Phase 2B Study Assessing Pain Relief After Replacement of the Knee: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2B Study Assessing Pain Relief After Replacement of the Knee (NCT06799845), a randomized phase 2 study. The primary outcome is Area Under the Curve (AUC) for the Numerical Rating Scale at Rest (NRS-R) of Pain Intensity From 30 Minutes Through 168 Hours (Day 8) Compared to Placebo.

2. Clinical Question

3. Trial Design

The registry identifies NCT06799845 as a Phase 2B study of ATX101 in adults undergoing total knee arthroplasty. It describes a randomized, quadruple-masked, parallel-group trial with placebo and active-comparator control. The listed interventions are ATX101, saline placebo, and bupivacaine hydrochloride. The study summary identifies the clinical context as primary unilateral knee replacement and says efficacy, safety, opioid consumption, and tolerability were assessed.

The registry lists enrollment of 226 and a status of completed. The recorded start date is 2025-02-03 and the primary completion date is 2025-10-03. The primary outcome is the ATX101-versus-saline-placebo comparison in the FAS, described as per protocol. The result data give 89 participants for ATX101 and 93 for placebo for this endpoint. Those outcome counts are not the same information as the registry’s overall enrollment figure, and the registry record does not explain the difference.

Bupivacaine hydrochloride is an active comparator in the overall trial, but the primary endpoint result compares ATX101 with placebo. The registry record does not report the allocation ratio, the detailed masking procedures, the planned sample-size justification, or the trial’s original assumptions for selecting its enrollment target. The record also does not describe the exact content of each arm beyond naming the interventions. Those omissions limit what can be inferred about operational details, but do not change the stated primary comparison.

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: Started includes all participants who were screened and randomized. Participants enrolled includes only those who received investigational product during surgery. Enrolled participants does not include participants deemed randomization failures.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) ATX101 group compared to saline placebo group per protocol

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: Full Analysis Set (FAS)

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Curve (AUC) for the Numerical Rating Scale at Rest (NRS-R) of Pain Intensity From 30 Minutes Through 168 Hours (Day 8) Compared to Placebo, measured over from 30 minutes through 168 hours (Day 8).

The primary endpoint is the area under the curve for the Numerical Rating Scale at Rest (NRS-R) pain-intensity measure from 30 minutes through 168 hours (Day 8). The scale is described as an 11-item scale from 0 to10, with 0 meaning No Pain and 10 meaning Worst Imaginable Pain. The endpoint unit is score on a scale*hours, and the reported summary is a mean with standard deviation.

As a general statistical explanation, an AUC condenses measurements made over time into one cumulative measure. It reflects both the levels recorded and the period over which those measurements are accumulated. Here, the endpoint represents pain intensity at rest across the stated time window rather than a single rating at one time point. Its interpretation therefore depends on the full measurement window and on how the repeated ratings contribute to the AUC.

The registry record names pain intensity at rest as the primary outcome and gives the comparison with placebo. AUC is useful when an outcome is measured repeatedly because it supplies one summary for a defined period, which can be compared between groups. It does not, by itself, show the pattern of pain ratings at each individual time or identify when any group difference might have occurred. The registry record does not report further details about the measurement schedule or the construction of the AUC beyond the endpoint description.

7. Results Posted in the Registry

• ATX101: mean 980.61 versus 985.19 on control; difference -4.58 (95% CI -83.96 to 74.80), standardized effect d = -0.02; z-test p = 0.910.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

AUC for the NRS-R of Pain Intensity From 30 Minutes Through 336 Hours (Day 15) Compared to Placebo

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • ATX101: mean 1,812 versus 1,813 on control; difference -1.16 (95% CI -164.01 to 161.69), standardized effect d = -0.00; z-test p = 0.989.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ATX101 and the control. The interval gives the range of effects that remain compatible with the data.

AUC for the NRS-R of Pain Intensity From 30 Minutes Through 504 Hours (Day 22) Compared to Placebo

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • ATX101: mean 2,545 versus 2,537 on control; difference 8.66 (95% CI -241.31 to 258.63), standardized effect d = 0.01; z-test p = 0.946.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ATX101 and the control. The interval gives the range of effects that remain compatible with the data.

Total Post-surgical Consumption of Opioid Medications From 30 Minutes Through 336 Hours (Day 15) Compared to Placebo

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • ATX101: mean 233.42 versus 229.26 on control; difference 4.16 (95% CI -53.53 to 61.84), standardized effect d = 0.02; z-test p = 0.888.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ATX101 and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes involving pain AUC at later time windows, opioid consumption, pain during the Timed Up and Go test, and comparison with an active comparator. Across the posted placebo-comparison results with numerical summaries, the group means are close and the reported ANOVA p-values are not suggestive of clear statistical separation. This broad pattern aligns with the primary comparison, which also shows a small estimated difference and a confidence interval spanning zero. The secondary results add context but do not transform the primary finding into evidence of equivalence or establish a clinical interpretation.

The registry record lists five secondary outcomes, but numerical results for every listed secondary outcome are not reported in the registry record. In particular, the outcome list includes a pain AUC comparison with the active comparator and a Day 15 pain measure during the Timed Up and Go test; numerical results for these are not reported in the registry record. Conclusions about the complete set of secondary outcomes therefore cannot be drawn from the outcome names alone.

As a general statistical concern, examining multiple outcomes creates more opportunities for apparently notable findings to arise by chance. Unadjusted secondary results do not account for that multiplicity, and the registry record does not report a multiplicity adjustment or a prespecified hierarchy for secondary testing. Outcomes may also be correlated, so they should not be treated as wholly independent replications. The secondary findings are best viewed as exploratory or supportive context unless a prespecified testing strategy is reported. They should not outweigh the primary endpoint or be selectively emphasized based only on the size of a p-value.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• AUC for the NRS-R of Pain Intensity From 30 Minutes Through 336 Hours (Day 15) Compared to Placebo
• AUC for the NRS-R of Pain Intensity From 30 Minutes Through 504 Hours (Day 22) Compared to Placebo
• Total Post-surgical Consumption of Opioid Medications From 30 Minutes Through 336 Hours (Day 15) Compared to Placebo
• AUC for the NRS-R of Pain Intensity From 30 Minutes Through 336 Hours (Day 15) Compared to Active Comparator
• Difference in NRS-A Pain Intensity Scores During the Timed Up and Go (TUG) Test at Day 15 Compared to Placebo

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it is a mean AUC measured in score on a scale*hours. The registry reports each group’s sample size, mean, and standard deviation. These summaries describe the analyzed data, but they do not convey the complete distribution of individual participants’ AUC values. The standard deviation describes variability among observations within each group; it is not the same quantity as uncertainty around the estimated group mean.

What does a mean difference describe?

A mean difference expresses the average outcome in one group relative to the average in the comparator group, using the endpoint’s measurement units. For the primary result, the recalculated difference is -4.58 for ATX101 relative to saline placebo. The negative sign indicates that the ATX101 group mean is lower in the stated subtraction order. Because the endpoint is an AUC, this is a difference in cumulative score-times-hours, not a difference in a single NRS-R rating. The size and clinical meaning of a difference require context, including a clinically important threshold; that threshold is not reported in the registry record.

What does the confidence interval add?

A confidence interval represents uncertainty around an estimated effect under the assumptions of the analysis. It describes a range of values compatible with the observed data and method, rather than a guarantee that the true effect lies within the displayed limits. The primary interval runs from -83.96 to 74.8. Because it includes zero and values in both directions, it does not identify a clear direction of difference. Its span also indicates that the estimate is not highly precise. The interval should be read alongside the point estimate, group summaries, and study design rather than as a stand-alone verdict.

What is the role of the ANOVA result?

The sponsor reports an analysis of variance (ANOVA) for the primary comparison, with p = 0.901. As a general explanation, ANOVA tests whether the observed group pattern is compatible with a null model of no group difference, given the model and its assumptions. A p-value is not the probability that the null hypothesis is true, nor is it a measure of the size or importance of an effect. The registry record does not report the full ANOVA model specification, diagnostic checks, or any covariates used. The posted p-value should therefore be interpreted as the sponsor’s reported result, not as a complete description of the analysis.

The recalculated comparison uses the posted group summaries to derive a simple unadjusted mean difference and interval. Such a calculation does not reproduce all features that might have been included in a trial analysis plan. In this record, the sponsor’s p-value and the recalculated unadjusted p-value are similar, but the sponsor’s own analysis remains the trial’s reported inferential analysis. The recalculation is useful as a transparent summary check, not as a replacement for the sponsor’s analysis.

Why does variability matter?

The group standard deviations are substantial in relation to the estimated mean difference. As a general statistical point, when participant outcomes vary considerably within groups, a given sample may estimate the group means less precisely. The standard errors describe uncertainty in those estimated means, while the confidence interval for the difference accounts for uncertainty in the comparison. A small observed difference against considerable variability can therefore be estimated with limited precision. This is one reason a point estimate alone cannot establish that groups are alike.

General statistical methods also rely on assumptions about the data and analysis. AUC values are continuous summaries, and ANOVA is a common method for comparing means, but the registry record does not report distributional diagnostics, transformations, covariate adjustment, or handling of influential observations. No claims about those choices can be made from the posted information. The reported group means and inferential results should be understood within that limitation.

Why can over-dispersion matter?

As a general explanation, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a method underestimates variability, its standard errors and confidence intervals may be too small, making evidence appear more precise than it is. This concern is especially relevant for outcomes whose variability differs from a model’s assumptions. The present primary outcome is reported as a continuous AUC with standard deviations, and the registry record does not identify an over-dispersion issue or a specific adjustment for one. Therefore, over-dispersion should not be asserted as a demonstrated problem in this trial; it is a general reason to examine model assumptions and reported methods.

The primary comparison concerns ATX101 and placebo in the stated analysis population. Although the study included an active comparator, the reported primary ANOVA is between the ATX101 and saline placebo groups. The registry record does not report an inferential primary comparison against bupivacaine hydrochloride. Keeping those comparisons distinct avoids attributing a result from one comparison to another.

11. Confidence Intervals and Precision

The primary recalculated mean difference is -4.58, with a 95% confidence interval from -83.96 to 74.8. This interval crosses zero and includes both a lower mean AUC for ATX101 and a higher mean AUC for ATX101 relative to placebo. The point estimate is close to zero on the endpoint’s score-times-hours scale, but the interval is much wider than the estimate. The data therefore do not pin down the size or direction of the difference with high precision.

A confidence interval is an uncertainty summary under the specified calculation and its assumptions. It is not a range of outcomes for individual participants and does not mean that every value inside it is equally likely. The interval also does not determine whether a difference would be clinically important: the registry record does not report a threshold for that judgment. The sponsor’s ANOVA p-value is 0.901, while the simple unadjusted recalculation gives p = 0.91. The reported confidence interval and test result tell a consistent broad story of no clear statistical separation, while leaving meaningful uncertainty about the underlying difference.

For context, the two group means are 980.6 for ATX101 and 985.2 for saline placebo; the standard deviations are 280.7 and 264.9. A general statistical principle is that the precision of a mean comparison depends on sample size and variation, as well as the analysis method. The registry record does not report a prespecified precision target or a clinically important difference for this outcome. Consequently, the confidence interval is best read as a description of the uncertainty in the observed comparison, not as proof of equivalence or a definitive measure of clinical relevance.

12. 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 sample-size illustrations express the number of participants per arm for the continuous-outcome comparisons. They do not give total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column means the illustrated number of participants per arm under which a study would have an 80% chance of detecting the specified effect if that effect and the planning assumptions were correct. The 90% power column uses a higher target probability of detection and therefore generally calls for more participants per arm. These are planning illustrations rather than a description of the actual trial design. They are not observed power.

Rows that plan for 75% or 50% of the observed effect ask what enrollment would be needed to detect a smaller effect than the one estimated in this trial. Smaller effects are harder to distinguish from random variation, so they require more participants under the same assumptions. The displayed values can become very large when the observed effect is close to zero, as it is for the primary comparison. That behavior reflects how the illustration is calculated from the observed effect; it should not be interpreted as a recommended enrollment target or as a judgment about the appropriate design for a future trial.

These calculations also simplify the setting through equal allocation and a normal approximation. They do not establish the sample size that would be needed under a different endpoint, analysis plan, population, or target effect. The registry record does not state that these illustrations were used to plan the completed study.

13. 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 = -4.580; pooled standard deviation σ = 272.784.
2. n = 2 × (1.96 + 0.842)² × 272.784² / -4.580² = 55,685.9, rounded up to 55,686 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 <- -4.58000000000004                      # observed difference in means
sigma <- 272.784323181642                     # 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(6799845)
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 = 55,686 (80% power), 74,548 (90% power)
 75% of observed effect: n per arm = 98,998 (80% power), 132,530 (90% power)
 50% of observed effect: n per arm = 222,744 (80% power), 298,191 (90% power)
power.t.test: 55686.9 
Simulated power at n = 55,686 per arm: 0.801 (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.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as an ANOVA with p = 0.901. A simple unadjusted recalculation from the posted group summaries gives a mean difference of -4.58, a 95% confidence interval from -83.96 to 74.8, and p = 0.91. The p-values are close, and both indicate that the posted data do not show a clear statistical separation for the primary endpoint.

The recalculation is a summary-based check. It is not a reconstruction of every detail of the trial’s analysis, because the registry record does not report the full model specification or all analysis procedures. It should not be treated as an alternative sponsor analysis. The sponsor’s reported analysis is the formal result in the registry record, while the recalculation helps interpret the direction, magnitude, and uncertainty using the group summaries.

The record does not indicate a discrepancy between these results. Still, the sponsor’s own analysis takes precedence as the reported trial analysis. Neither p-value alone establishes equivalence, clinical importance, or the probability that a treatment effect exists. Interpretation also depends on the estimated difference, its uncertainty, the endpoint definition, and the analysis population.

15. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary endpoint and multiple secondary outcomes. It gives a sponsor ANOVA result for the primary comparison and reports analyses for listed outcomes, but the registry record does not report how multiplicity across outcomes or comparisons was handled. It does not state whether any secondary endpoints were arranged in a testing hierarchy, whether adjustments were used, or whether the inferential tests were intended to support confirmatory conclusions.

This matters because repeated testing across several outcomes can increase the chance of at least one apparently unusual result even when there is no underlying group difference. As a general statistical explanation, multiplicity procedures control or otherwise address that issue by accounting for the number and structure of tests. Without a reported approach, secondary p-values should be interpreted cautiously and should not be treated as if each were the only analysis undertaken. The primary endpoint remains the clearest reference point for the trial’s stated main question.

The registry record identifies the primary analysis population as the Full Analysis Set (FAS) ATX101 group compared to saline placebo group per protocol. It does not provide a detailed definition of the FAS, specify the exact analysis denominator rules, or describe how protocol deviations affected inclusion. It also does not report how missing outcome measurements were handled, whether imputation was used, or whether sensitivity analyses assessed missing-data assumptions. These details can affect the interpretation of estimates when outcomes are not observed for every participant.

The outcome summaries give analyzed group counts of 89 for ATX101 and 93 for placebo for the primary and several secondary comparisons. The record separately lists enrollment of 226, but does not explain how participants moved from enrollment to these analysis counts or give reasons for any differences. It would be inappropriate to infer dropout, exclusions, or missingness patterns from those figures alone. The absence of reported detail is a limitation in judging the robustness of the analyses, not evidence that a particular problem occurred.

16. 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: heart rate increased (2.3%), respiratory rate increased (2.3%), liver function test increased (2.2%), muscle spasms (1.1%), hepatitis a (1.1%).

The serious adverse event summaries report 9 affected participants among 90 at risk in the ATX101 group, 5 among 92 at risk in the saline placebo group, and 1 among 44 at risk in the bupivacaine hydrochloride group. The registry reports zero deaths in each of these groups. These are counts of participants affected, not counts of all event episodes, and the record does not provide a comparative statistical analysis for these figures.

The listed serious adverse event terms include Heart rate increased and Respiratory rate increased at 2.3% each, Liver function test increased at 2.2%, Muscle spasms and Hepatitis A at 1.1% each, and Pilonidal disease at 1.1%. These entries describe reported events; they do not establish that an intervention caused them. Counts should be interpreted in light of the different group sizes and the trial context, not as definitive estimates of comparative risk.

The registry also reports other adverse events affecting 71 of 90 ATX101 participants, 81 of 92 placebo participants, and 35 of 44 bupivacaine hydrochloride participants. The record does not provide enough detail to characterize event severity, timing, relatedness, or differences in monitoring. These summaries alone cannot resolve the overall safety and tolerability profile.

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

The primary result describes a comparison of mean pain-intensity AUC at rest between ATX101 and saline placebo, from 30 minutes through 168 hours (Day 8), in the stated analysis population. The mean difference is -4.58, and the sponsor reports p = 0.901. The confidence interval from -83.96 to 74.8 spans zero and includes values in either direction. In this analysis, the posted results do not show a clear statistical difference between the groups.

That finding does not prove that the treatments are equivalent, that their effects are exactly the same, or that a clinically meaningful difference is impossible. The confidence interval leaves uncertainty about the size and direction of the difference. The registry record does not report an equivalence or non-inferiority design, a margin for such a claim, or a clinically important threshold for the AUC endpoint. A non-significant superiority test cannot substitute for those elements.

The result also does not answer every question raised by the trial. The study summary includes opioid consumption, safety, and tolerability, and the registry lists several secondary outcomes. Some listed secondary outcomes do not have numerical results reported in the registry record. The primary pain result should not be used to infer effects on every secondary measure, on the active-comparator arm, or on outcomes outside the stated time window.

Finally, the reported comparison applies to the analyzed participants and trial setting. The registry record does not provide all details needed to assess missing data, model assumptions, multiplicity, or generalizability. Statistical interpretation should therefore stay close to the recorded endpoint, groups, and analysis, without turning an uncertain estimate into a treatment recommendation.

18. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should go beyond whether a p-value crosses a conventional threshold. The primary mean difference is close to zero, but the confidence interval extends in both directions and remains broad. The interval communicates uncertainty about the effect’s size more directly than a binary label of significant or not significant.

It also shows the distinction between an observed estimate and a planning target. Sample-size illustrations based on a very small observed effect can produce very large participant requirements, especially when the intended effect is made smaller. Those numbers are consequences of the stated planning assumptions, not a retrospective measure of whether the completed study had sufficient power and not evidence that the trial was originally planned that way.

The registry includes placebo and active-comparator groups, but the primary inferential result is the ATX101-versus-placebo comparison. Keeping the comparison groups clear is essential when interpreting a multi-arm trial. Likewise, the trial’s secondary outcomes broaden the questions under consideration, but unadjusted tests across multiple outcomes need cautious interpretation when the multiplicity plan is not reported.

Finally, the record shows how reporting detail shapes statistical conclusions. Group summaries and an ANOVA p-value are available, while important elements such as the full model, missing-data procedures, and multiplicity strategy are not reported. A clear account of both results and uncertainty is therefore central to understanding what the registry can—and cannot—establish.

19. 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 trial-specific limitations affect interpretation. The primary endpoint is a cumulative pain AUC through Day 8, so the single summary does not reveal how pain ratings varied at individual measurement times. The registry record does not report the measurement schedule or any threshold for a clinically important difference in this endpoint. It is therefore difficult to connect the observed mean difference to a clinical benchmark.

The primary analysis is described as involving the FAS ATX101 group compared with saline placebo per protocol, but the registry record does not define the analysis population in detail. It does not explain the difference between overall enrollment of 226 and the outcome counts of 89 for ATX101 and 93 for placebo. Reasons for any exclusions or unavailable measurements are not reported in the registry record, so participant flow and the possible effects of missing data cannot be assessed from these summaries.

The sponsor reports ANOVA, but model specification, assumptions, covariate use, and diagnostic checks are not reported in the registry record. The multiplicity approach for several secondary outcomes is also not reported. Numerical findings for every listed secondary endpoint are not reported in the registry record, limiting evaluation of the full outcome pattern. The study includes bupivacaine hydrochloride, but the primary result is the placebo comparison; the registry information summarized does not support conclusions about the active-comparator comparison.

Finally, the record does not report the original sample-size justification or planned effect assumptions. The separate planning illustrations are based on the observed effect and should not be treated as a description of the trial’s original design. These reporting gaps do not show that the analyses were inappropriate; they limit independent assessment of their assumptions and robustness.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Phase 2B Study Assessing Pain Relief After Replacement of the Knee — NCT06799845.
• Registry record last updated 2026-10-19; status last verified 2026-10.
• Results first posted 2026-10-19.
• 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.

23. Record Summary

NCT06799845 is a completed Phase 2B randomized, quadruple-masked, parallel-group trial of ATX101 in adults undergoing total knee arthroplasty. The registry lists enrollment of 226 and includes saline placebo and bupivacaine hydrochloride as comparators. The primary outcome compares ATX101 with saline placebo on mean NRS-R pain-intensity AUC from 30 minutes through 168 hours (Day 8).

The primary group means were 980.6 for ATX101 and 985.2 for placebo. The sponsor’s ANOVA result was p = 0.901; the recalculated unadjusted mean difference was -4.58, with a 95% confidence interval from -83.96 to 74.8. The result does not show a clear statistical separation, while the interval leaves uncertainty about the size and direction of the difference. Secondary outcomes and serious adverse event summaries provide additional context, but details on multiplicity, missing data, and the original sample-size justification are not reported in the registry record.