Evaluation of Efficacy and Safety of Suzetrigine for Acute Pain After an Abdominoplasty: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Efficacy and Safety of Suzetrigine for Acute Pain After an Abdominoplasty (NCT05558410), a randomized phase 3 study. The primary outcome is Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to Placebo.

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, quadruple-masked, parallel-group study of suzetrigine for acute pain after abdominoplasty. It was placebo-controlled and also included HB/APAP as an active treatment. The registry record lists 1118 participants enrolled and marks the trial completed. The study started on 2022-10-10, and primary completion was 2023-08-25.

The registry descriptions state that suzetrigine was given for 48 hours, beginning with 100 mg and followed by 50 mg every 12 hours. HB/APAP was described as hydrocodone bitartrate 5 mg/acetaminophen 325 mg every 6 hours for 48 hours. Participants in the placebo group received placebo matched to suzetrigine and HB/APAP. The exact allocation proportions and the details of how masking was maintained are not reported in the registry record.

The primary endpoint compared suzetrigine with placebo in the full analysis set, defined as randomized participants who received at least 1 dose of study drug. The registry reports 223 participants in the placebo outcome group and 447 in the suzetrigine outcome group for this endpoint. The record's safety groups have different denominators: 222 for placebo and 448 each for HB/APAP and suzetrigine in the listed safety summaries. These endpoint-specific counts should not be treated as interchangeable.

The record lists additional outcomes involving pain scores, time to pain reduction, patient global assessment, rescue medication, and nausea or vomiting. Numerical results are posted for some, but not all, listed secondary outcomes. The protocol's original sample-size justification, planned allocation ratio, details of interim analyses, and full statistical analysis plan 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:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of the study drug.

6. Primary Endpoint

The registry lists the primary outcome as Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to Placebo, measured over 0 to 48 hours After First Dose of Study Drug.

The primary endpoint was the time-weighted sum of pain-intensity differences, or SPID48, from 0 to 48 hours after the first dose of study drug. Pain intensity was rated on a numeric scale from 0, no pain, to 10, worst possible pain. At each post-dose assessment, pain-intensity difference was calculated by subtracting the baseline score from the later score. Those differences were weighted by the elapsed time since the previous measurement and summed across the 48-hour period.

The registry defines a possible score range from -480, the worst score, to 480, the best score. Positive differences from baseline contribute in the direction of a better score under this definition. A time-weighted summary uses both the size and duration of changes during the assessment window, rather than relying on a single pain rating. It is therefore intended to describe the accumulated pain-intensity difference over the stated period.

The primary results are reported as least-squares means with standard errors. Least-squares means are model-based group means; the registry names ANCOVA as the sponsor's analysis method. The registry record does not report the covariates included in that model, so its adjustment details cannot be described. The primary question is a comparison of group-level endpoint scores; it does not by itself describe every participant's experience or establish how scores changed at each individual assessment time.

7. Results Posted in the Registry

• Suzetrigine (SUZ): mean 118.40 versus 70.10 on control; difference 48.30 (95% CI 33.67 to 62.93), standardized effect d = 0.53; 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.

Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to HB/APAP

• 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 errors.
• Result:
  • Suzetrigine (SUZ): mean 118.40 versus 111.80 on control; difference 6.60 (95% CI -5.32 to 18.52), standardized effect d = 0.07; z-test p = 0.278.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Suzetrigine (SUZ) and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Suzetrigine (SUZ): 67.8% (303/447) versus 49.8% (111/223) on control; risk difference 18.0 percentage points (95% CI 10.1 to 25.9), risk ratio 1.36 (1.18–1.58); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Suzetrigine (SUZ) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Suzetrigine (SUZ): 20.3% (91/448) versus 33.5% (150/448) on control; risk difference -13.2 percentage points (95% CI -18.9 to -7.4), risk ratio 0.61 (0.48–0.76); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Suzetrigine (SUZ) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes span several kinds of questions: accumulated pain scores, time to a specified pain reduction, overall patient assessment, rescue medication use, and nausea or vomiting. They do not all measure the same construct or use the same time window. This breadth can complement the primary endpoint by showing whether conclusions are consistent across related but distinct measures, while also making it important not to treat every endpoint as a direct replication of SPID48.

Numerical results are posted for a subset of the secondary outcomes. They include SPID48 comparing suzetrigine with HB/APAP, the proportion reporting good or excellent on the Patient Global Assessment at 48 hours, and nausea or vomiting from baseline up to Day 19. The results do not all point to a single interchangeable outcome: the active-treatment score comparison is not statistically significant by its posted test, while the patient assessment and nausea-or-vomiting comparisons have reported tests below 0.001. These outcomes differ in comparator, measurement, and timing, so each needs its own interpretation.

The registry lists additional secondary outcomes, including time to pain reduction, SPID24, and rescue medication outcomes. Numerical results for all listed outcomes are not reported in the registry record details used for this account. The absence of posted results for a listed measure should not be interpreted as a null result.

Multiple secondary tests create a multiplicity concern: as more hypotheses are tested, the chance of at least one apparently notable result can increase. The record does not report a multiplicity adjustment or a hierarchy governing secondary testing. Accordingly, unadjusted secondary p-values carry less confirmatory weight than a result from a prespecified, multiplicity-controlled analysis. These findings can be read as supportive or exploratory evidence, but should not independently replace the primary result or be treated as definitive evidence across all secondary outcomes.

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

• Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to HB/APAP
• Time to Greater Than or Equal to (≥) 2-point Reduction in NPRS, SUZ Compared to Placebo
• Time to ≥1-point Reduction in NPRS, SUZ Compared to Placebo
• Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo
• Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP
• Time-weighted SPID as Recorded on the NPRS From 0 to 24 Hours (SPID24), SUZ Compared to Placebo
• Time to First Use of Rescue Medication, SUZ Compared to Placebo
• Percentage of Participants Using Rescue Medication From 0 to 48 Hours, SUZ Compared to Placebo

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it is a numerical score whose values can vary across a scale. The registry reports group least-squares means and standard errors, then gives a mean difference between suzetrigine and placebo. A difference of means is expressed in the endpoint's own units, which are units on a scale. It describes the estimated separation between group averages, not the spread of individual participant scores.

What does an ANCOVA comparison do?

ANCOVA is a model-based method for comparing group outcomes while accounting for covariates included in the model. The registry identifies ANCOVA as the sponsor's primary comparison method and reports a superiority analysis. The covariates, model specification, and handling of any model assumptions are not reported in the registry record. It is therefore not possible to say which characteristics, if any, were included in the adjustment, or how much the adjustment affected the estimate.

The posted least-squares means are model-based rather than simple arithmetic averages. The standard error describes the estimated uncertainty of a mean, under the model and analysis used. It is not a standard deviation of participant scores. A standard deviation describes participant-to-participant variation; a standard error describes uncertainty in an estimated quantity. The posted primary standard errors are 6.1 for placebo and 4.3 for suzetrigine.

How should the mean difference and p-value be read?

The reported mean difference is 48.3, with a confidence interval from 33.67 to 62.93. The sponsor's ANCOVA result is reported as a superiority analysis with p < 0.001. In general, a p-value summarizes how compatible the observed data are with a specified null hypothesis under the analysis assumptions. It is not the probability that the null hypothesis is true, nor a measure of the size or practical importance of a difference. The registry does not report the full test specification beyond ANCOVA and superiority.

A separate simple recalculation uses the posted summary statistics to estimate an unadjusted difference and interval. The recalculation notes that the standard deviations are approximated from the reported standard errors and group sizes. It is therefore a summary-statistic reconstruction, not a rerun of the sponsor's participant-level ANCOVA. The sponsor's own analysis is the trial's reported inferential analysis; the recalculation can help readers see how the posted group summaries relate to the contrast, but it has different assumptions.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model expects. For count or binary outcomes, a model that assumes too little variability can produce standard errors that are too small and confidence intervals that are too narrow. This is a general statistical consideration, not a reported finding about the primary continuous SPID48 endpoint. The registry entries do not report an over-dispersion assessment for the primary analysis, so no conclusion about its presence or absence can be made.

For the posted binary outcomes, group percentages describe the fraction of participants meeting the specified outcome. A risk difference expresses the contrast between those fractions on an absolute scale. For example, the secondary patient global assessment is reported as a risk difference with a confidence interval. The registry names a Cochran-Mantel-Haenszel method for that comparison. For nausea or vomiting, it names Pearson's chi-squared test. These are distinct methods for comparing categorical outcome distributions; the record does not report adjustment details or stratification factors for the former.

What does the active-treatment comparison add?

The secondary comparison of SPID48 between suzetrigine and HB/APAP reports group means, a mean difference, and an ANCOVA test. Its confidence interval ranges from -5.319 to 18.52, and the unadjusted recalculation reports p = 0.278. In general, a confidence interval spanning zero is compatible with both a negative and a positive difference under the method used; it does not establish equivalence. The registry does not report an equivalence or non-inferiority margin, so the result should not be interpreted as proof that the treatments are equivalent.

Effect estimates and p-values answer different statistical questions. The estimate describes the direction and size of a contrast, while an interval expresses its precision under the analysis assumptions. A p-value evaluates compatibility with a null value under a specified test. None of these quantities alone establishes clinical importance, causal mechanism, or applicability outside the trial population and observation period.

The full protocol and detailed analysis plan are not reported in the registry record. Consequently, important operational details—including covariate selection, assumptions checks, missing-data methods, multiplicity control, and any planned sensitivity analyses—cannot be inferred from the named methods alone. Statistical interpretation should distinguish what the registry explicitly reports from general properties of the methods.

11. Confidence Intervals and Precision

The primary mean difference is 48.3 units, and its 95% confidence interval extends from 33.67 to 62.93. In general, a confidence interval gives a range of values compatible with the data and the analysis procedure at the stated confidence level. It represents uncertainty about the estimated group contrast, not the range of individual participant responses and not a guarantee that the true value lies within the observed limits.

Both endpoints of the primary interval are above zero, so the interval supports a positive average contrast under the reported direction of subtraction. This is consistent with the registry's reported superiority result. The interval also conveys the range of magnitudes that remain compatible with the analysis. The point estimate alone would conceal that uncertainty; the interval gives readers more information about precision.

Precision depends on factors such as the amount of information in the comparison, outcome variability, and the analysis method. The primary group sizes differ, and the registry reports standard errors alongside the least-squares means. The registry entries do not include the participant-level data or the model details needed to independently assess all sources of uncertainty. The confidence interval should therefore be read as the interval attached to the posted analysis, not as an independently verified model result.

The active-treatment SPID48 comparison has a confidence interval from -5.319 to 18.52. It includes zero, and the posted unadjusted p-value is 0.278. This indicates less precise evidence about the direction of the mean difference than the primary placebo comparison. It does not demonstrate that the treatments have identical effects. A claim of equivalence would require a prespecified margin and an appropriate analysis; such a margin is not reported in the registry record.

Confidence intervals for the binary secondary outcomes are expressed on the risk-difference scale in the posted comparisons. Their interpretation is distinct from a mean-difference interval, even though both quantify uncertainty about a contrast. The listed secondary interval for patient global assessment is 0.102 to 0.259; for nausea or vomiting it is -0.189 to -0.074. These estimates apply to their respective endpoints and comparison groups, not to the primary SPID48 result.

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 estimates are planning illustrations based on observed effects, not the original design calculation. For continuous and binary outcomes, the entries are participants per arm, not total participants. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario uses the stated fraction of the observed effect as the effect to detect. The registry's original sample-size assumptions and justification are not reported.

The 80% power column gives the illustrative participants per arm for a design with an 80% chance of detecting the selected effect under those assumptions, if that effect is real and the model assumptions hold. The 90% power column gives the corresponding per-arm planning figure for a 90% chance. These are prospective design calculations; they are not observed power and do not describe the probability that the trial's result is true.

The rows that plan for a smaller fraction of the observed effect require more participants per arm. For example, the primary comparison's illustration gives 56 participants per arm for 80% power when planning for 100% of the observed effect, and 223 per arm when planning for 50% of that effect. These values should not be treated as the trial's actual planned sample size or as evidence that the trial was designed around the observed effect.

The stated assumptions also indicate that time-to-event illustrations, if present, use total event counts rather than participants per arm. The reported planning examples discussed for the continuous and binary outcomes are per arm. All such figures depend on the assumed effect, allocation, test threshold, and approximation; changing those assumptions would change the planning requirement.

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 = 48.300; pooled standard deviation σ = 90.972.
2. n = 2 × (1.96 + 0.842)² × 90.972² / 48.300² = 55.7, rounded up to 56 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 <- 48.3                      # observed difference in means
sigma <- 90.9721418831193                     # 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(5558410)
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 = 56 (80% power), 75 (90% power)
 75% of observed effect: n per arm = 100 (80% power), 133 (90% power)
 50% of observed effect: n per arm = 223 (80% power), 299 (90% power)
power.t.test: 56.7 
Simulated power at n = 56 per arm: 0.795 (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's primary analysis is reported as ANCOVA for superiority, with p < 0.001 for the comparison of suzetrigine with placebo. The registry supplies no ANCOVA estimate or confidence interval in the reported analysis record, but it does post least-squares means, standard errors, and a mean difference with a confidence interval. The simple recalculation from those summary statistics gives an unadjusted comparison, not the sponsor's adjusted model result.

The recalculated primary contrast is 48.3, with an interval from 33.67 to 62.93 and an unadjusted p-value below 0.001. Its direction and broad inferential conclusion are consistent with the sponsor's reported analysis. The registry does not flag a discrepancy. This agreement does not make the recalculation identical to ANCOVA: the reconstruction uses summary statistics and approximated standard deviations, while the sponsor's analysis is the reported model-based result.

The sponsor's analysis takes precedence as the trial's own inferential analysis. Recalculated values are useful as a check on how posted group summaries relate to the contrast, but they should not be presented as the sponsor's adjusted estimate. For the secondary active-treatment SPID48 comparison, the sponsor's reported ANCOVA p-value is 0.278, while the unadjusted recalculation gives p = 0.278. The close rounded values are consistent, but the two analyses still have different roles and assumptions.

15. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is identified, and the sponsor's analysis is described as ANCOVA for superiority. The registry record does not report whether the primary test was adjusted for any multiplicity issue, how secondary endpoints were ordered or prioritized, or whether a family-wise error procedure or other multiplicity control was used. It also does not report a detailed statistical analysis plan. With numerous outcomes and comparisons, the lack of a reported procedure limits how strongly secondary p-values can be interpreted as confirmatory.

The trial record defines the full analysis set for the primary outcome as randomized participants who received at least 1 dose of study drug. This is useful information about the primary analysis population. The registry does not report whether every secondary endpoint used that same population, nor does it provide a complete accounting of participants included in each analysis beyond endpoint-specific group counts. The safety denominators differ from the primary outcome denominators, underscoring that analysis populations can vary by outcome.

Missing-data methods are not reported in the registry record. The registry entries do not describe how missing pain ratings were handled, whether any imputation was used, or how participants who stopped study drug or discontinued assessments were treated in the primary analysis. Without those details, it is not possible to assess the sensitivity of the result to missing outcome measurements or to distinguish a complete-case analysis from other approaches.

The registry record also does not report interim analyses, stopping rules, or the trial's original sample-size justification. These should not be inferred from the final enrollment or from retrospective planning illustrations based on the observed effect. The absence of these details is a reporting limitation; it does not establish that a procedure was or was not used. Interpretation should therefore rely on the endpoint definition, population, estimates, and named tests that are explicitly reported, while treating undisclosed analysis choices as unknown.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: post procedural haematoma (0.9%), disseminated intravascular coagulation (0.5%), cardiogenic shock (0.5%), drug hypersensitivity (0.5%), post procedural haemorrhage (0.5%).

The posted safety summary reports serious adverse events affecting 5 of 222 participants in the placebo group, 7 of 448 in the HB/APAP group, and 11 of 448 in the suzetrigine group. Deaths were reported for 1 participant in the placebo group and none in the HB/APAP or suzetrigine groups. These are observed counts with the listed at-risk denominators; they are descriptive figures, not adjusted comparisons.

The registry also lists serious-event terms with percentages, including post procedural haematoma at 0.9%, and disseminated intravascular coagulation, cardiogenic shock, drug hypersensitivity, post procedural haemorrhage, and pulmonary embolism, each at 0.5%. The record details do not assign each listed percentage to a treatment group. The listed terms should not be interpreted as a complete catalogue of all adverse events.

Counts alone do not show whether an event was caused by a study drug, and small differences in counts do not establish comparative risk. The registry entries do not report a formal statistical test of serious adverse events or detailed event attribution. The safety figures should be read as the registry's descriptive summary, alongside the treatment groups and denominators, rather than as a definitive comparative safety conclusion.

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

The primary result describes a difference in average SPID48 scores between the suzetrigine and placebo groups in the trial's full analysis set. The posted estimate is positive in the direction of a higher score for suzetrigine under the registry's score definition, and the sponsor's reported ANCOVA test is a superiority result. The confidence interval communicates uncertainty about the size of that average contrast.

The result does not show that every participant had a better outcome, nor does it state how any individual participant would respond. It does not establish the importance of the difference to participants, because a threshold for clinical importance is not reported in the registry record. It also does not describe pain outcomes beyond the 0-to-48-hour primary window.

The trial studied acute pain after abdominoplasty and compared specific treatment regimens, including a placebo comparison and an active-treatment comparison. The findings should not automatically be generalized to other procedures, pain conditions, dosing schedules, or populations. The registry record does not provide enough detail to assess every aspect of external applicability, including participant characteristics beyond the stated condition and analysis population.

Secondary outcomes can add perspective, but they address different questions and some have distinct comparators or observation windows. The active-treatment SPID48 comparison does not establish equivalence, and unadjusted secondary tests have limited confirmatory force when multiplicity procedures are not reported. Safety counts likewise describe observed events without proving treatment causation or providing a formal comparative assessment.

Statistically, the central result is an estimated group contrast supported by a reported sponsor test and an interval that excludes zero. It is not a complete account of the balance of benefits and harms, nor a treatment recommendation. Decisions about care require clinical context and evidence beyond these registry results.

18. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition matters. SPID48 is not a single pain rating: it combines pain-intensity differences over time and weights them by the time between assessments. That summary targets accumulated experience across a defined 48-hour window. Readers therefore need to interpret its units, direction, and time frame before considering the numerical contrast.

It also demonstrates the distinction between a sponsor's model-based analysis and a simple reconstruction from posted summary statistics. The sponsor identifies ANCOVA, while the recalculation is unadjusted and depends on approximations from the available summaries. Agreement in direction can provide a useful consistency check, but does not erase the difference between methods or make the reconstruction the primary analysis.

The study includes placebo and active-treatment comparisons, along with secondary outcomes of different types. These provide multiple lenses on pain, patient assessment, and adverse events, but they also create interpretive complexity. A nonsignificant active-comparator test is not proof of equivalence, and significant unadjusted results across several secondary outcomes require caution when multiplicity handling is not reported.

Finally, the record shows why precision and reporting completeness should be considered together. A confidence interval gives more information than a p-value alone, while missing details about model covariates, missing data, and multiplicity restrict independent appraisal. The statistical result is meaningful as a defined comparison in a specific trial, but its scope depends on the outcome, analysis population, observation period, and reporting available.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several trial-specific details needed for a fuller statistical assessment are not reported in the registry record. The ANCOVA model's covariates and specification are not given, so readers cannot determine what adjustment was performed or independently reproduce the sponsor's analysis. The record also does not describe missing-data handling for pain ratings or provide sensitivity analyses to show whether conclusions depend on those choices.

The primary outcome groups have different reported sizes, and safety denominators differ from the primary endpoint denominators. The registry defines the primary full analysis set but does not give a complete participant flow or explain all endpoint-specific exclusions in the registry record reported. The reasons for the different counts are therefore not reported.

Multiplicity handling is not reported despite the range of secondary outcomes and comparisons. Consequently, the evidential status of individual secondary p-values is uncertain, and results should not be treated as independently confirmatory without additional analysis-plan information. Numerical findings are not available in the registry record details for every listed secondary outcome.

The active-treatment SPID48 comparison has a confidence interval that includes zero, but no equivalence or non-inferiority margin is reported. It cannot answer whether the treatments are sufficiently similar under a prespecified clinical criterion. The posted safety summary is descriptive; details of event attribution and a formal comparative safety analysis are not reported.

Finally, the registry entries do not describe participant characteristics in enough detail to assess how well the analyzed population represents other clinical settings. The endpoint captures a specific period after dosing, and evidence beyond that period is not established by the primary measure. These limitations concern the information available in the registry record and should not be mistaken for proof that unreported analyses or procedures were not conducted.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Evaluation of Efficacy and Safety of Suzetrigine for Acute Pain After an Abdominoplasty — NCT05558410.
• Registry record last updated 2025-07-01; status last verified 2025-06.
• Results first posted 2025-07-01.
• 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, quadruple-masked, parallel-group phase 3 study of suzetrigine for acute pain after abdominoplasty. It reports enrollment of 1118 participants and a primary SPID48 comparison of suzetrigine with placebo in the full analysis set.

The primary least-squares means were 118.4 for suzetrigine and 70.1 for placebo. The reported mean difference was 48.3, with a 95% confidence interval from 33.67 to 62.93. The sponsor reported an ANCOVA superiority analysis with p < 0.001. The simple recalculation is unadjusted and should be distinguished from that sponsor analysis.

Secondary outcomes include an active-treatment pain-score comparison, patient global assessment, and nausea or vomiting, among other listed measures. Safety summaries report serious adverse event counts and deaths by group. Multiplicity procedures, detailed missing-data methods, ANCOVA covariates, and the original sample-size justification are not reported in the registry record.