Phase IIIb Study of APD421 in Combination as PONV Prophylaxis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase IIIb Study of APD421 in Combination as PONV Prophylaxis (NCT02337062), a randomized phase 3 study. The primary outcome is Number of Participants With Complete Response.

2. Clinical Question

3. Trial Design

The registry describes a Phase III randomized, parallel-group study of APD421 as combination prophylaxis against PONV. The official title describes the study as double-blind, while the registry masking field records quadruple masking. The record also identifies the study as placebo-controlled. These are design descriptions; they do not, by themselves, establish how masking was maintained in practice.

The treatment groups were APD421 5mg plus a standard anti-emetic and placebo plus a standard anti-emetic. The registry describes a single intravenous dose of APD421 or placebo. It records an enrollment of 1147 and a completed status. The primary completion date is recorded as 2015-09 and the start date as 2015-02.

The primary outcome was the number of participants with complete response in the modified intent-to-treat population. The timeframe was 24 hours after the end of surgery, defined in the outcome description as wound closure. Complete response required both no emesis and no use of rescue medication in that interval.

The registry lists five secondary outcomes: emesis, receipt of rescue medication, any nausea, significant nausea, and time to first violation of PONV criteria. Numerical results are posted for three of these outcomes in the record used for this analysis. Numerical results for significant nausea and time to first violation of criteria for PONV are not reported in the registry record. More detailed information about site locations, the specific standard anti-emetic, and the protocol’s original statistical design assumptions is 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: Modified intent-to-treat

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 Number of Participants With Complete Response, measured over 24 hours after the end of surgery.

The primary endpoint counts participants who had a complete response during the 24 hours after the end of surgery. The endpoint’s definition is a combined criterion: a participant must have had no emesis and must not have used rescue medication during that period. The endpoint description defines the end of surgery as wound closure.

This kind of outcome is useful for representing more than one aspect of postoperative symptom control in a single binary measure. A participant either meets the complete-response definition or does not. The outcome therefore captures both vomiting and the need for additional medication, rather than treating either component alone as sufficient to establish a complete response. It does not indicate how severe or prolonged any nausea was, and those are distinct outcomes listed separately in the registry.

In the posted results, 330 participants in the APD421 group and 268 in the placebo group had a complete response. The corresponding reported response proportions are 0.577 and 0.466. The primary comparison is reported as a risk difference of -0.111, with a confidence interval that does not include zero and a reported p-value of <0.001. The direction of the group results is consistent with a higher complete-response proportion in the APD421 group. The endpoint describes the recorded outcome during a defined postoperative interval; it does not, on its own, answer questions about outcomes beyond that interval or establish the effects of treatment in other populations.

7. Results Posted in the Registry

• Placebo + Standard Anti-emetic: 46.6% (268/575) versus 57.7% (330/572) on control; risk difference -11.1 percentage points (95% CI -16.8 to -5.3), risk ratio 0.81 (0.72–0.90); unadjusted two-proportion z-test p = <0.001.

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.

Number of Participants With Emesis

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Placebo + Standard Anti-emetic: 20.0% (115/575) versus 13.8% (79/572) on control; risk difference 6.2 percentage points (95% CI 1.9 to 10.5), risk ratio 1.45 (1.11–1.88); unadjusted two-proportion z-test p = 0.005.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Placebo + Standard Anti-emetic than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants Receiving Rescue Medication

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Placebo + Standard Anti-emetic: 49.4% (284/575) versus 40.9% (234/572) on control; risk difference 8.5 percentage points (95% CI 2.7 to 14.2), risk ratio 1.21 (1.06–1.37); unadjusted two-proportion z-test p = 0.004.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Placebo + Standard Anti-emetic than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants With Any Nausea

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Placebo + Standard Anti-emetic: 58.3% (335/575) versus 50.0% (286/572) on control; risk difference 8.3 percentage points (95% CI 2.5 to 14.0), risk ratio 1.17 (1.05–1.30); unadjusted two-proportion z-test p = 0.005.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Placebo + Standard Anti-emetic than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The numerical secondary outcomes follow a consistent broad pattern: counts for emesis, use of rescue medication, and any nausea were higher in the placebo plus standard anti-emetic group than in the APD421 plus standard anti-emetic group. Their posted unadjusted comparisons also indicate differences between the groups. This direction is compatible with the primary result, where complete response was more frequent in the APD421 group.

The secondary outcomes measure different aspects of PONV and should not be treated as duplicates of complete response. Emesis and rescue medication are components of the primary endpoint’s definition, while any nausea captures a separate symptom. A difference in any one of these outcomes does not by itself establish the full composite outcome or describe every participant’s symptom experience.

Although the overall direction is coherent, secondary findings carry less weight than the primary comparison. The registry does not report whether a hierarchy or multiplicity adjustment was used. When several outcomes are tested, unadjusted p-values do not account for the increased chance of observing at least one apparently notable result across the set. The secondary results should consequently be read as supporting context, not as independent confirmation with the same status as the designated primary endpoint.

The registry lists significant nausea and time to first violation of PONV criteria as additional secondary outcomes, but numerical results for these outcomes are not reported in the registry record. The secondary evidence is therefore incomplete in the available record, and no conclusion about those outcomes can be drawn from the listed endpoint names alone.

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

• Number of Participants With Emesis
• Number of Participants Receiving Rescue Medication
• Number of Participants With Any Nausea
• Number of Participants With Significant Nausea
• Time to First Violation of Criteria for PONV

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary at the participant level: each participant either met the complete-response definition or did not. The posted arm results are counts of participants with the event, accompanied by the number in each arm. A risk, or proportion, expresses the count with the event relative to the number of participants in that group. The reported primary proportions are 0.577 for APD421 plus standard anti-emetic and 0.466 for placebo plus standard anti-emetic.

What does the risk difference represent?

A risk difference subtracts one group’s event proportion from the other group’s proportion. It is an absolute measure, expressed on the probability scale, rather than a relative comparison. The posted primary risk difference is -0.111. The comparison record labels the other arm as placebo and records the contrast in an order that yields this negative sign. Looking at the arm-level proportions alongside the contrast is important for understanding direction: complete response was more frequent in the APD421 group. The confidence interval for the difference is -0.168 to -0.053.

What does the chi-squared test assess?

The sponsor’s recorded primary analysis is a chi-squared test of superiority. In general, a chi-squared test assesses whether the observed distribution of a categorical outcome across groups is compatible with the null hypothesis of no association between group and outcome. For this binary outcome, it compares the event and non-event pattern across the randomized groups. Its p-value is not the size of the treatment contrast; the risk difference describes the estimated absolute contrast, while the test addresses how compatible the observed data are with the stated null model.

The registry reports p < 0.001 for the primary analysis. The recalculated unadjusted comparison also reports p < 0.001. A p-value is calculated assuming the null hypothesis and the analysis model; it is the probability, under those assumptions, of results at least as incompatible with the null as the observed result. It is not the probability that the treatment has no effect, and it does not convey the practical importance or precision of an estimate on its own.

Why use a confidence interval?

A confidence interval communicates the uncertainty around an estimated contrast. In general, a confidence interval is generated by a method that, under its assumptions, would cover the target value at its stated rate over repeated samples. It gives a range of values compatible with the data and method, rather than a guarantee that the true value lies within this particular interval. For the primary contrast, the posted interval excludes zero, indicating that the interval does not include the no-difference value for a risk difference.

For binary outcomes, the amount of information depends in part on how many participants experience the event and how many are observed in each group. The simple recalculation uses the posted counts and group sizes and is unadjusted. It does not account for covariates or other features not included in the summary data. The registry’s sponsor analysis remains the record of the trial’s own reported analysis; the recalculation is a separate descriptive check based on the posted summaries.

How should secondary tests be understood?

The registry posts chi-squared superiority analyses for the numerical secondary outcomes. The displayed recalculations are unadjusted comparisons. In general, testing multiple outcomes creates more opportunities for at least one nominally small p-value to arise by chance, even if no adjustment is made to any individual test. A multiplicity procedure can address this issue, but the method, if any, is not reported in the registry record. Secondary findings should therefore be regarded as supportive or exploratory rather than as equivalent in evidential status to the primary comparison.

Other details that would help assess the analyses—including the missing-data approach, any covariate adjustment, and the exact handling of analysis populations beyond the primary outcome’s modified intent-to-treat description—are not reported in the registry record. The posted statistics should be read with those omissions in mind.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.111, with a confidence interval from -0.168 to -0.053. The interval does not include zero and lies on the negative side of the contrast as recorded. The arm-level proportions clarify the direction: complete response was recorded more often with APD421 plus standard anti-emetic than with placebo plus standard anti-emetic. The interval conveys uncertainty around the estimated contrast; it does not mean every value in the interval is equally likely, and it does not account for limitations that are not represented in the calculation.

The reported p-value is <0.001. This is compatible with the interval’s exclusion of the no-difference value, because both summaries indicate evidence against a null difference under their respective methods. The p-value is not a measure of the probability that the result occurred by chance, and the confidence interval does not guarantee the result will generalize beyond the trial.

The intervals for the posted secondary risk differences also exclude zero. Their estimates and intervals are unadjusted, and the registry record does not report a multiplicity adjustment. Thus their nominal precision should not be taken as resolving the additional uncertainty associated with examining multiple secondary outcomes.

Precision is also distinct from clinical importance. The record supplies statistical estimates for the measured outcomes, but it does not report a threshold for what would constitute a clinically important difference. The meaning of the primary endpoint is limited to complete response as defined over 24 hours after wound closure. The confidence interval cannot address unmeasured outcomes, missing-data assumptions that are not reported, or applicability to settings and treatment regimens not described in the registry.

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 illustrations based on the observed effect, not the trial’s original sample-size justification. The original design assumptions and justification are not reported in the registry record. The figures are participants per arm for the binary outcomes; they are not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if the effect and model assumptions held. The 90% power column gives the corresponding planning target for a 90% chance. These are design calculations for hypothetical future studies, not observed properties of the completed trial.

Each row changes the effect size used for planning. Planning for 100% of the observed effect uses the full observed effect as the target; planning for 75% or 50% uses a smaller target. Smaller effects are harder to detect with the same design, so they require more participants per arm to reach the same power target. For example, for the primary comparison, the planning figures rise from 318 participants per arm for 80% power at 100% of the observed effect to 1,265 participants per arm for 80% power at 50% of the observed effect. These numbers depend on the stated assumptions and should not be treated as a recommendation or a guaranteed requirement.

This is not observed power. Power is a planning concept defined for a specified effect and assumptions; calculating it after observing the trial’s result does not provide an independent measure of how convincing that result is. The original trial’s sample-size assumptions are not reported in the registry record.

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 = 0.577; treatment proportion p₁ = 0.466; average p̄ = 0.522.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7065 = 1.3846.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.7021 = 0.5909.
4. n = (1.3846 + 0.5909)² / (-0.1108)² = 317.7, rounded up to 318 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 <- 0.576923076923077                          # control proportion
p1 <- 0.466086956521739                          # 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(2337062)
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 = 318 (80% power), 425 (90% power)
 75% of observed effect: n per arm = 564 (80% power), 755 (90% power)
 50% of observed effect: n per arm = 1,265 (80% power), 1,693 (90% power)
power.prop.test: 317.7 
Simulated power at n = 318 per arm: 0.805 (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. Analyses Reported by the Sponsor

The sponsor’s recorded primary analysis is a chi-squared superiority test comparing APD421 plus standard anti-emetic with placebo plus standard anti-emetic. The registry reports p < 0.001. A simple unadjusted recalculation from the posted primary counts gives the same reported p-value threshold and a risk-difference estimate with a confidence interval that excludes zero. The arm-level counts and proportions also point in the same direction, with more complete responses recorded in the APD421 group.

The registry record does not include a sponsor-reported numerical effect estimate or confidence interval for this primary analysis; the recalculated risk difference is therefore a supplementary summary of the posted counts, not a replacement for the sponsor’s analysis. The record indicates no discrepancy between the recalculation and the posted analysis. If a discrepancy were present, the sponsor’s own analysis would take precedence; that is not the situation recorded for this trial.

The recalculation is limited to the available summary statistics. It is unadjusted and does not reproduce any unreported modeling choices, population handling, or other protocol-specific procedures. The chi-squared result should be cited as the registry’s own analysis, while the risk difference and its interval should be understood as a summary recalculated from the posted group data.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and lists secondary outcomes, but a statistical procedure for controlling multiplicity is not reported in the registry record. Multiplicity matters when several hypotheses are tested: even if each test uses a conventional threshold, the chance of at least one nominally positive result across a collection of tests can increase. An adjustment or a prespecified testing hierarchy can address this concern, but the record does not describe whether either was used.

The primary comparison is more clearly designated than the secondary comparisons, which supports treating it as the principal statistical result. The secondary results remain informative descriptions of related outcomes, but their unadjusted p-values should not be interpreted as though they arose from a single isolated test. The registry record does not report a correction that would allow family-wise or other multiplicity-controlled interpretation.

The primary outcome population is identified as modified intent-to-treat. The record does not provide the detailed definition of that population or describe how participants with missing outcome data were handled. Missing-data methods, reasons for missingness, and sensitivity analyses are not reported in the registry record. These omissions limit assessment of whether the recorded outcome counts and comparisons are robust to incomplete outcome data.

The record also does not report a detailed statistical analysis plan, including whether any covariates were used, whether interim analyses were planned or conducted, or the original sample-size justification. These details should not be inferred from the completed status or the posted p-values. The reported results can be described as recorded, while these unreported procedures remain uncertainties in evaluating how the analysis was planned and implemented.

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 5.0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: post procedural haemorrhage (0.3%), peritonitis (0.3%), post operative wound infections (0.3%), small intestinal obstruction (0.3%), wound secretion (0.2%).

The registry reports serious adverse events among 14 participants in each treatment group. The at-risk counts were 572 for APD421 plus standard anti-emetic and 575 for placebo plus standard anti-emetic. It also records other adverse events among 111 participants in the APD421 group and 120 in the placebo group. The record lists 1 death in the APD421 group and 0 in the placebo group.

The serious-event terms listed among the top terms include post procedural haemorrhage, peritonitis, post operative wound infections, and small intestinal obstruction, each recorded as 0.3%; wound secretion and pelvic organ injury are each recorded as 0.2%. These are descriptive registry figures. The record does not establish that a particular event was caused by study treatment, and counts alone do not assess clinical context, timing, severity, or attribution.

These adverse-event data should be read alongside the trial’s scope and reporting. The figures describe the recorded groups and do not establish comparative safety in other populations or treatment settings. Detailed event-level narratives and further assessments are not reported in the registry record.

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

The posted primary results show a higher recorded complete-response proportion in the APD421 plus standard anti-emetic group than in the placebo plus standard anti-emetic group during the 24 hours after surgery. The risk-difference interval excludes zero, and the registry’s chi-squared analysis reports p < 0.001. Together, these statistics describe evidence of a difference in the trial’s primary outcome under the reported analyses.

The result is specific to the complete-response definition: no emesis and no rescue medication during the stated postoperative interval. It does not mean that all participants in the APD421 group had no symptoms, that nausea was absent, or that the same result applies to a different outcome or follow-up period. Separate nausea outcomes are listed, and some secondary results are not reported in the registry record.

Both groups received a standard anti-emetic. The comparison therefore addresses the addition of APD421 versus placebo in that treatment context. It does not estimate the effect of APD421 without background anti-emetic treatment. The identity and regimen of the standard anti-emetic are not reported in the registry record, which limits how specifically the treatment context can be characterized.

The result also does not establish that the observed difference will be reproduced in every clinical setting or patient population. The registry record does not report several details relevant to interpreting transportability and analysis, including the original sample-size justification, detailed eligibility criteria, missing-data methods, and any multiplicity procedure. Statistical significance alone does not determine clinical importance; the record does not report a threshold for a clinically meaningful difference.

Finally, the posted safety counts are descriptive and do not prove that events were or were not caused by treatment. The efficacy comparison and the adverse-event record answer different questions and should be interpreted separately. The appropriate conclusion is limited to what was recorded for this randomized comparison and its specified outcomes.

18. Why This Trial Matters Statistically

This trial illustrates the value of distinguishing an absolute effect estimate from a test result. The primary risk difference describes the contrast in complete-response proportions on an absolute scale, while the chi-squared p-value addresses compatibility with a null hypothesis. The confidence interval adds information about uncertainty around the estimate. These measures complement one another but do not answer the same question.

It also demonstrates why outcome definitions matter. Complete response combines absence of emesis with absence of rescue medication over a defined period. The secondary outcomes separate some of those components and include nausea measures. A coherent direction across related outcomes can help contextualize the primary result, but it does not make each endpoint interchangeable or remove the need to consider multiplicity.

The record provides enough group-level information to describe the primary counts and calculate an unadjusted comparison, while leaving several analytical details unreported. This contrast between available summary results and unavailable planning or missing-data information is important for evidence appraisal: an apparently precise estimate can still be subject to uncertainty about how the analysis population and incomplete outcomes were handled.

Finally, the planning illustrations show how study size depends on the effect a future study aims to detect. Smaller target effects require larger per-arm planning figures under the stated assumptions. Such calculations support design discussions, but they are not observed power and do not explain the original design of this completed trial, whose sample-size justification is not reported in the registry record.

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.

The registry record leaves important details unavailable for independent appraisal. The specific standard anti-emetic and its regimen are not reported, so the background treatment context cannot be described beyond its use in both groups. Detailed eligibility criteria and further population characteristics are also not reported in the registry record.

The primary outcome population is called modified intent-to-treat, but the definition of that population is not reported. The record does not describe missing-data handling, reasons for missing outcomes, or sensitivity analyses. Consequently, the effect of incomplete outcome data on the posted counts cannot be assessed from the registry information.

The record does not report the original sample-size justification, the detailed statistical analysis plan, or whether any interim analyses took place. It also does not report a multiplicity procedure for the secondary outcomes. These omissions limit assessment of how design and analysis choices were prespecified and how the secondary p-values should be interpreted collectively.

Only three secondary outcomes have numerical results in the record used for this analysis. Results for significant nausea and time to first violation of PONV criteria are not reported in the registry record. The safety information is also presented as summary counts and selected event terms, without detailed event narratives or attribution information.

These limitations do not change the recorded counts or the arithmetic of the unadjusted comparison, but they restrict the conclusions that can be drawn about robustness, clinical context, and generalizability. The findings should remain tied to the recorded study population, background treatment, endpoint definition, and follow-up interval.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Phase IIIb Study of APD421 in Combination as PONV Prophylaxis — NCT02337062.
• Registry record last updated 2019-03-20; status last verified 2019-03.
• Results first posted 2017-08-04.
• 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

The registry record describes a completed, randomized, parallel-group Phase III study of APD421 plus standard anti-emetic versus placebo plus standard anti-emetic in high-risk patients undergoing surgery. It records quadruple masking and an enrollment of 1147. The primary endpoint was complete response, defined as no emesis and no rescue medication in the 24 hours after wound closure.

The posted primary counts were 330 of 572 in the APD421 group and 268 of 575 in the placebo group. The registry reports a chi-squared superiority analysis with p < 0.001. The unadjusted risk-difference recalculation is consistent with the recorded direction and significance. Numerical secondary results are available for emesis, rescue medication, and any nausea; other listed secondary results are not reported in the registry record.

Important details, including the original sample-size justification, missing-data methods, and multiplicity procedure, are not reported in the registry record. The results therefore support interpretation of the specified outcomes in this trial, with those reporting limitations kept in view.