Cohort 2 (Abdominoplasty) of: A Multi-surgery Assessment of ZYNRELEF (HTX-011): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cohort 2 (Abdominoplasty) of: A Multi-surgery Assessment of ZYNRELEF (HTX-011) (NCT06109428), a randomized phase 4 study. The primary outcome is Incidence of TEAEs.

2. Clinical Question

The study is described as randomized, blinded, and active-controlled. Its clinical comparison is between two treatment regimens used in participants undergoing abdominoplasty; it is not a comparison with no analgesic regimen. The primary outcome therefore addresses recorded treatment-emergent adverse events during the stated timeframe. It does not, by itself, describe pain intensity, the amount of rescue analgesia used, or the duration of pain relief. Those outcomes are not reported in the registry record.

3. Trial Design

This record concerns Cohort 2, the abdominoplasty cohort, of a Phase 4 randomized, blinded, active-controlled study of HTX-011 across different surgical procedures. The study model is parallel. Participants were assigned to HTX-011 plus multimodal analgesia or bupivacaine HCl plus multimodal analgesia. The registry describes the study as double-blind, but which participants, clinicians, or assessors were masked is not reported in the registry record.

The HTX-011 regimen was 400 mg/12 mg via instillation with an oral multimodal analgesic regimen. The comparator was bupivacaine HCl 125 mg via injection with an oral multimodal analgesic regimen. Thus, the active comparison concerns the assigned local treatment within regimens that both included oral multimodal analgesia. Further details about the oral regimen are not reported in the registry record.

The registry lists enrollment as 37 and status as completed. The study start date is 2021-10-12, and the primary completion date is 2022-03-29. The posted primary outcome denominators are 22 for HTX-011 plus multimodal analgesia and 12 for bupivacaine HCl plus multimodal analgesia. Why those outcome denominators differ from the enrollment figure is not reported in the registry record; the record does not explain the participant flow or the analysis population used for this outcome.

The record identifies a separate master study protocol record, NCT05109312. Cohort-specific eligibility criteria, the method used to generate and conceal randomization, masking procedures, and the original sample-size justification 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

Reasons for not completing this period:

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: Number of subjects dosed

6. Primary Endpoint

The registry lists the primary outcome as Incidence of TEAEs, measured over Through Day 15.

The primary endpoint is the incidence of treatment-emergent adverse events through Day 15, expressed as the count of participants with an event. It is a safety outcome: it describes whether participants had recorded events emerging during the treatment period, rather than how many event episodes occurred in total. The registry lists 18 participants in the HTX-011 plus multimodal analgesia group and 9 in the bupivacaine HCl plus multimodal analgesia group as affected. The corresponding outcome denominators are 22 and 12.

Counting participants gives each person a place in the incidence measure, even if an individual experienced more than one event. The measure is therefore different from a count of all adverse-event episodes, and it does not convey event severity, duration, or clinical importance by itself. Serious adverse events are listed separately in the safety information.

In general, an adverse-event endpoint can help characterize events recorded during a defined follow-up period. It is not a direct measure of pain relief or analgesic effectiveness. The timeframe matters: this primary outcome covers through Day 15, and the completeness of follow-up for every participant is not reported in the registry record. The endpoint definition and its time window are posted, but additional operational details, such as the criteria used to classify an event as treatment-emergent, are not reported in the registry record.

7. Results Posted in the Registry

• Bupivacaine HCl + MMA: 75.0% (9/12) versus 81.8% (18/22) on control; risk difference -6.8 percentage points (95% CI -36.1 to 22.5), risk ratio 0.92 (0.63–1.34); unadjusted two-proportion z-test p = 0.638.

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.

Cmax

• 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:
  • Bupivacaine HCl + MMA: mean 290.00 versus 382.00 on control; difference -92.00 (95% CI -309.86 to 125.86), standardized effect d = -0.37; z-test p = 0.408.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Bupivacaine HCl + MMA and the control. The interval gives the range of effects that remain compatible with the data.

AUClast

• 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:
  • Bupivacaine HCl + MMA: mean 6,000 versus 23,900 on control; difference -17,900 (95% CI -22,303 to -13,497), standardized effect d = -2.23; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Bupivacaine HCl + MMA than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

AUCinf

• 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:
  • Bupivacaine HCl + MMA: mean 6,050 versus 24,400 on control; difference -18,350 (95% CI -22,767 to -13,933), standardized effect d = -2.28; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Bupivacaine HCl + MMA than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry names Cmax, Tmax, AUClast, AUCinf, and t½ as secondary pharmacokinetic outcomes. Numerical results are posted for Cmax, AUClast, and AUCinf; numerical results for Tmax and t½ are not reported in the registry record. The posted measures describe exposure through 144 hours, rather than patient-reported pain or the primary treatment-emergent adverse-event outcome.

Across the three outcomes with numerical results, the pattern is not uniform in its statistical separation. The Cmax mean-difference interval spans zero, whereas the AUClast and AUCinf mean-difference intervals do not. The latter estimates are in the direction of lower values in the bupivacaine HCl group compared with HTX-011, under the recorded contrast. These pharmacokinetic patterns concern measured exposure and should not be interpreted as evidence of comparative analgesic effect or as a replacement for the primary safety result.

The reported secondary comparisons are unadjusted. In general, when multiple outcomes are examined, the chance of observing an apparently notable result by chance can increase unless the analysis plan accounts for the number and structure of tests. The registry record does not report a multiplicity procedure or a prespecified hierarchy for these outcomes. For that reason, secondary results have less confirmatory weight than a result from a clearly prespecified, appropriately controlled primary analysis. The registry also lists no reported sponsor analyses for the secondary outcomes; the displayed comparisons are unadjusted recalculations from the posted summary statistics.

The secondary findings can help describe measured drug exposure in this cohort, but they do not resolve the imprecision of the primary adverse-event comparison. Nor can the unreported Tmax and t½ results be inferred from the other measures. No conclusion about pain control or a clinical benefit should be drawn from the pharmacokinetic measures alone.

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

• Cmax
• Tmax
• AUClast
• AUCinf
• t½

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant is counted as having or not having a treatment-emergent adverse event during the stated period. The posted group summaries are counts of affected participants and denominators. The observed proportions are 0.818 for HTX-011 plus multimodal analgesia and 0.75 for bupivacaine HCl plus multimodal analgesia. These are descriptive summaries of the participants included in the posted outcome data, not estimates adjusted for other participant characteristics.

The comparison uses a risk difference. In general, a risk difference subtracts one group’s event proportion from the other group’s event proportion, following a stated comparison direction. Here, the estimate is -0.068 for bupivacaine HCl plus multimodal analgesia relative to HTX-011 plus multimodal analgesia. A value of zero represents equal observed risks under that contrast; a negative or positive value indicates the direction of the estimated difference. The estimate is not a count of participants, and its uncertainty must be considered alongside its sign.

The record also gives a risk ratio of 0.917 and an odds ratio of 0.667. In general, the risk ratio compares event proportions, whereas the odds ratio compares event odds. Each uses a different scale and can give a different numerical impression, especially when outcomes are common. Neither measure removes uncertainty or turns an unadjusted comparison into an adjusted one. Their confidence intervals are reported with the primary comparison and should be read as ranges of values compatible with the data and method, not as guarantees about the true effect.

The p-value is unadjusted and reported as 0.638. In general, a p-value describes how unusual data at least as incompatible with a specified no-difference model would be if that model and the analysis assumptions held. It is not the probability that the no-difference model is true, and it does not measure the size or clinical importance of a difference. A p-value alone does not establish equivalence. The registry record does not identify a sponsor-reported analysis for this endpoint; the posted comparison is a recalculation from summary counts.

For continuous secondary outcomes, the record reports group means and standard deviations, then a mean difference and confidence interval. A mean difference expresses the difference between the two group averages on the outcome’s original measurement scale. The standard deviation describes variation among participant measurements within a group; it is not the same as the standard error of a mean or the width of a confidence interval. A confidence interval for a mean difference reflects uncertainty in the estimated contrast. The registry lists no reported analyses for these secondary outcomes either.

General statistical context: when participant outcomes are more variable than a model assumes, or when counts are sparse, standard errors and interval estimates can be unreliable unless the analysis accounts for that feature. For this primary endpoint, the registry does not report a particular model or test, nor does it describe any adjustment for covariates. It would therefore be inappropriate to attribute a specific modeling approach, correction, or testing procedure to the study. The estimates posted for the primary contrast are explicitly unadjusted.

Several pieces of information needed to reproduce or fully assess an analysis are not reported in the registry record. These include the analysis population, treatment of participants with missing outcome data, the method for handling multiple events in one participant, and the exact inferential procedure used for the primary comparison. The record also does not state whether any interim analyses were conducted or identify a prespecified statistical analysis plan for this cohort. These absences do not change the counts that are posted, but they limit how completely the statistical analysis can be evaluated.

The secondary outcomes Cmax, AUClast, and AUCinf are continuous pharmacokinetic measures. Cmax is reported in ng/mL; AUClast and AUCinf are reported in h∙ng/mL. Their timeframes are through 144 hours. In general, pharmacokinetic measures describe aspects of drug concentration over time. They do not directly measure postoperative pain, and their contrasts should not be substituted for the primary adverse-event comparison.

General statistical context: confidence intervals are useful because they show both the direction and the precision of an estimate. A narrow interval indicates more precision than a wide interval, while an interval spanning a no-difference value leaves uncertainty about direction. For a risk difference, the no-difference value is zero; for a ratio measure, it is one. These interpretive principles help distinguish the point estimate from the range of uncertainty around it. They do not replace clinical interpretation, and no clinical threshold for a meaningful difference is reported in the registry record.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.068, and its 95% confidence interval ranges from -0.361 to 0.225. Because the interval includes zero, the observed data do not distinguish a difference from no difference at the interval’s stated confidence level. Values on both sides of zero remain compatible with the posted data and analysis. The range is broad, so the estimate is not precise enough to establish a stable direction or tightly bounded magnitude of the difference.

In general, a confidence interval describes uncertainty in an estimate under the statistical method and assumptions used. It is not a range that contains a fixed proportion of individual participant outcomes, and it is not a statement that the true value has a particular probability of being inside this specific interval. The registry does not report the inferential method used for the primary interval, which limits a full assessment of its assumptions.

The ratio estimates also have broad intervals: the risk ratio is 0.917 with a confidence interval from 0.626 to 1.342, and the odds ratio is 0.667 with a confidence interval from 0.122 to 3.64. Both include one, the no-association value for a ratio. The intervals allow a range of possible comparative effects rather than identifying a precise effect. Differences in the numerical scales of risk differences and ratios mean that their estimates should be interpreted according to their definitions, not compared as though they were the same quantity.

The primary denominators are 22 and 12. With these relatively limited group sizes, the data provide limited precision for a binary outcome. The point estimate is only one component of interpretation; the interval and the small denominators are essential context. No clinically important difference threshold is reported in the registry record, so the intervals cannot be classified against a prespecified threshold for 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 planning figures are participants per arm for this trial’s non-time-to-event outcomes, including the binary primary endpoint. They are not total event counts. The record’s general rule for time-to-event outcomes is to give total events, but no time-to-event outcome is listed among the results.

These planning illustrations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to the stated fraction of the observed effect: 100%, 75%, or 50%. The calculations are illustrations based on the observed effect, not the trial’s original design assumptions. The original sample-size justification and assumptions are not reported in the registry record.

The 80% power column means the number of participants per arm estimated to give an 80% chance of detecting the specified effect under the planning assumptions, if that effect and those assumptions applied. The 90% power column uses the same idea with a higher target chance of detection. These are design-planning concepts, not probabilities that the observed result is correct. They do not describe the probability that this completed study detected an effect.

Read each effect scenario separately. Planning for 75% of the observed effect means targeting a smaller effect than planning for 100% of the observed effect; planning for 50% means targeting a still smaller effect. Smaller effects are harder to distinguish from random variation and therefore require more participants per arm under these calculations. The same direction applies when following the planning curve: moving toward a smaller target effect corresponds to a larger participant requirement. These figures are planning illustrations, not observed power.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.818; treatment proportion p₁ = 0.750; average p̄ = 0.784.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5819 = 1.1405.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5799 = 0.4880.
4. n = (1.1405 + 0.4880)² / (-0.0682)² = 570.5, rounded up to 571 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
p0 <- 0.818181818181818                          # control proportion
p1 <- 0.75                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(6109428)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 571 (80% power), 764 (90% power)
 75% of observed effect: n per arm = 986 (80% power), 1,319 (90% power)
 50% of observed effect: n per arm = 2,151 (80% power), 2,879 (90% power)
power.prop.test: 570.5 
Simulated power at n = 571 per arm: 0.801 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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. Multiplicity, Missing Data and Analysis Populations

The registry record lists no reported analyses for the primary outcome and no reported analyses for the posted secondary outcomes. It does not report whether the original analysis plan specified a hierarchy among outcomes, a multiplicity adjustment, or another procedure to control interpretation across multiple tests. The secondary p-values are unadjusted. Without a reported plan, it is not possible to determine whether the posted outcomes were confirmatory, exploratory, or interpreted under a broader testing strategy.

The planning illustrations use a two-sided significance level of 0.05, but that is a stated assumption for those illustrations, not a reported description of the trial’s original statistical plan. The trial’s original significance threshold, primary analysis method, and multiplicity approach are not reported in the registry record. Interim analyses and any associated stopping rules are also not reported in the registry record.

The record does not identify the analysis population for the primary endpoint or secondary outcomes. It does not state whether participants were analyzed according to randomized assignment, treatment received, or another population definition. It also does not describe missing-data handling, withdrawals, exclusions, or the number of participants contributing to each secondary outcome. Overall registry enrollment is 37, while the primary outcome denominators are 22 and 12; reasons for the difference are not reported in the registry record.

These omissions matter because analysis populations and missing-data decisions can affect both the estimate and its uncertainty. General statistical context: an analysis that excludes participants with missing outcomes can differ from one that makes explicit assumptions about those outcomes. No such assumptions or procedures can be attributed to this study from the registry information. Similarly, no adjusted model or covariate set is reported, so the posted primary comparison should be understood as unadjusted rather than as evidence from a reported adjusted analysis.

In general, multiplicity procedures help distinguish a planned primary test from a collection of exploratory comparisons. Their absence from the registry record does not show that no procedure was used; it means the procedure is not reported there. The appropriate interpretation is therefore cautious, especially for the secondary outcomes and any comparison not identified as the primary endpoint.

15. 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 non-serious adverse event terms

For serious adverse events, the registry lists 0 affected participants among 22 at risk in the HTX-011 plus multimodal analgesia group and 0 among 12 at risk in the bupivacaine HCl plus multimodal analgesia group. Deaths are listed as 0 in both groups. The record lists no serious adverse-event terms.

These figures describe what is recorded in this cohort; they do not establish that the underlying risk of a serious event is zero. With limited group sizes, an absence of observed serious events leaves uncertainty about events that could occur in a larger population or over a different follow-up period. The registry lists the primary adverse-event timeframe as through Day 15, but completeness of safety follow-up is not reported in the registry record.

The separate primary outcome counts participants with treatment-emergent adverse events of any reported seriousness category: 18 of 22 in the HTX-011 group and 9 of 12 in the bupivacaine HCl group. Those counts should not be conflated with the serious adverse-event figures. The record also lists other adverse events for 18 and 9 participants, respectively. The available safety summaries do not provide event-level descriptions, severity grades, or causality assessments beyond the categories posted.

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

The primary result describes the observed incidence of treatment-emergent adverse events through Day 15 in two randomized treatment groups that both received oral multimodal analgesia. The observed counts were 18 of 22 for HTX-011 plus multimodal analgesia and 9 of 12 for bupivacaine HCl plus multimodal analgesia. The unadjusted risk difference is -0.068, with an interval that includes zero and extends in both directions. This is an uncertain comparison, not a definitive ranking of the regimens.

The result does not demonstrate that the groups have identical adverse-event incidence. It also does not establish a statistically distinguishable difference. The confidence interval is broad, the outcome denominators are limited, and the registry does not describe the analysis population or missing-data handling. The serious adverse-event counts are zero in both groups, but zero observed events in this cohort do not prove that serious events cannot occur.

The record’s focus on postoperative pain does not make the primary endpoint a pain outcome. The primary measure is safety-related, and the posted secondary measures are pharmacokinetic. Pain intensity, duration of pain, use of rescue medication, and other direct measures of analgesic effect are not reported in the registry record. Consequently, these posted results cannot by themselves establish whether either regimen improves pain or provides a clinically meaningful analgesic benefit.

The pharmacokinetic results describe measured exposure and have their own uncertainties. They do not establish that exposure differences translate into differences in pain or safety. The secondary comparisons are unadjusted, and no multiplicity procedure is reported. They should therefore be treated as descriptive evidence rather than as a basis for a strong confirmatory conclusion.

In general, statistical evidence should be read together with the endpoint definition, comparison design, uncertainty intervals, and completeness of reporting. Here, the most defensible reading is limited to the recorded event counts, the unadjusted contrast, and the range of uncertainty around that contrast. The registry record does not provide enough detail to resolve the uncertainty or support broader clinical claims.

17. Why This Trial Matters Statistically

This cohort illustrates why an observed difference and its precision should be considered together. The primary outcome has group-specific counts and an unadjusted risk-difference estimate, but the confidence interval spans zero and remains broad. A point estimate alone can make a comparison look more conclusive than the underlying data warrant; the interval shows that several directions and magnitudes remain compatible with the posted results.

The active-controlled design also matters for interpretation. Both groups received oral multimodal analgesia, while the assigned local treatment differed in drug and route of administration. The comparison is therefore between complete regimens as described in the record, not between a drug and no treatment. That distinction prevents attributing every observed outcome to the local treatment alone.

The record demonstrates the difference between a safety endpoint and a clinical-effectiveness endpoint. The primary measure counts participants with treatment-emergent adverse events, while the listed secondary measures concern pharmacokinetic exposure. Neither category directly reports pain outcomes. Statistical interpretation must follow the endpoint actually recorded rather than the broader clinical topic named by the study.

Finally, the registry information makes reporting limitations visible. The primary outcome denominators do not match the overall enrollment figure, and the reason is not reported. The analysis population, missing-data methods, and multiplicity plan are also not reported. These details affect how confidently estimates can be evaluated and reproduced. A transparent account of uncertainty and unreported methods is important even when a study is completed and its descriptive results are available.

18. 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 cohort is described as an abdominoplasty group, so the posted results are specific to this surgical cohort. The record does not report enough information to assess how participants were selected or how broadly the cohort represents other surgical populations. Findings from this record should not automatically be generalized to procedures or populations not described in it.

The overall enrollment is 37, while the primary endpoint has denominators of 22 and 12. The registry record does not explain the difference, identify reasons for noncontribution, or describe participant flow. Without those details, it is difficult to judge whether the posted outcome data represent all enrolled participants or whether missing outcome data could influence the comparison.

The primary comparison is unadjusted, and the record does not identify the statistical method used to calculate its interval or p-value. No adjustment variables, subgroup analyses, or sensitivity analyses are reported. The absence of reported analyses also limits assessment of whether assumptions were checked or whether alternative analysis choices were examined.

The follow-up window for the primary outcome is through Day 15. The registry does not provide further detail about follow-up completeness or event ascertainment. The serious adverse-event summaries list no events, but the limited cohort size and defined follow-up period restrict what can be concluded from those counts.

Finally, the registry record does not report direct pain outcomes among the results discussed, the original sample-size justification, or the detailed statistical analysis plan. The planning illustrations are based on observed effects and should not be mistaken for the study’s original design rationale. These reporting limitations constrain interpretation; they do not establish that unreported procedures or outcomes were absent from the conduct of the study.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Cohort 2 (Abdominoplasty) of: A Multi-surgery Assessment of ZYNRELEF (HTX-011) — NCT06109428.
• Registry record last updated 2026-10-28; status last verified 2023-10.
• Results first posted 2026-10-28.
• 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.

22. Record Summary

NCT06109428 is the completed Phase 4, randomized, double-blind, active-controlled, parallel abdominoplasty cohort of a multi-surgery assessment of HTX-011. The study compared HTX-011 400 mg/12 mg via instillation plus oral multimodal analgesia with bupivacaine HCl 125 mg via injection plus oral multimodal analgesia. Enrollment is listed as 37; the primary outcome denominators are 22 and 12.

The primary endpoint was the incidence of treatment-emergent adverse events through Day 15. Counts were 18 of 22 and 9 of 12, respectively. The unadjusted risk difference was -0.068, with a 95% confidence interval from -0.361 to 0.225 and an unadjusted p-value of 0.638. Serious adverse events and deaths were listed as 0 in both groups.

Pharmacokinetic results were posted for Cmax, AUClast, and AUCinf through 144 hours. The registry record lists no reported analyses and does not report the original sample-size justification, analysis population, missing-data methods, or multiplicity plan.