OXN PR Tablet 5/2.5 mg and20/10 mg PK Study in Chinese Moderate to Severe Chronic Non-malignant Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for OXN PR Tablet 5/2.5 mg and20/10 mg PK Study in Chinese Moderate to Severe Chronic Non-malignant Patients (NCT02880475), a randomized phase 1 study. The primary outcome is AUC0-48hr of Noroxycodone Plasma Concentration..

2. Clinical Question

3. Trial Design

NCT02880475 is listed as a completed Phase 1 study sponsored by Mundipharma (China) Pharmaceutical Co. Ltd. The registry describes a randomized, open-label, single-dose, parallel-group design. Its stated objective was to assess the pharmacokinetics of oxycodone and naloxone from OXN prolonged-release tablets at the 5/2.5 mg and 20/10 mg strengths in Chinese patients with moderate to severe chronic non-malignant pain.

Participants were assigned to receive a single dose of one tablet strength. The registry lists 30 enrolled participants. For the primary outcome, it describes 12 subjects in the OXN 5/2.5 mg group and 12 subjects in the OXN 20/10 mg group. Those outcome-population figures are the ones attached to the reported means and standard deviations. The record does not explain the difference between the enrollment figure and the primary outcome population description, so no reason for that difference can be inferred.

Blood sampling was scheduled before dosing and at the listed post-dose time points through 48 hours. The primary outcome was AUC0-48hr of noroxycodone plasma concentration. The registry's outcome description also refers to analysis of plasma concentrations for both OXN strengths and describes pharmacokinetic sampling for oxycodone and metabolites. The posted primary comparison specifically concerns noroxycodone.

The record identifies the study as randomized but does not report the randomization sequence method or allocation concealment. It states that masking was absent. The parallel design means that each assigned arm is compared with the other arm rather than with a participant's response to a second treatment period. Details of eligibility criteria, study sites, adherence, protocol deviations, and the original sample-size rationale are not reported in the registry 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

Analysis population for the primary outcome, as defined in the registry: 12 subjects in OXN PR tablet 5/2.5 mg group,12 subjects in OXN PR tablet 20/10 mg group.

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.

6. Primary Endpoint

The registry lists the primary outcome as AUC0-48hr of Noroxycodone Plasma Concentration., measured over Pre-dose, 0.5h, 1.0h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 7h, 8h, 10h, 12h, 14h, 24h, 28h, 32h, 36h, and 48h Post Dose blood sampling to determine the PK of oxycodone and metabolites in Chinese patients..

The primary endpoint is AUC0-48hr of noroxycodone plasma concentration, measured in hr*ng/mL. AUC, or area under the concentration-time curve, is a pharmacokinetic summary of drug-related concentration across a specified time interval. Rather than describing concentration at a single blood draw, it integrates the concentration measurements across the stated interval. The registry describes pre-dose and post-dose blood sampling through 48 hours for pharmacokinetic assessment.

Noroxycodone is a metabolite of oxycodone, and its plasma concentration is the substance named in this primary outcome. The endpoint is used to compare the amount of noroxycodone exposure observed after a single dose of each OXN tablet strength. It does not directly measure pain intensity, function, quality of life, or sustained effects during continued treatment. The study's objective includes pharmacokinetics of oxycodone and naloxone, but the primary outcome reported for this comparison is noroxycodone AUC.

The registry reports a mean and standard deviation for each group. The mean describes the group's average measured AUC; the standard deviation describes variation among the individual observations around that average. Those summaries do not show the full distribution of participant values. Interpretation therefore rests on the posted aggregate estimates and their uncertainty, rather than on individual concentration profiles.

7. Results Posted in the Registry

• OXN PR Tablet 20/10 mg: mean 325.51 versus 81.72 on control; difference 243.79 (95% CI 183.17 to 304.41), standardized effect d = 3.22; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The reported endpoint is a continuous measurement, summarized as a mean and standard deviation in each randomized arm. A continuous outcome can take values across a measurement scale rather than belonging to a limited set of categories. For this endpoint the scale is hr*ng/mL, and the outcome is accumulated noroxycodone plasma concentration over the stated interval.

What does a group mean describe?

A mean is the arithmetic average of the measured values in a group. It gives a central summary that can be compared between randomized arms. The posted mean is 81.72 hr*ng/mL for OXN PR Tablet 5/2.5 mg and 325.5 hr*ng/mL for OXN PR Tablet 20/10 mg. A mean alone does not show whether observations cluster near that value, are widely dispersed, or include unusually high or low values.

The standard deviation describes the spread of observations around the mean in the same units as the outcome. The registry reports standard deviations of 39.82 and 99.47 hr*ng/mL for the respective groups. Standard deviation is not the same as a confidence interval for a mean. It describes variability among observations, whereas a confidence interval addresses uncertainty in an estimated quantity such as a group mean difference.

What does the mean difference express?

The posted comparison reports a mean difference of 243.8 hr*ng/mL for the 20/10 mg group relative to the 5/2.5 mg group. A difference retains the outcome's units and describes the separation between group averages. It is not a ratio and does not express the relative increase in exposure. No ratio estimate is reported in the registry record. The comparison also reports a pooled standard deviation of 75.76 and a standardized effect measure of 3.218. A standardized effect expresses a difference on a scale that accounts for variability, rather than in hr*ng/mL. These summaries do not by themselves describe clinical importance.

How should the p-value be understood?

The registry reports an unadjusted p-value of p < 0.001 for the mean comparison. In general, a p-value describes how incompatible the observed data, or more extreme data, are with a specified null hypothesis under the statistical model. It is not the probability that the null hypothesis is correct, and it is not a measure of the size or clinical relevance of an effect. The record does not identify the test used to obtain this p-value, so a specific test should not be assumed.

The word unadjusted matters because the result is reported without a stated correction for examining multiple outcomes or comparisons. The record lists 64 outcome measures and does not post secondary outcome results. It does not report a multiplicity strategy. The p-value should therefore be understood as the posted unadjusted result, not as an estimate adjusted for a broader testing plan.

What does a confidence interval add?

A confidence interval expresses uncertainty around an estimate. In general, a 95% confidence interval is generated by a method designed to cover the true parameter in 95% of repeated samples when its assumptions hold. It is not a statement that there is a 95% probability that the specific interval contains the fixed true value. For the mean difference, the reported interval is 183.2 to 304.4 hr*ng/mL. It conveys more information about the range of estimates compatible with the data and method than the p-value alone.

The interval also depends on assumptions and on how the estimate's standard error is calculated. The registry does not report the confidence-interval method, the test procedure, or diagnostic checks. The outcome-specific group sizes are reported as 12 in each arm, but the record does not describe whether all randomized participants contributed a measured endpoint or how missing values, if any, were addressed.

Why can variation affect interpretation?

In general, greater variability makes a group average less precise when other aspects of the design are held constant. Similar averages can be estimated with different precision depending on the spread of observations and the number contributing data. For continuous pharmacokinetic outcomes, values may be skewed or show unequal variability across arms. A normal-based method can be sensitive to departures from its assumptions, especially in small groups. Transformations, robust procedures, or models that account for distributional features may sometimes be considered, but the registry does not state that any such approach was used.

Over-dispersion, in general, means that observed variability is greater than a model assumes. If a model understates variability, its standard errors can be too small and its confidence intervals too narrow. That general concern cannot be assessed from means and standard deviations alone. The registry does not report individual data, distribution plots, model diagnostics, or an analysis method that would establish how variation was handled.

Randomization can support a comparison by reducing systematic differences between assigned groups on average, but the record does not describe sequence generation or allocation concealment. Open-label status means masking was absent, although the primary endpoint is a measured plasma concentration rather than a subjective rating. Neither design feature substitutes for a fully reported statistical analysis plan. The record does not report whether the posted comparison was prespecified in the original protocol, whether interim analyses were planned, or what model was used. Those details are not reported in the registry record and should not be inferred from the numerical result.

10. Confidence Intervals and Precision

The reported mean difference for noroxycodone AUC is 243.8 hr*ng/mL, and the 95% confidence interval runs from 183.2 to 304.4 hr*ng/mL. The interval provides a range of values compatible with the observed estimate under the method's assumptions. It is more informative about precision than the p-value alone, because it shows the estimated scale and direction of the difference as well as its uncertainty.

The entire reported interval is above zero. In general, when a confidence interval for a difference excludes zero, the data are inconsistent with a zero difference at the corresponding confidence level under the analysis assumptions. This does not show that the difference is clinically important, and it does not remove uncertainty about how well the statistical assumptions fit the data. The registry does not report the method used to form the interval, so its particular assumptions cannot be verified from the record.

The group standard deviations, 39.82 hr*ng/mL and 99.47 hr*ng/mL, describe variation among measured observations, not uncertainty in the mean difference itself. The outcome-specific group sizes are 12 in each arm. With these summaries, precision can be described through the posted interval, but the underlying distribution, influential observations, and potential missingness cannot be assessed.

The interval concerns a single-dose pharmacokinetic endpoint in the studied population. It does not quantify uncertainty about longer-term exposure, clinical outcomes, or effects in populations not described by this study. The posted precision is therefore specific to the reported comparison and endpoint.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures express participants per arm, not total events. They are illustrations based on the observed mean difference, not the original trial's sample-size rationale. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set as a stated fraction of the observed effect.

For planning for 100% of the observed effect, the figures are 2 participants per arm for 80% power and 3 participants per arm for 90% power. For planning for 75% of the observed effect, the figures are 3 participants per arm for 80% power and 4 participants per arm for 90% power. For planning for 50% of the observed effect, the figures are 7 participants per arm for 80% power and 9 participants per arm for 90% power.

Power is the probability that a study would meet its specified statistical criterion if the assumed effect and model were true. The 80% and 90% columns describe different target probabilities for detecting the assumed effect under the stated planning assumptions. Smaller effects are harder to distinguish from random variation and therefore require more participants under otherwise unchanged assumptions. The visual planning display should be read in the same way as these planning figures, not as a description of the original study's design.

These are planning illustrations, not observed power. The original study's sample-size assumptions and justification are not reported in the registry record. The calculated figures also do not establish that a future study should use these sizes; they depend on the assumed effect and the stated statistical framework.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 243.790; pooled standard deviation σ = 75.763.
2. n = 2 × (1.96 + 0.842)² × 75.763² / 243.790² = 1.5, rounded up to 2 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 243.79                      # observed difference in means
sigma <- 75.7625016086454                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2880475)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2 (80% power), 3 (90% power)
 75% of observed effect: n per arm = 3 (80% power), 4 (90% power)
 50% of observed effect: n per arm = 7 (80% power), 9 (90% power)
power.t.test: 2.9 
Simulated power at n = 2 per arm: 0.425 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists 64 outcome measures and posts no secondary outcome results. It reports a primary outcome comparison for noroxycodone AUC and gives an unadjusted p-value of p < 0.001. No analysis count is listed. The registry record does not report a multiplicity plan, such as which outcomes were designated primary in a hierarchy or how the chance of false-positive findings across multiple tests was handled.

Multiplicity matters when several outcomes, time points, or comparisons are examined. In general, the more statistical tests considered, the greater the opportunity for at least one result to appear unusual by chance if no adjustment or prespecified strategy is used. The 64 outcome measures may include different kinds of outcomes or measurements; the record does not explain their relationship to the primary result. It would therefore be inappropriate to infer the number of tests actually performed or to calculate an adjusted significance level.

The record does not describe missing-data procedures, exclusions from the primary analysis, or the analysis population definition. It identifies 12 subjects in each group for the primary outcome, while enrollment is listed as 30. It does not explain whether any participants lacked a usable endpoint or why the outcome-specific population figures differ from enrollment. No assumptions about imputation, complete-case analysis, or other missing-data handling can be made.

The randomization and arm descriptions establish the intended comparison, but the registry does not specify whether the primary analysis followed an intention-to-treat principle, a per-protocol approach, or another population definition. It also does not report a statistical analysis plan, the test used, adjustments for covariates, or interim analyses. These details are not reported in the registry record, so the posted unadjusted comparison should not be treated as a complete account of analysis choices.

14. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: upper respiratory tract infection (7.7%).

Serious adverse event figures are reported separately from the primary pharmacokinetic outcome. The registry lists 1 serious adverse event among 13 participants at risk in the OXN PR Tablet 5/2.5 mg group and 0 among 17 participants at risk in the OXN PR Tablet 20/10 mg group. It lists 0 deaths in each group. The reported serious adverse event term includes upper respiratory tract infection at 7.7%; the registry record does not provide further context for that percentage in the listed term summary.

Other adverse events are listed for 9 of 13 participants at risk in the 5/2.5 mg group and 13 of 17 in the 20/10 mg group. These are descriptive counts with their stated denominators. They should not be interpreted as evidence that one strength is safer or less safe: the record does not provide an adjusted comparison, a statistical uncertainty estimate for these counts, or sufficient detail about event severity and timing for such a conclusion.

The safety figures do not share the same group counts as the primary outcome description, which specifies 12 subjects in each arm. The registry does not explain this difference. Serious adverse events, other adverse events, and deaths are distinct categories in the record; they should not be combined. The posted figures describe events recorded during the study and do not establish long-term safety.

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

The result describes a difference in mean noroxycodone exposure after a single dose of two OXN prolonged-release tablet strengths among Chinese patients with moderate to severe chronic non-malignant pain. The mean AUC0-48hr was 81.72 hr*ng/mL in the 5/2.5 mg group and 325.5 hr*ng/mL in the 20/10 mg group. The reported mean difference was 243.8 hr*ng/mL, with a 95% confidence interval from 183.2 to 304.4 hr*ng/mL and an unadjusted p-value of p < 0.001.

Those results support a statistical description of the measured pharmacokinetic outcome in the randomized groups. They do not by themselves establish a difference in pain relief, daily functioning, quality of life, or other clinical outcomes. Nor do they determine whether the observed exposure difference is clinically meaningful. The registry does not report a threshold defining a clinically important difference for this endpoint.

The result concerns noroxycodone AUC over the stated interval after a single dose. It cannot be used to infer concentration profiles beyond the measured period, effects during repeated dosing, or outcomes after longer-term use. It is also not a comparison of the two components' isolated effects: both groups received OXN tablets, and the reported primary comparison is between strengths of the combination product.

The study's scope is limited to the population and design recorded: a Phase 1 randomized, open-label, parallel-group single-dose study in Chinese patients with moderate to severe chronic non-malignant pain. The posted result does not establish how well it generalizes to other populations or settings. The registry does not report enough information to assess the original sample-size rationale, missing-data handling, or the complete statistical plan. These limits do not negate the reported estimates, but they constrain the conclusions that can be drawn from them.

16. Why This Trial Matters Statistically

This study illustrates how a pharmacokinetic question can be framed as a comparison of continuous outcomes between randomized groups. The endpoint is an integrated exposure measure, AUC0-48hr, rather than a single concentration reading. Its units and interval make clear what is being compared: noroxycodone plasma exposure across the stated post-dose period.

The record is also a useful example of why effect estimates and uncertainty should be read together. The mean difference of 243.8 hr*ng/mL gives the estimated separation between group averages, while the confidence interval from 183.2 to 304.4 hr*ng/mL indicates the range of estimates compatible with the analysis. The unadjusted p-value adds a test-based summary but does not replace the estimate or interval, and it does not answer whether the difference has clinical importance.

Statistically, the study highlights the need to distinguish endpoint-specific analysis populations from overall enrollment. The registry lists enrollment of 30 but describes 12 subjects in each group for the primary endpoint. Without participant-flow or missing-data information, that distinction cannot be explained from the record. Clear reporting of analysis populations would help readers understand which observations contribute to each estimate.

The study also demonstrates the limits of interpreting a single posted comparison when a record lists many outcome measures. An unadjusted result has to be considered alongside the absence of a reported multiplicity strategy, statistical analysis plan, and missing-data procedure. These are reporting questions, not reasons to replace the posted effect estimate with speculation.

17. 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 record leaves several trial-specific questions unresolved. Although it lists enrollment of 30, the primary outcome description specifies 12 subjects in each dose group, and the means are attached to group sizes of 12. The record does not explain participant flow or why the enrollment and endpoint population descriptions differ. It also does not state how many participants were randomized, received a dose, completed sampling, or contributed to the safety summaries.

The design is described as randomized, but the sequence-generation and allocation-concealment methods are not reported. Masking was absent. The study was single-dose and parallel-group, so it does not report repeated-dose exposure or a within-participant comparison across strengths. Details of eligibility criteria, sites, adherence, concomitant medication, and protocol deviations are not reported in the registry record.

The registry does not report the statistical test or model for the mean comparison, the method used to calculate the confidence interval, diagnostic checks, transformations, or covariate adjustments. It does not specify missing-data handling, the analysis population, or an approach to multiplicity despite listing 64 outcome measures. The original sample-size rationale and any interim-analysis plan are also not reported in the registry record.

These gaps limit reproducibility and evaluation of assumptions. Aggregate means and standard deviations cannot reveal the shape of the outcome distributions or the influence of individual values. The safety summary provides counts but does not give a full account of event timing or exposure-adjusted rates. The posted estimates remain interpretable as the registry's reported summary, but the record does not support broader conclusions about clinical outcomes or longer-term safety.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: OXN PR Tablet 5/2.5 mg and20/10 mg PK Study in Chinese Moderate to Severe Chronic Non-malignant Patients — NCT02880475.
• Registry record last updated 2019-07-17; status last verified 2019-04.
• Results first posted 2019-07-17.
• 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.

21. Record Summary

NCT02880475 is a completed Phase 1 randomized, open-label, single-dose, parallel-group pharmacokinetic study sponsored by Mundipharma (China) Pharmaceutical Co. Ltd. It examined OXN prolonged-release tablets in Chinese patients with moderate to severe chronic non-malignant pain. The primary outcome was AUC0-48hr of noroxycodone plasma concentration.

The posted group means were 81.72 hr*ng/mL for OXN 5/2.5 mg and 325.5 hr*ng/mL for OXN 20/10 mg. The reported mean difference was 243.8 hr*ng/mL, with a 95% confidence interval from 183.2 to 304.4 hr*ng/mL and an unadjusted p-value of p < 0.001. The result concerns single-dose pharmacokinetic exposure, not clinical efficacy or long-term outcomes. Analysis methods beyond the posted summaries and key details on missing data and the original sample-size rationale are not reported in the registry record.