriptive estimates in a single-group study do not establish what would have happened under a different treatment or without treatment. In general, causal comparisons require an appropriate contrast and design, and the registry record describes neither a randomized comparison nor a concurrent control.

What do planning illustrations mean?

In general, a sample-size calculation illustrates the number of participants needed under stated assumptions about the effect to detect, variability, significance level, power, allocation, and analysis method. The registry record does not report a protocol-based sample-size justification. Any sample-size figures derived from an observed effect are planning illustrations, not observed power and not evidence that a study was adequately or inadequately powered. Such illustrations depend on their assumptions and do not replace a study’s own design rationale or address the limitations of a single-group study.

The registry record lists 0 analyses. That absence means no inferential analysis is reported in the record; it does not establish what analyses may have been conducted outside the registry record. In particular, no adjusted estimate, hypothesis test, or model for the continuous endpoint is described.

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("Titration Period", "Maintenance Period")
n   <- c(27, 24)
m   <- c(35.25, 39.11)
sp  <- c(11.955, 15.176)
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  Titration Period  27  35.250  11.955  30.521  39.979
CARM  Maintenance Period  24  39.110  15.176  32.702  45.518

11. Multiplicity, Missing Data and Analysis Populations

The record lists five outcome measures: the primary exposure endpoint and four secondary measures concerning extended-release tablet use and immediate-release rescue medication. It does not report a statistical analysis plan, testing hierarchy, adjustment for multiple comparisons, or inferential analyses. Therefore, it is not possible to determine whether multiplicity was addressed in any analysis outside the registry record. In general, when several outcomes are tested, the chance of at least one apparently notable result can increase if no adjustment or hierarchy is used; this is a general statistical concern, not a claim that such testing occurred in this study.

Missing-data handling is not reported in the registry record. The description says the primary endpoint is based on drug-accountability information and the number of enrolled participants in each treatment period. It also says all participants entering maintenance finished titration. These statements do not specify whether every participant had complete endpoint information, how missed or incomplete drug-accountability records were treated, or how participants who did not enter maintenance were handled in analyses.

The safety population is defined as all participants who took at least 1 dose of study medication. The registry does not describe a separate efficacy population or provide analysis-specific participant counts for the primary endpoint. It also does not report an approach to censoring, imputation, sensitivity analyses, or other methods for incomplete follow-up.

Without those details, the potential influence of missing observations and the exact analysis populations cannot be assessed. The reported safety denominators remain interpretable as period-specific counts at risk, but they do not establish completeness of the exposure endpoint data.

12. 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: sickle cell anemia with crisis (4.2%), acute pancreatitis (4.2%), abdominal pain (4.2%), dyspnea (4.2%), increased alanine aminotransferase (4.2%).

The registry reports serious adverse events by treatment period. During titration, 0 of 27 participants at risk had a reported serious adverse event; during maintenance, 3 of 24 at risk did. No deaths are listed in either period. Other adverse events are reported for 15 of 27 at risk during titration and 7 of 24 at risk during maintenance.

These are descriptive period-specific counts, not a controlled comparison. The study was single-group, and titration and maintenance were sequential stages. The counts should not be interpreted as a randomized comparison or as evidence that risk differed between periods. The registry record does not report a statistical comparison, whether individual participants experienced events in both periods, or the timing and duration of each participant’s exposure.

The listed serious-event terms are sickle cell anemia with crisis, acute pancreatitis, abdominal pain, dyspnea, increased alanine aminotransferase, and increased aspartate aminotransferase, each reported as 4.2%. The record does not give enough detail to infer event causation or to translate these terms into a comparative risk estimate. The study’s early termination is attributed to a change in the FDA postmarketing requirement, and the record explicitly says it was not terminated for safety reasons.

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

The registry record describes a study intended to characterize exposure to extended-release oxymorphone during titration and maintenance in opioid-tolerant pediatric subjects with chronic pain. It also reports period-specific adverse-event counts. These details help define the study’s scope, but the primary outcome’s numerical mean and standard deviation are not reported in the registry record.

Without the primary endpoint estimate, the posted results do not show the average daily dose observed or how much dose varied among participants. They also do not provide a numerical estimate of pain relief or a comparison with another treatment. Although the study summary says titration was intended to end once a fixed dose was tolerated and adequate analgesia achieved, that description is not a reported result demonstrating that participants reached those conditions.

The design was open-label and single-group, with no concurrent control. Thus, the study cannot provide a randomized estimate of how outcomes would differ under another treatment. Exposure and safety counts can be described for the study participants, but they should not be interpreted as controlled treatment effects. The sequential titration and maintenance periods are not equivalent to independent comparison arms.

The reported safety counts include 0 of 27 at risk with serious adverse events during titration and 3 of 24 at risk during maintenance, with no deaths listed in either period. Other adverse events are listed for 15 of 27 and 7 of 24 at risk, respectively. These findings are descriptive, and the record does not report statistical tests or comparative safety analyses. The stated reason for termination was a change in the FDA postmarketing requirement, not safety.

Overall, the registry supports an understanding of the study design, its intended exposure endpoint, and its reported safety counts. It does not report enough outcome or analysis detail to quantify the primary exposure result, assess its precision, or draw conclusions about comparative efficacy or causality.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between measuring treatment exposure and measuring treatment effect. Its primary endpoint is average daily dose of extended-release oxymorphone, based on drug-accountability records. That endpoint can describe medication use, but it does not directly answer whether pain improved or how outcomes compare with another treatment.

The design also illustrates why treatment stages should not be mistaken for control groups. Participants moved through titration and, for those who entered it, maintenance. The study was open-label and single-group, so period-specific counts do not constitute a randomized comparison. Changes in who is observed across stages or how long each person is followed can complicate comparisons between periods.

Interpretation is further constrained by what is not reported: the primary endpoint’s numerical result and variability, inferential analyses, missing-data methods, and a protocol-based sample-size justification. Without those elements, readers cannot assess precision, analytical choices, or how complete the outcome data were. The fact that the record lists 0 analyses is especially important: the posted information is descriptive rather than a report of hypothesis testing.

The record also identifies a non-safety reason for early termination: a change in the FDA postmarketing requirement. That context prevents the termination status from being read as evidence of a safety-driven decision, while leaving open how early termination affected the amount and completeness of collected data. The trial therefore offers a useful example of how registry design details and reporting gaps shape what can be concluded from a clinical study record.

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 main limitation for statistical interpretation is that the numerical primary endpoint result is not reported in the registry record. Although the endpoint is defined as average daily dose of extended-release oxymorphone in mg, the record does not provide its mean or standard deviation. This prevents assessment of the observed dose level, variability, or precision.

The study is open-label and single-group, with no concurrent comparator. Its titration and maintenance stages cannot be treated as like-for-like control arms. Accordingly, the design does not support a randomized treatment comparison, and the registry record does not report a causal estimate.

The registry states that the study was terminated early because of a change in the FDA postmarketing requirement, not for safety reasons. It does not report how early termination affected participant follow-up, endpoint completeness, or the number of observations contributing to each outcome. Although all participants entering maintenance finished titration, the reasons other participants did not enter maintenance are not reported in the registry record.

Methods for handling missing data, outcome-specific analysis populations, statistical models, confidence intervals, and hypothesis tests are not reported. The record also does not report a protocol-based sample-size justification or a multiplicity approach. The safety counts are descriptive, and further detail about event timing, overlap across periods, and comparative analyses is not reported.

These limitations restrict interpretation of both the exposure endpoint and safety information. They do not establish that unreported analyses were never performed; they mean those methods and results cannot be evaluated from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-Label Safety and Tolerability of Oxymorphone IR and ER in Opioid Tolerant Pediatric Subjects — NCT00765856.
• Registry record last updated 2020-12-16; status last verified 2020-11.
• Results first posted 2020-12-16.
• 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

NCT00765856 is a Phase 3, open-label, single-group study of extended-release oxymorphone in opioid-tolerant pediatric subjects with chronic pain. Enrollment was 27. The study started on 2008-11-17, primary completion was 2010-02-22, and the status is terminated.

The primary endpoint was average daily dose of extended-release oxymorphone in mg from Day 1 up to Day 112, based on drug-accountability data. Its numerical result and standard deviation are not reported in the registry record. The record lists four secondary exposure outcomes and 0 analyses.

Serious adverse events were reported for 0 of 27 at risk during titration and 3 of 24 at risk during maintenance; no deaths were listed. The sponsor ended the study early because of a change in the FDA postmarketing requirement, not for safety reasons.