Evaluation of N1539 Following Bunionectomy Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of N1539 Following Bunionectomy Surgery (NCT02675907), a randomized phase 3 study. The primary outcome is Summed Pain Intensity Difference Over the First 48 Hours (SPID48).

2. Clinical Question

The clinical question concerns acute postoperative pain following a specific surgery, not pain in every setting or pain over a longer period. Random assignment supports a comparison of the two assigned groups, while the placebo comparator helps distinguish the groups’ outcome patterns within this trial. The endpoint captures pain intensity over the first 48 hours rather than relying on a single assessment. Secondary outcomes included measures of rescue analgesia use and pain relief, along with thresholds for improvement at specified time points. Those outcomes add context to the primary measure, but they do not replace it. The registry record does not report further details about eligibility criteria, the clinical threshold for a meaningful difference in SPID48, or how missing observations were handled.

3. Trial Design

This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of N1539 following bunionectomy. The registry lists quadruple masking. Enrollment was 201, and the record lists the study as completed. The recorded start was 2016-01 and primary completion was 2016-07. Baudax Bio is listed as the sponsor.

The two groups received N1539 30 mg or intravenous placebo. Each was administered every 24 hours for up to 3 doses. The primary objective was to evaluate the analgesic efficacy of N1539 in people with acute moderate to severe pain following unilateral bunionectomy. The primary outcome was assessed over 48 Hours in the Intent-to-Treat (ITT) population.

Randomization is intended to make treatment assignment independent of participant characteristics on average, reducing systematic selection into the groups. Blinding is intended to limit the influence of treatment expectations on care, participant reports, and outcome assessment. The parallel design means that the assigned groups were compared over the study period rather than participants crossing between treatments. These design features support interpretation of the between-group comparison, but do not by themselves establish that every possible source of bias was avoided.

The registry record does not report the original sample-size justification, detailed randomization procedures, the exact roles covered by quadruple masking, or the statistical analysis plan. It also does not report whether interim analyses were planned or conducted. The listed enrollment and design features describe the trial framework, but cannot fill in those missing protocol details.

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.

Treatment Phase (48 Hours Post-Dose 1)

Reasons for not completing this period:

Study Overall

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) population

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 Summed Pain Intensity Difference Over the First 48 Hours (SPID48), measured over 48 Hours.

SPID48 combines repeated pain intensity assessments into a time-weighted measure over the first 48 hours after Dose 1. Pain intensity was recorded on a Numeric Pain Rating Scale ranging from 0, no pain, to 10, the worst pain imaginable. Assessments were scheduled at 0.25, 0.5, 0.75, 1, and 2 hours after Dose 1, then every 2 hours until 48 hours. At each time point, the difference from baseline was calculated. Each difference was weighted by the time elapsed since the previous observation, and the weighted values were summed.

The endpoint is useful for representing the pattern of pain intensity across the assessment period rather than treating one observation as the whole experience. Time weighting accounts for the interval represented by each observation in the sum. The registry specifies that a smaller SPID value, meaning a more negative value, was better. The reported group summaries are least-squares means with standard errors, so they are model-based mean estimates accompanied by a measure of their statistical uncertainty.

Interpretation depends on the endpoint’s construction and direction: a more negative group mean indicates a more favorable SPID48 result under the registry’s definition. The registry record does not report a threshold defining a clinically important difference for this measure. Consequently, statistical evidence of a group difference should not by itself be treated as proof of a particular degree of clinical importance.

7. Results Posted in the Registry

• N1539 30 mg: mean -6,956 versus -4,829 on control; difference -2,127 (95% CI -3,570 to -683.62), standardized effect d = -0.41; z-test p = 0.004.

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.

Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 6

• 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:
  • N1539 30 mg: 32.0% (32/100) versus 19.8% (20/101) on control; risk difference 12.2 percentage points (95% CI 0.2 to 24.2), risk ratio 1.62 (0.99–2.63); unadjusted two-proportion z-test p = 0.048.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for N1539 30 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 24

• 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:
  • N1539 30 mg: 37.0% (37/100) versus 20.8% (21/101) on control; risk difference 16.2 percentage points (95% CI 3.9 to 28.5), risk ratio 1.78 (1.12–2.81); unadjusted two-proportion z-test p = 0.011.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for N1539 30 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 6

• 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:
  • N1539 30 mg: 16.0% (16/100) versus 7.9% (8/101) on control; risk difference 8.1 percentage points (95% CI -0.8 to 17.0), risk ratio 2.02 (0.91–4.51); unadjusted two-proportion z-test p = 0.077.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between N1539 30 mg and the control. The interval gives the range of effects that remain compatible with the data.

The selected secondary results broadly point in the same direction as the primary SPID48 comparison for the 30% improvement thresholds: more participants in the N1539 group met that threshold at the reported assessment times. The result for the 50% improvement threshold at Hour 6 is less conclusive, with an interval that crosses zero. Taken together, the secondary outcomes provide some additional context about threshold improvement, but they do not establish that every measure of pain response differed between groups.

These outcomes complement the primary measure because they express improvement as a participant-level threshold rather than a time-weighted summary of repeated pain scores. Other listed secondary outcomes included rescue analgesia use and time to pain relief. The registry record lists those outcomes but the numeric results summarized for this analysis do not include their estimates. It also lists additional outcome measures and analyses, so the selected results should not be mistaken for a complete account of all secondary findings.

There were multiple secondary outcomes, thresholds, and time points. If many comparisons are examined, some may appear more persuasive by chance, even when the underlying effects are limited. The registry record does not report whether the secondary analyses were adjusted for multiplicity, how they were ordered, or whether they were designated confirmatory or exploratory. Their unadjusted results therefore carry less weight than the primary outcome and should be treated as supportive rather than as independent confirmation of efficacy.

The pattern is not a direct replication of the primary analysis: each secondary outcome uses a different definition and analysis method. Differences in threshold, timing, or endpoint construction can lead to different estimates. The overall direction is informative, but no single secondary result should be used to replace the primary endpoint or to infer unreported outcomes.

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

• Summed Pain Intensity Difference (SPID) at Other Intervals
• Time to First Dose of Rescue Analgesia
• Number of Subjects Utilizing Rescue Analgesia
• Number of Doses of Rescue Analgesia Utilized Per Subject
• Time to Perceptible Pain Relief (TTPPR)
• Time to Meaningful Pain Relief (TTMPR)
• Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 6
• Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 24

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical measure formed from repeated pain intensity observations. The registry reports least-squares means and standard errors for the two groups. A mean describes the central level of the measured outcome, while a standard error indicates the uncertainty in the estimated group mean. It does not describe how much individual pain responses varied. The registry record does not give a standard deviation for the primary outcome.

How to read the group contrast

The mean difference is expressed as N1539 minus placebo. Its estimate is -2127.0. For this endpoint, a more negative SPID value is better, so a negative contrast is in the direction of a lower, more favorable SPID48 in the N1539 group. The interval extends from -3570.0 to -683.6. An interval summarizes uncertainty around an estimated contrast; values nearer the ends represent less and more favorable contrasts compatible with the analysis, subject to the method and assumptions used. The confidence level is not reported in the registry record.

The reported group means are least-squares means. In general, least-squares means are estimated group averages from a statistical model and can differ from simple arithmetic averages when the model includes covariates or other terms. The registry record does not specify the model terms used for these means, so the exact adjustment structure is not reported. The recalculated comparison is an unadjusted calculation from the posted summary statistics.

What the p-values convey

A p-value describes how incompatible the observed data are with a specified null hypothesis under the analysis assumptions. It does not measure the probability that the null hypothesis is true, the probability that results are due to chance, or the size or importance of an effect. For the primary endpoint, the recalculated unadjusted p-value is 0.004; the sponsor-reported two-sided t-test p-value is 0.003. The two values are similar, and both accompany a result in the direction favoring the lower SPID48 mean. The registry’s reported analysis takes precedence as the trial’s own analysis.

The p-value should be considered alongside the estimated difference and interval. A small p-value alone does not describe how large or precise a contrast is. Conversely, an interval describes a range of uncertainty but does not establish whether the differences within that range matter clinically. The registry record does not state a clinical-importance threshold for SPID48.

Why repeated observations matter

SPID48 summarizes repeated observations rather than a single pain rating. The registry’s time-weighting method multiplies each pain intensity difference from baseline by the elapsed time since the preceding observation, then sums the weighted values. This construction makes the timing of assessments part of the endpoint. It also means the resulting units are not the same as a single rating on the 0-10 pain scale. A reader should not interpret -6956.0 as a pain score on that scale.

Repeated measures can provide a broader account of the outcome pattern, but interpretation depends on how the scores and assessment times are handled. The registry describes the planned assessment schedule and calculation, but the record summarized for these results does not report details on departures from the schedule, missing observations, or sensitivity analyses.

Binary secondary outcomes

Some secondary outcomes count participants who reached an improvement threshold by a stated time. A risk difference compares the proportions in the groups by subtracting the placebo proportion from the N1539 proportion. Positive estimates indicate a greater observed proportion in the N1539 group. The interval for the Hour 6 30% improvement risk difference runs from 0.002 to 0.242, and its recalculated p-value is 0.048. The sponsor-reported Cochran-Mantel-Haenszel p-value is 0.045.

At Hour 24 for 30% improvement, the risk difference estimate is 0.162, with an interval from 0.039 to 0.285. The recalculated p-value is 0.011, and the sponsor-reported Cochran-Mantel-Haenszel p-value is 0.011. For 50% improvement at Hour 6, the risk difference estimate is 0.081, with an interval from -0.008 to 0.170; the recalculated p-value is 0.077 and the sponsor-reported value is 0.078. These estimates concern different thresholds and time points, and should not be treated as interchangeable measures.

For binary outcomes, a confidence interval that includes zero is compatible with no difference in proportions under the interval’s method. An interval that does not include zero indicates a more clearly directional estimate under that method, but does not resolve multiplicity or clinical importance. These general interpretations do not substitute for the trial’s planned analysis, whose full specification is not reported in the registry record.

Over-dispersion and model assumptions

In general, over-dispersion occurs when binary or count data vary more than a statistical model assumes. If it is not accounted for when present, standard errors can be too small and intervals too narrow. This is a general consideration, not a reported finding about this trial. The registry record does not report an over-dispersion assessment or enough model detail to determine whether it was relevant to the reported secondary analyses.

11. Confidence Intervals and Precision

The primary mean difference estimate is -2127.0, with an interval from -3570.0 to -683.6. The interval lies on the negative side of zero, matching the direction of the lower N1539 SPID48 mean and the registry’s definition that more negative values are better. Its width indicates that the data are compatible with a range of possible group differences, rather than fixing the true contrast at the point estimate. The confidence level and interval-construction method are not reported in the registry record.

The standard errors for the group means are 521.7 for N1539 and 519.6 for placebo. These quantify uncertainty around the estimated means, not the range of individual outcomes. The comparison interval is more directly relevant to the uncertainty in the between-group contrast. It should not be read as an interval containing most participants’ pain results.

For the binary secondary outcomes, the Hour 6 30% improvement risk difference interval is 0.002 to 0.242, and the Hour 24 interval is 0.039 to 0.285. The Hour 6 50% improvement interval is -0.008 to 0.170 and spans zero. That interval is compatible with both a small difference in either direction under its method. These intervals concern different outcomes and cannot be used as precision estimates for SPID48.

Precision and clinical importance are separate questions. A narrow interval can still describe an effect of limited clinical value, while a broader interval can leave substantial uncertainty about the effect. The registry record does not provide a clinically important difference threshold for the primary endpoint, nor does it report the confidence level for the intervals. The estimates therefore support interpretation of direction and uncertainty, but do not alone determine 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 are planning calculations based on the observed effect, not the trial’s original design justification. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect. The figures are participants per arm for these continuous and binary outcomes; they are not total event counts. Time-to-event calculations, if present, would instead be expressed as total events, but the outcomes are not time-to-event planning rows.

The column for 80% power gives the illustrative participants per arm for a future study to have an 80% chance of detecting the specified effect under the planning assumptions, if that effect and assumptions are correct. The 90% power column gives the corresponding planning figure for a higher chance of detection. These are prospective design illustrations, not descriptions of the completed trial’s achieved power.

Rows planning for 100% of the observed effect use the observed estimate as the target; rows planning for 75% or 50% use smaller target effects. Smaller effects need more participants to detect reliably, which is why the illustrations increase as the assumed fraction decreases. For the primary outcome, the listed participants per arm are 95 and 127 when planning for 100% of the observed effect, 169 and 226 for 75%, and 379 and 507 for 50%, for 80% and 90% power respectively.

These figures are sensitive to the observed effect and the assumptions used. In particular, an observed effect from a completed trial may not be a stable estimate of the effect expected in a future study. The original trial’s sample-size assumptions and justification are not reported in the registry record. This is not observed power; the figures are planning illustrations rather than a retrospective measure of the trial’s ability to detect its result.

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 = -2126.700; pooled standard deviation σ = 5219.219.
2. n = 2 × (1.96 + 0.842)² × 5219.219² / -2126.700² = 94.5, rounded up to 95 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 <- -2126.7                      # observed difference in means
sigma <- 5219.21878997597                     # 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(2675907)
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 = 95 (80% power), 127 (90% power)
 75% of observed effect: n per arm = 169 (80% power), 226 (90% power)
 50% of observed effect: n per arm = 379 (80% power), 507 (90% power)
power.t.test: 95.5 
Simulated power at n = 95 per arm: 0.802 (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 sponsor-reported primary analysis is a two-sided t-test, with p = 0.003 and a superiority classification. The unadjusted recalculation from posted summary statistics gives a mean difference of -2127.0, an interval from -3570.0 to -683.6, and p = 0.004. Both comparisons are consistent in direction with the reported group means: SPID48 was more negative in the N1539 group, and more negative values were defined as better.

The recalculated result is a simple unadjusted analysis based on summary statistics. It is useful as a transparent cross-check, but it is not the sponsor’s analysis and does not reproduce any model adjustments that may have been part of the trial analysis. The registry record does not provide enough detail to reconstruct the full analysis model. The two p-values are close, and the registry does not flag a discrepancy between the analyses.

For the selected binary secondary outcomes, the sponsor-reported Cochran-Mantel-Haenszel p-values are 0.045 for 30% improvement at Hour 6, 0.011 for 30% improvement at Hour 24, and 0.078 for 50% improvement at Hour 6. The corresponding recalculated p-values are 0.048, 0.011, and 0.077. These comparisons are not a substitute for the sponsor’s analysis, and their interpretation remains limited by the unreported multiplicity approach and full statistical plan.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists 13 outcome measures and 21 analyses. Multiple outcomes and comparisons create a multiplicity concern: when many hypotheses are assessed, the chance of at least one apparently positive result can increase. Statistical adjustment or a prespecified testing sequence can address this concern, but the registry record does not report a multiplicity procedure, a hierarchy of endpoints, or which secondary comparisons were intended to support formal claims. The secondary p-values should therefore be interpreted cautiously, especially when considered separately from the primary result.

The primary outcome population is identified as the Intent-to-Treat (ITT) population. In general, an ITT analysis compares participants according to their randomized assignment, helping preserve the benefits of randomization. The registry record does not report the detailed population rules, including how participants with unavailable measurements or protocol deviations were handled. The analysis population used for the secondary outcomes is not reported in the registry record.

Missing data handling is not reported in the registry record. This matters because SPID48 depends on repeated pain assessments, and missing observations can affect the time-weighted sum. The record does not specify imputation, assumptions about missingness, sensitivity analyses, or the number of participants contributing to each endpoint at each assessment. It is therefore not possible to assess from these details whether missingness could have influenced the estimates.

The registry record also does not report interim analyses, stopping rules, or the original statistical plan. These omissions do not establish that such procedures were absent; they mean that they are not reported in the registry record. The posted results can be interpreted as recorded, but the unreported analysis details limit independent evaluation of prespecification, missing-data robustness, and control of false-positive findings across outcomes.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sudden death (1.0%), fracture (1.0%).

The registry reports serious adverse events affecting 0 of 100 participants in the N1539 30 mg group and 2 of 101 in the IV Placebo group. Deaths were recorded for 0 participants in the N1539 group and 1 participant in the placebo group. The listed serious-event terms include Sudden death and Fracture, each reported as 1.0%. The record does not provide further event-level details in the information, so the terms should not be assigned to a particular group unless the registry specifies that attribution.

These are counts recorded during the study, not estimates of comparative risk with a complete account of event timing, severity, relatedness, or follow-up. Small counts can leave substantial uncertainty about differences between groups. They also cannot establish that a serious event was caused by or unrelated to a study treatment. The registry record does not report additional details needed to evaluate those questions.

The other adverse event counts were 44 in the N1539 group and 54 in the placebo group, with participants at risk reported as 100 and 101 respectively. These counts do not by themselves summarize event severity or clinical significance. Safety interpretation should remain limited to the adverse event information recorded in the registry.

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

The primary result shows a more negative mean SPID48 in the N1539 group than in the placebo group, consistent with the registry’s definition of a better result. The estimated difference and its interval indicate evidence of a between-group difference in this measure, and the sponsor-reported analysis is aligned in direction with the unadjusted recalculation. Selected secondary threshold outcomes also show a broadly similar direction, although not all are equally conclusive.

These findings do not establish the size of an effect that an individual participant would experience. Group averages and threshold counts describe patterns across study groups; they do not predict an individual response. Nor does a statistical difference by itself establish that the difference is clinically important. The registry record does not report a threshold for a clinically meaningful SPID48 difference.

The results apply to the trial setting: acute moderate to severe pain following unilateral bunionectomy, with the specified intravenous regimens and assessment period. They do not directly answer questions about other operations, pain conditions, dosing schedules, or longer periods. The registry record’s missing details on eligibility, missing data, and the full statistical plan further limit how broadly the results can be interpreted.

The adverse event counts are a separate part of the evidence and should not be collapsed into the efficacy conclusion. The registry reports serious events and deaths by group, but the summarized information does not establish causation or provide a complete safety assessment. A careful interpretation keeps the primary efficacy estimate, secondary outcomes, uncertainty, and safety counts distinct.

18. Why This Trial Matters Statistically

This trial offers a clear example of how a continuous primary endpoint can be built from repeated patient-reported measurements. SPID48 does not use a single pain rating; it combines differences from baseline across time and weights them according to the intervals between observations. That makes endpoint construction central to interpretation. The direction is also explicit: more negative values are better, so the sign of the estimated difference must be read with that definition in mind.

The comparison illustrates why estimates, intervals, and p-values should be read together. The group means and mean difference communicate direction and magnitude in the endpoint’s units; the interval conveys uncertainty; and the p-value summarizes compatibility with a null hypothesis under an analysis. None of those quantities alone answers whether the effect is important to patients. The registry does not supply a clinical-importance threshold, leaving that judgment unresolved by the posted statistics.

The trial also highlights the distinction between a sponsor-reported analysis and an unadjusted recalculation. Their primary results are close and point in the same direction, while the recalculation remains a cross-check rather than a substitute for the trial analysis. Finally, several secondary outcomes create a multiplicity issue, and the registry does not report how it was addressed. This is why statistical evidence across endpoints needs to be interpreted in the context of prespecification, analysis populations, and missing-data methods, details that are 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 does not report the detailed eligibility criteria, limiting assessment of how closely the enrolled population reflects other groups undergoing bunionectomy. The primary outcome uses repeated pain ratings, but missing-data handling and the number of observations contributing to the calculation are not reported. This leaves uncertainty about the influence of unavailable or out-of-schedule assessments on the time-weighted endpoint.

The full statistical model for the least-squares means is not reported, nor are the confidence level and construction method for the intervals summarized in this analysis. The original sample-size justification is also not reported. Consequently, the planning illustrations based on observed effects should not be treated as a description of the trial’s original design choices.

Multiplicity handling across the many outcome measures and analyses is not reported. The clinical importance threshold for SPID48 is also absent, so the statistical result cannot by itself determine the practical significance of the estimated difference. Secondary results are available for only selected outcomes in the summary, while the registry lists additional outcomes whose numerical findings are not included in the registry record described for this analysis.

The safety information is limited to the reported counts and event terms. Further details about timing, seriousness criteria, relatedness, duration, and follow-up are not reported in the registry record. These limitations constrain interpretation but do not demonstrate that the missing procedures or information were absent from the full study record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Evaluation of N1539 Following Bunionectomy Surgery — NCT02675907.
• Registry record last updated 2017-11-17; status last verified 2017-10.
• Results first posted 2017-09-29.
• 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

NCT02675907 is a completed Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group evaluation of N1539 following bunionectomy. The record lists enrollment of 201, quadruple masking, and Baudax Bio as sponsor. The recorded study start was 2016-01 and primary completion was 2016-07.

The primary endpoint was SPID48 in the ITT population. The N1539 group had a least-squares mean of -6956.0, compared with -4829.0 for placebo; more negative values were defined as better. The unadjusted recalculated mean difference was -2127.0, with an interval from -3570.0 to -683.6 and p = 0.004. The sponsor-reported two-sided t-test gave p = 0.003.

Selected secondary findings provide additional but multiplicity-sensitive context. The registry also reports serious adverse events in both groups and one death in the placebo group. Details about missing-data procedures, multiplicity, the original sample-size justification, and the full statistical plan are not reported in the registry record.