A Trial to Evaluate CG5503 Efficacy and Safety in Acute Pain After Bunionectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial to Evaluate CG5503 Efficacy and Safety in Acute Pain After Bunionectomy (NCT00609466), a randomized phase 3 study. The primary outcome is Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity..

2. Clinical Question

3. Trial Design

The registry describes a phase 3, randomized, quadruple-masked, parallel-group trial of CG5503 IR for acute postoperative pain following bunionectomy. It lists 291 participants enrolled and identifies CG5503 IR, morphine, and placebo as the interventions. The study status is completed. The record describes the comparison as active- and placebo-controlled; the primary comparison discussed in the posted analysis is CG5503 versus placebo.

The CG5503 arm received 75 mg every 4 to 6 hours for 72 hours. The active comparator arm received morphine IR 30 mg at the same interval and duration, while the placebo arm received matching placebo at that interval and duration. The registry identifies the model as parallel group and allocation as randomized. It does not report the method used to generate the allocation sequence or the procedures used to conceal allocation.

The primary endpoint analysis population is defined as randomized participants who were dosed and had a baseline pain-intensity assessment. The endpoint record reports 96 participants in the CG5503 arm, 93 in the morphine arm, and 96 in the placebo arm. These endpoint analysis counts should not be conflated with the enrollment total: the registry does not describe every reason for any difference between enrollment and endpoint analysis populations.

The primary endpoint timeframe ran from baseline to 48 hours after first study-drug intake. The record also lists secondary outcomes covering rescue medication use, total pain relief, and pain-intensity differences over shorter or longer follow-up intervals. The trial's original sample-size justification, planned interim analyses, detailed protocol, and full statistical analysis plan are not reported in the registry record. The sample-size illustrations associated with the observed effects are retrospective planning exercises, not evidence of the trial's original design assumptions.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: The trial consisted of a Screening Period (Day -28 up to the first surgical incision on Day -1), a Surgical Period (Day -1 to Day 1 at approximately 03:00 h.), a Qualification Period (Day 1), a Double-Blind Treatment Period (Day 1 up to Day 4), and a Follow-up Period (Day 8 up to Day 18).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to Treat - randomized subjects who were dosed and had a baseline pain intensity assessment. Last observation carried forward was used.

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 Sum of Pain Intensity Differences Relative to the Baseline Pain Intensity., measured over Baseline value to 48 hours after first study drug intake..

The primary endpoint is the sum of pain-intensity differences from baseline, measured from baseline to 48 hours after the first study-drug intake. Pain intensity was assessed at predefined time points on an 11-point Numeric Rating Scale, with zero indicating no pain and ten indicating pain as bad as you can imagine. At each time point, the endpoint difference was defined as baseline pain intensity minus post-baseline pain intensity, and those differences were accumulated into SPID48.

Under this definition, a larger positive sum represents more accumulated reduction in pain intensity relative to baseline; a negative value can indicate an increase in pain. The theoretical range is -480 to 480. The endpoint therefore combines repeated pain-intensity assessments across the stated interval into a continuous summary rather than describing pain at only one time point.

This type of summary can be useful when the research question concerns the pattern of pain intensity over a period, rather than an isolated assessment. It also requires interpretation in light of the assessment schedule, the calculation of differences, and the handling of missing observations. The registry states that last observation carried forward was used in the primary analysis population. The record does not provide the detailed timing of each scheduled assessment or further information about how the endpoint behaves for participants with incomplete measurements.

7. Results Posted in the Registry

• CG5503: mean 46.20 versus -17.50 on control; difference 63.70 (95% CI 29.34 to 98.06), standardized effect d = 0.52; z-test p = <0.001.
• Morphine: mean 102.50 versus -17.50 on control; difference 120.00 (95% CI 81.72 to 158.28), standardized effect d = 0.90; 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 Using 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:
  • CG5503: 64.6% (62/96) versus 85.4% (82/96) on control; risk difference -20.8 percentage points (95% CI -32.7 to -8.9), risk ratio 0.76 (0.64–0.90); unadjusted two-proportion z-test p = <0.001.
  • Morphine: 49.5% (46/93) versus 85.4% (82/96) on control; risk difference -36.0 percentage points (95% CI -48.3 to -23.6), risk ratio 0.58 (0.46–0.72); 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 CG5503 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Morphine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Total Pain Relief (TOTPAR)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • CG5503: mean 79.20 versus 41.80 on control; difference 37.40 (95% CI 23.18 to 51.62), standardized effect d = 0.74; z-test p = <0.001.
  • Morphine: mean 81.60 versus 41.80 on control; difference 39.80 (95% CI 24.49 to 55.11), standardized effect d = 0.74; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for CG5503 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Morphine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Sum of Pain Intensity Differences Over 6 Hours (SPID6) Relative to the Baseline Pain Intensity

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • CG5503: mean 8.00 versus -1.20 on control; difference 9.20 (95% CI 5.44 to 12.96), standardized effect d = 0.69; z-test p = <0.001.
  • Morphine: mean 8.00 versus -1.20 on control; difference 9.20 (95% CI 5.09 to 13.31), standardized effect d = 0.64; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for CG5503 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Morphine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes cover rescue medication use, total pain relief, and pain-intensity differences at several follow-up durations. In broad terms, the comparisons with placebo tend to align directionally with the primary endpoint: the reported estimates favor higher pain-relief or pain-intensity-difference summaries in the active arms, and fewer participants using rescue medication. The secondary results therefore provide related, supportive descriptions of outcomes measured during the trial, rather than independent confirmation of every aspect of the primary result.

These outcomes are related because they concern pain experience and management over overlapping periods. They are not interchangeable: a pain-intensity summary, a pain-relief summary, and rescue-medication use capture different aspects of the trial experience. Agreement in broad direction can add context, while differences in measurement and analysis mean that one outcome cannot stand in for another.

The registry reports some adjusted analyses for secondary outcomes and unadjusted comparisons for others. The full analysis plan and a multiplicity strategy are not reported in the registry record. When several outcomes and comparisons are examined, unadjusted p-values do not control the overall chance of a false-positive finding across that collection of tests. Accordingly, secondary p-values should carry less weight than the designated primary analysis, particularly when no adjustment or prespecified hierarchy is reported.

The secondary outcomes should be interpreted as a pattern of posted findings, not as a collection of separate definitive claims. Their consistency with the primary endpoint may be informative, but it does not resolve the missing details about outcome selection, analysis planning, or missing-data handling. The registry's reported results do not establish whether all planned secondary analyses were posted.

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

• Number of Participants Using Rescue Medication
• Total Pain Relief (TOTPAR)
• Sum of Pain Intensity Differences Over 6 Hours (SPID6) Relative to the Baseline Pain Intensity
• Sum of Pain Intensity Differences Over 12 Hours (SPID12) Relative to the Baseline Pain Intensity
• Sum of Pain Intensity Differences Over 24 Hours (SPID24) Relative to the Baseline Pain Intensity
• Sum of Pain Intensity Differences Over 72 Hours (SPID72) Relative to the Baseline Pain Intensity

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference describe?

A mean difference compares the average outcome in one arm with the average outcome in another. For the primary CG5503-versus-placebo comparison, the recalculated mean difference is formed from the posted arm means. Because the endpoint is constructed so that higher values indicate greater accumulated reduction in pain intensity, a positive difference points toward a higher average endpoint value in the CG5503 arm than in placebo. This is a description of the measured endpoint, not a general conclusion about all aspects of treatment or pain.

The recalculation uses only arm-level summary statistics and does not adjust for participant-level characteristics. It is useful as a transparent check on the magnitude and direction of the posted means, but it does not reproduce an adjusted model. The registry's ANCOVA result is a least-square mean comparison and is reported separately.

What does ANCOVA contribute?

Analysis of covariance, or ANCOVA, compares groups while accounting for specified covariates in a statistical model. In a randomized trial, adjustment can improve precision when relevant baseline measures are included and can account for chance differences in those measures. The registry reports an ANCOVA least-square mean difference for the primary comparison, but the covariates, model details, and diagnostics are not reported in the registry record. The reported adjusted result should therefore be read as the registry's estimate from that model, without assuming details that are not stated.

Adjusted and unadjusted estimates may differ because they answer the comparison using different statistical procedures. A difference between estimates is not, by itself, evidence that one is erroneous. The posted recalculation is not a substitute for the sponsor's analysis, and the registry's report remains the source for the ANCOVA result.

How should the p-values be read?

A p-value describes how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of a result. The unadjusted recalculation reports p < 0.001 for CG5503 versus placebo, while the registry-reported ANCOVA comparison reports p < 0.001. These values are from different analyses and should not be treated as interchangeable measures of effect size.

A small p-value does not eliminate uncertainty about the estimate, the endpoint definition, missing observations, or the applicability of the trial population. Confidence intervals are more directly informative about the range of effect estimates compatible with the analysis, subject to its assumptions.

Why does variability matter?

Standard deviations describe how spread out participant-level outcomes are around each arm mean. Larger spread relative to the difference between means generally makes an estimate less precise, all else being equal. The recalculated continuous-outcome comparisons use pooled standard deviations derived from the posted arm summaries. Pooling provides a common variability estimate for the unadjusted comparison under the calculation's assumptions. It does not establish that all participants had similar responses or that the endpoint follows a particular distribution.

For the primary CG5503-versus-placebo comparison, the posted standard deviations are 130.8 and 111.3. These values describe dispersion in the endpoint, not uncertainty in the arm means themselves. The standard errors and confidence interval reflect the precision of the estimated comparison, which depends on both variability and the number of analyzed participants.

What does randomization and masking mean?

Random allocation is intended to make treatment assignment independent of participants' measured and unmeasured characteristics on average, supporting a fair comparison. It does not guarantee identical groups in a particular trial. Masking is intended to reduce the influence of treatment knowledge on participant reports, clinical management, or assessment. The registry labels the trial quadruple-masked, but does not explain which roles were masked or the operational procedures used. These design labels should be understood as reported descriptions, not as a substitute for protocol details.

The parallel-group structure means participants were assigned to an arm and outcomes were compared across arms. The record does not report a crossover design. The primary analysis population is not described as every randomized participant: it includes those who were dosed and had a baseline pain-intensity assessment. That distinction matters when considering the interpretation of randomization and potential exclusions from analysis.

How does last observation carried forward affect interpretation?

Last observation carried forward is a method for filling a missing follow-up value with a participant's most recent observed value. It creates a complete dataset for the endpoint calculation but relies on an assumption that the carried-forward observation is a reasonable stand-in for the unobserved value. That assumption may be inappropriate if the underlying outcome would have changed after the last measurement. The registry identifies this method but does not report the amount or pattern of missing data, reasons for missingness, or sensitivity analyses using alternative assumptions.

The methods reported support a description of the posted results, but the absence of detailed model and missing-data information limits independent assessment of robustness. The original statistical plan, including any multiplicity strategy or interim analyses, is not reported in the registry record.

11. Confidence Intervals and Precision

A confidence interval expresses statistical uncertainty around an estimated comparison. The interval is constructed by a method that, under its assumptions, would cover the target quantity at the stated rate over repeated applications. It is not a range that guarantees where the true effect lies, and it does not account automatically for every source of uncertainty, such as incomplete reporting or analysis choices.

For the unadjusted recalculation of the primary CG5503-versus-placebo comparison, the estimated mean difference is 63.7 and the 95% confidence interval runs from 29.34 to 98.06. The interval is entirely above zero, so the estimated direction is positive throughout the interval. The registry-reported ANCOVA estimate is 70.8, with a 95% confidence interval from 35.9 to 105.6. Its limits likewise remain above zero. These intervals describe uncertainty for their respective analyses, not one shared estimate.

The recalculated and registry-reported intervals differ because the estimates come from unadjusted and adjusted analyses. The registry does not report the details needed to assess how the ANCOVA covariates affected precision. The interval width also reflects the observed variability and the analysis sample; the posted standard deviations indicate substantial spread in the endpoint within the arms.

Confidence intervals do not describe the range of individual participant outcomes. Nor do they settle whether a difference is clinically important: the registry record does not report a threshold for a clinically meaningful change in SPID48. Precision should therefore be considered alongside the endpoint's construction, the analysis population, and the limitations of last observation carried forward. The intervals quantify sampling uncertainty under the specified analyses, but do not resolve missing-data assumptions, multiplicity, or generalizability.

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 effects, not the trial's original design assumptions. For the continuous endpoint comparisons, the figures are participants per arm. For a time-to-event calculation, the convention would be total events, but the posted comparisons are continuous or binary outcomes and their planning figures are participants per arm.

The calculations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They illustrate planning for the stated fraction of the observed effect. The original trial's sample-size justification and assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm indicated by the calculation to provide an 80% chance of rejecting the null hypothesis if the assumed effect is the true effect, subject to the calculation's assumptions. The 90% power column gives the corresponding planning number for a 90% chance. These are conditional design illustrations, not guarantees of a trial result.

The rows for planning at 100%, 75%, and 50% of the observed effect show how the required sample size changes when the target effect is smaller than the observed estimate. Smaller effects need more participants to detect with the same planned power and significance level, all else being equal. Because the observed effect may be an uncertain estimate, these illustrations should not be treated as a recommendation or as evidence about the trial's actual design. This is not observed power; observed power is not a useful substitute for interpreting the estimated effect and its confidence interval.

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 = 63.700; pooled standard deviation σ = 121.444.
2. n = 2 × (1.96 + 0.842)² × 121.444² / 63.700² = 57.1, rounded up to 58 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 <- 63.7                      # observed difference in means
sigma <- 121.444435442716                     # 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(609466)
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 = 58 (80% power), 77 (90% power)
 75% of observed effect: n per arm = 102 (80% power), 136 (90% power)
 50% of observed effect: n per arm = 229 (80% power), 306 (90% power)
power.t.test: 58 
Simulated power at n = 58 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor's primary comparison as an ANCOVA least-square mean difference of 70.8, with a 95% confidence interval from 35.9 to 105.6 and p < 0.001. That is the trial's reported adjusted analysis for CG5503 versus placebo. The registry does not report the covariates or further details of the ANCOVA model.

The recalculated unadjusted comparison from the posted means and standard deviations is 63.7, with a 95% confidence interval from 29.34 to 98.06 and p < 0.001. This calculation does not adjust for covariates and therefore answers the comparison using a different method. The estimates are not identical, but both are positive and their intervals exclude zero.

The recalculation is a transparent secondary check on the arm summaries, not a correction to the sponsor's analysis. The registry does not flag a discrepancy between the posted result and recalculation. For interpretation of the sponsor's prespecified analysis, the sponsor-reported ANCOVA result takes precedence over an unadjusted reconstruction. The registry does not provide enough information to reproduce that adjusted estimate independently.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists secondary outcomes, but it does not report a multiplicity-control procedure or a hierarchy for formal testing. Multiplicity arises when multiple hypotheses are tested: even if each test uses a conventional threshold, the chance of at least one false-positive result across a collection of tests can increase. Without a stated adjustment or testing sequence, secondary p-values should be read as unadjusted evidence for their individual comparisons, not as confirmatory results protected against the full set of analyses.

The record also does not report whether interim analyses were planned or conducted. Any interim monitoring or changes to the statistical plan are therefore not assessable from the registry entry. The original statistical analysis plan, including prespecified covariates and decisions about secondary endpoints, is not reported in the registry record.

For the primary endpoint, the analysis population consisted of randomized participants who were dosed and had a baseline pain-intensity assessment. Last observation carried forward was used. The record does not report the extent, timing, or reasons for missing outcome data, nor does it describe sensitivity analyses comparing the carried-forward method with alternative approaches. Last observation carried forward may not represent an unobserved outcome accurately if pain changes after the last measurement.

The record does not provide a complete participant flow or explain all differences between enrolled participants and the endpoint analysis counts. It also does not state whether analyses followed an intention-to-treat principle beyond the posted population description. These gaps make it difficult to assess possible effects of exclusions or missingness. The posted estimates remain interpretable as analyses of the defined population using the stated method, while robustness to other assumptions cannot be established from the registry record.

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

The results describe a randomized comparison of pain-related outcomes after bunionectomy in the trial population. For the primary endpoint, both the unadjusted recalculation and the registry-reported ANCOVA comparison estimate a higher mean SPID48 in the CG5503 arm than in the placebo arm, and both reported confidence intervals exclude zero. This is evidence about the specified endpoint, time interval, population, and analyses.

The result does not establish that every participant experienced a similar outcome. The standard deviations show that individual endpoint values varied within each arm, while a group mean difference describes only an average comparison. The confidence intervals quantify uncertainty around group-level estimates; they do not predict an individual participant's response.

The result does not establish a clinically meaningful threshold because such a threshold is not reported in the registry record. Statistical evidence against a zero difference is not the same as evidence that a difference has a particular importance to participants. Nor does the primary endpoint capture every dimension of postoperative pain, function, safety, or recovery.

The trial included morphine as an active comparator, but the registry's primary reported adjusted analysis is CG5503 versus placebo. The posted unadjusted morphine comparison is not evidence of equivalence or non-inferiority between the active arms. Such a conclusion would require an appropriate objective, margin, and analysis, none of which is reported in the registry record.

Safety interpretation is also limited. The registry lists serious adverse events affecting zero participants in the CG5503 arm, one in the morphine arm, and zero in the placebo arm, but the numbers at risk are not reported. Other adverse events are listed as affecting 69, 85, and 47 participants, respectively, again without arm-specific numbers at risk in this record. These counts cannot be interpreted as comparative rates without the missing denominators and fuller event context. Death counts are not reported. The findings therefore do not settle broader questions about safety, outcomes outside the recorded follow-up, or effects in populations not represented by this trial.

17. Why This Trial Matters Statistically

This trial illustrates why a registry result should be read through both its endpoint definition and its analysis method. SPID48 is an accumulated summary of repeated pain-intensity differences, not a single pain rating. Understanding the direction of the difference depends on the stated calculation: baseline minus post-baseline pain intensity, summed over assessments. Without that definition, the sign and clinical interpretation of a mean difference could be misunderstood.

The record also places an adjusted sponsor analysis beside an unadjusted reconstruction from arm summaries. The estimates are close in direction but not identical. Distinguishing those procedures prevents a summary-statistic recalculation from being mistaken for a reproduction of ANCOVA. It also highlights why covariate details matter when readers want to understand or reproduce an adjusted result.

Another statistical lesson is that significance and precision are related but distinct. The p-values indicate incompatibility with a null model under their respective analyses, while confidence intervals communicate a range of estimates compatible with the data and assumptions. Neither measure determines clinical importance, and neither removes uncertainty caused by missing observations or incomplete reporting.

Finally, the trial contains multiple secondary outcomes, but the registry does not report a multiplicity strategy. A coherent pattern across related measures can be useful context, yet unadjusted secondary tests should not be treated as if each were an independently planned confirmatory claim. The record makes visible both the evidence and the limits of what can be inferred from registry reporting.

18. Limitations

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

The registry record leaves important details unavailable for assessing the trial's methods. It does not report the original sample-size justification, the allocation-generation and concealment procedures, the roles covered by quadruple masking, or the full statistical analysis plan. The ANCOVA covariates and model diagnostics are not reported, limiting independent reproduction of the adjusted estimate.

The primary population was restricted to randomized participants who were dosed and had a baseline assessment. The registry does not provide a full account of participant flow or explain the difference between enrollment and the arm counts used for the endpoint. The extent and reasons for missing outcome data are also not reported. Last observation carried forward was used, but no sensitivity analyses are described to show how results might change under alternative missing-data assumptions.

The record does not state how multiplicity across primary and secondary outcomes was addressed, whether any interim analyses occurred, or whether every planned outcome analysis was posted. Consequently, the secondary p-values cannot be interpreted as multiplicity-adjusted evidence unless such adjustment is documented elsewhere; it is not reported in the registry record.

Safety entries lack the arm-specific numbers at risk, and death counts are not reported. The available event counts therefore do not support rate comparisons from this record alone. The registry also does not report a threshold for clinical importance on the primary endpoint. These limitations do not erase the posted statistical results, but they restrict assessment of their robustness, clinical relevance, and completeness.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Trial to Evaluate CG5503 Efficacy and Safety in Acute Pain After Bunionectomy — NCT00609466.
• Registry record last updated 2011-11-16; status last verified 2011-11.
• Results first posted 2009-11-25.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

The registry describes a completed, randomized, quadruple-masked, parallel-group phase 3 trial of CG5503 IR after bunionectomy, with 291 participants enrolled. The arms received CG5503 IR 75 mg, morphine IR 30 mg, or matching placebo every 4 to 6 hours for 72 hours.

The primary endpoint was SPID48, the sum of baseline-minus-post-baseline pain-intensity differences from baseline to 48 hours. The registry-reported ANCOVA comparison of CG5503 with placebo was 70.8, with a 95% confidence interval from 35.9 to 105.6 and p < 0.001. The unadjusted recalculation was 63.7, with a 95% confidence interval from 29.34 to 98.06 and p < 0.001. The record identifies last observation carried forward but does not report the full statistical plan, multiplicity handling, original sample-size justification, or sensitivity analyses for missing data.