A Safety and Effectiveness Study of SABER®-Bupivacaine for Pain Following Shoulder Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety and Effectiveness Study of SABER®-Bupivacaine for Pain Following Shoulder Surgery (NCT00818363), a randomized phase 2 study. The primary outcome is Mean Pain Intensity on Movement AUC (Time Normalized Area Under the Curve) During the Period 0 to 72 Hours Post-dose..

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, parallel-group, placebo-controlled trial of SABER-Bupivacaine after arthroscopic shoulder surgery. The registry record identifies the study as quadruple-masked and reports an enrollment of 60 participants. The treatment groups received one 5.0 mL dose of SABER-Bupivacaine or one 5.0 mL dose of SABER-Placebo. The posted group counts for the primary outcome are 40 and 20, respectively.

The official title describes the study as double-blind and multicenter, while the registry’s masking classification is quadruple. The identities of the groups of people included in that masking classification, and details of the allocation process, are not reported in the registry record. The sponsor was Durect. The recorded study start was 2008-12, the primary completion was 2009-10, and the study status is completed.

The primary outcome was mean movement-related pain intensity AUC, normalized over the interval from 0 to 72 hours after dosing. The record also lists secondary outcomes concerning pain over 0 to 48 hours, supplemental opioid use, opioid-related adverse events, time to first supplemental opioid use, and severity of opioid-related side effects. The registry record does not report the original sample-size justification, the trial’s planned allocation ratio, details of the treatment administration setting, or the full eligibility criteria. Those details should not be inferred from the observed group sizes or outcome summaries.

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

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 Mean Pain Intensity on Movement AUC (Time Normalized Area Under the Curve) During the Period 0 to 72 Hours Post-dose., measured over 0 to 72 hours post-dose.

The primary endpoint summarizes movement-related pain intensity over the 0 to 72 hours after dosing. Participants assessed pain using an 11-point Pain Intensity Numeric Rating Scale, ranging from 0 for no pain to 10 for the worst pain possible. For each participant, the recorded pain scores were used to calculate an area under the curve with the trapezoidal rule. The area was then divided by the length of the time interval to produce a time-normalized AUC.

As a general statistical explanation, an area-under-the-curve summary combines repeated measurements over a specified period rather than representing a single assessment. Normalizing by the interval length makes the reported measure easier to interpret on the scale of pain intensity, because it expresses an average over the interval rather than an accumulated area that grows with time. It can therefore capture the overall pattern of measured pain during the defined period, while not showing when within that period pain was higher or lower.

The endpoint is continuous, and the registry reports group means and standard deviations. Lower scores correspond to lower reported pain intensity on the described scale. The measure concerns movement-related pain; it should not be interpreted as a measure of pain at rest, later recovery, or every aspect of postsurgical experience.

7. Results Posted in the Registry

• Group 1: SABER-Bupivacaine: mean 5.35 versus 5.81 on control; difference -0.46 (95% CI -1.61 to 0.69), standardized effect d = -0.23; z-test p = 0.433.

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.

Mean Pain Intensity on Movement AUC (Time-normalized AUC) During the Period 0 to 48 Hours Post-dose (0 to 2 Days Post-dose).

• 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:
  • Group 1: SABER-Bupivacaine: mean 5.65 versus 6.14 on control; difference -0.49 (95% CI -1.66 to 0.68), standardized effect d = -0.23; z-test p = 0.411.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 1: SABER-Bupivacaine and the control. The interval gives the range of effects that remain compatible with the data.

Supplemental Opioid Use

• 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:
  • Group 1: SABER-Bupivacaine: mean 37.13 versus 43.70 on control; difference -6.57 (95% CI -24.51 to 11.37), standardized effect d = -0.23; z-test p = 0.473.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 1: SABER-Bupivacaine and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes spanning movement-related pain over a shorter interval, supplemental opioid use, opioid-related adverse events, time to first supplemental opioid use, and severity of opioid-related side effects. Numerical summaries are posted for pain AUC over 0 to 48 hours and supplemental opioid use over 0 to 48 hours. For both of these continuous summaries, the observed group means are lower in the SABER-Bupivacaine group than in the placebo group. Their unadjusted comparison intervals include no difference.

This directional pattern is consistent with the negative primary point estimate, but it does not turn the primary finding into a conclusive result. The outcomes measure different aspects of the postsurgical period, and a similar direction across a small set of measures does not establish a consistent effect across all endpoints. The registry record does not provide sponsor-reported inferential analyses for those two secondary continuous outcomes.

General statistical explanation: secondary endpoints are often numerous and may be examined in addition to a primary endpoint. When many outcomes are tested, the chance of at least one apparently notable result arising by chance can increase. Adjustments for multiplicity or a prespecified hierarchy can address some of this issue, but the registry record does not report whether such procedures were planned or used. For that reason, unadjusted secondary results generally carry less confirmatory weight than a prespecified primary analysis. They can describe patterns and motivate further study, but should not be treated as independent proof of an effect.

The record names opioid-related adverse event frequency, time to first supplemental medication use, and severity of opioid-related side effects among the secondary outcomes. Detailed numerical estimates for these measures are not included in the registry record for interpretation, so no direction or magnitude should be inferred for them.

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

• Number (Frequency) of Participants Reporting Opioid-related Adverse Events
• Mean Pain Intensity on Movement AUC (Time-normalized AUC) During the Period 0 to 48 Hours Post-dose (0 to 2 Days Post-dose).
• Supplemental Opioid Use
• Time-to-first Use of Opioid Supplemental Pain Medication
• Severity of Opioid-related Side Effects

9. Statistical Interpretation

10. Statistical Methods Explained

What does the primary measure summarize?

The primary measure is a mean of a continuous outcome: a time-normalized AUC of movement-related pain intensity during the 0 to 72 hours after dosing. The pain scores came from an 11-point PI-NRS, with 0 indicating no pain and 10 indicating the worst pain possible. The record says the AUC was calculated for each participant using the standard trapezoidal rule and then normalized by the time-interval length. The posted group summaries report a mean and standard deviation for each group.

As a general explanation, the trapezoidal rule approximates the area under a curve by joining observations across time and adding the resulting areas. In a repeated-measures setting, the AUC can summarize the overall experience across the selected interval. Normalization makes the summary an average intensity over that interval. It does not preserve the full sequence of individual pain assessments, so different time patterns can lead to similar summaries.

How should the mean difference be read?

The unadjusted recalculation expresses the difference as the SABER-Bupivacaine group mean minus the SABER-Placebo group mean. Thus, a negative value indicates a lower observed mean in the SABER-Bupivacaine group. The estimate of -0.46 is based on the posted group means of 5.35 and 5.81. It is a descriptive contrast of those summaries, not an adjustment for other variables.

As a general explanation, a mean difference retains the units of the measured scale, which makes it more directly interpretable than a standardized effect. A standard deviation describes the spread of individual values around a group mean. The registry reports standard deviations of 1.91 and 2.25 for the primary outcome. These describe variability among participants, not the uncertainty of the group difference itself.

What is the distinction between the two analyses?

The recalculated comparison is a simple, unadjusted calculation from posted summary statistics. It is not the trial’s full individual-participant analysis. The sponsor-reported analysis is ANCOVA and reports a least-squares mean difference. As a general explanation, ANCOVA compares groups while accounting for covariates included in the model; the resulting least-squares means are model-based estimates. The registry record does not identify the covariates, their coding, model diagnostics, or the analysis population, so the reported ANCOVA cannot be independently reconstructed from the record.

The sponsor reports a least-squares mean difference of -0.64, a 95% confidence interval from -1.74 to 0.47, and p = 0.303. The unadjusted recalculation estimates -0.46 and has p = 0.433. These are not identical because they are not the same analysis. The record does not flag a discrepancy between its results, and no claim about the reason for the difference should be made beyond the distinction between the reported ANCOVA and the unadjusted recalculation.

What do the p-value and confidence interval convey?

As a general explanation, a p-value evaluates how compatible the observed data are with a specified null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. Here, the sponsor-reported p-value is 0.303 and the unadjusted recalculated p-value is 0.433. Both are interpreted alongside the estimates and intervals, not in isolation.

As a general explanation, a confidence interval gives a range of values compatible with the data and analysis under the method’s assumptions. The sponsor’s 95% interval crosses zero, the value representing no mean difference. The recalculated interval also includes no difference. This means the analyses do not provide a statistically clear separation from zero at the conventional two-sided 0.05 level. It does not prove equality or rule out potentially meaningful effects.

Why does the analysis method matter?

General statistical explanation: an unadjusted comparison and a covariate-adjusted model can produce different estimates because they use information differently. A model may account for baseline or other measured characteristics if those variables are specified, but whether adjustment is appropriate and how it affects the result depends on the prespecified model and the data. The registry record does not report the original statistical analysis plan, the ANCOVA covariates, any interim analyses, or the sample-size justification. Consequently, the posted results support a description of the analyses reported, but not a full audit of the trial’s statistical conduct.

11. Confidence Intervals and Precision

The sponsor-reported primary estimate is a least-squares mean difference of -0.64, with a 95% confidence interval from -1.74 to 0.47. The interval crosses zero, so it includes both a negative difference and a positive difference as compatible values under the analysis. The reported p-value is 0.303. Together, these figures indicate uncertainty about the direction and magnitude of the group contrast rather than a precise estimate that excludes no difference.

The unadjusted recalculation gives a mean difference of -0.46 and an unadjusted p-value of 0.433. Its recalculated confidence interval also includes zero. The group standard deviations are 1.91 for SABER-Bupivacaine and 2.25 for SABER-Placebo, with 40 and 20 participants contributing to the posted group summaries. The unequal group counts and the overall enrollment of 60 are important context for the amount of information in the comparison.

As a general explanation, a confidence interval’s width reflects statistical precision: narrower intervals indicate less uncertainty about the estimated contrast, while wider intervals indicate more. An interval spanning zero does not demonstrate that the groups are identical; it indicates that the data do not distinguish the observed estimate from no difference at the stated confidence level. The interval also does not describe every possible source of uncertainty, including limitations arising from missing data, model choices, or outcome reporting.

The registry record does not provide a threshold for a clinically important difference on this normalized AUC measure. Statistical precision and clinical importance are therefore distinct questions, and the latter cannot be resolved from the reported estimates alone.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

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

The 80% power column describes the planned number of participants per arm under those assumptions for an analysis with an 80% chance of detecting the specified effect, if that effect and the assumptions were correct. The 90% power column uses the same idea with a higher target chance of detection, which generally requires more participants. These are design-planning quantities; they do not tell how likely the trial’s observed result was to be correct.

For the primary endpoint, the planning illustration gives 306 participants per arm for 80% power and 409 participants per arm for 90% power when planning for 100% of the observed effect. Planning for 75% of the observed effect gives 543 participants per arm for 80% power and 726 for 90% power. Planning for 50% of the observed effect gives 1,221 participants per arm for 80% power and 1,634 for 90% power. The pattern reflects the general principle that smaller effects are harder to distinguish from random variation and therefore require more participants.

These are not observed power calculations. They are hypothetical planning illustrations based on the observed effect and stated assumptions, not evidence that the completed study did or did not have a particular probability of success. They should not be read as a substitute for the trial’s original sample-size planning, which is not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.460; pooled standard deviation σ = 2.028.
2. n = 2 × (1.96 + 0.842)² × 2.028² / -0.460² = 305.0, rounded up to 306 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 <- -0.46                      # observed difference in means
sigma <- 2.02766810179439                     # 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(818363)
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 = 306 (80% power), 409 (90% power)
 75% of observed effect: n per arm = 543 (80% power), 726 (90% power)
 50% of observed effect: n per arm = 1,221 (80% power), 1,634 (90% power)
power.t.test: 306 
Simulated power at n = 306 per arm: 0.800 (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 an ANCOVA and gives a least-squares mean difference of -0.64, with a 95% confidence interval from -1.74 to 0.47 and p = 0.303. It is the registry’s reported model-based comparison. The covariates and analysis population used for ANCOVA are not reported in the registry record, so its details cannot be reconstructed from the posted group means and standard deviations.

The simple recalculation from the posted summaries is unadjusted. It gives a mean difference of -0.46 and p = 0.433. The estimates are directionally similar, but they are not numerically identical. This is not a like-for-like comparison: one is a least-squares mean difference from ANCOVA, while the other is a direct, unadjusted comparison of group means. The registry record does not flag a discrepancy, and the sponsor analysis should be understood according to its stated method rather than treated as interchangeable with the recalculation.

Both analyses have uncertainty that includes no difference. The recalculation is useful as a transparent check of the posted summaries, while the sponsor’s estimate is the reported ANCOVA result. Neither p-value should be read as a measure of treatment importance or as proof of no effect. The registry record does not provide enough detail to assess model assumptions, covariate selection, or any departures from the analysis plan.

15. Multiplicity, Missing Data and Analysis Populations

The record lists several outcomes in addition to the primary 0 to 72 hour pain AUC, including shorter-interval pain, opioid use, opioid-related adverse events, time to first supplemental opioid use, and severity of opioid-related side effects. Examining multiple endpoints can make isolated findings harder to interpret because repeated testing can increase the chance of a nominally notable result. General statistical methods for addressing multiplicity include adjusting the significance threshold or specifying a hierarchy of outcomes, but the registry record does not report whether either approach was planned or used.

The record also does not report whether interim analyses were conducted, whether the primary analysis population was intention-to-treat or another defined population, or how protocol deviations were handled. The original statistical analysis plan is not reported in the registry record. These omissions prevent a full assessment of prespecification and analysis choices; they are not evidence that a particular procedure was or was not used.

Missing-data handling is also not reported in the registry record. The posted primary group counts are 40 and 20, but the record does not explain whether these are all randomized participants, all participants treated, or only those with available primary endpoint data. It does not describe missing observations, reasons for missingness, imputation, or sensitivity analyses. As a general explanation, the impact of missing outcome data depends on how much is missing and on the relationship between missingness and the unobserved outcomes. Without these details, the potential effect of missing data on the comparison cannot be assessed.

The registry does not report baseline balance, participant flow by analysis population, or the exact covariates in the sponsor’s ANCOVA. This limits appraisal of whether the model was fully specified and how the analysis accounts for observed data. These reporting gaps call for caution in interpreting inferential details; they do not justify assuming a particular bias or analysis choice.

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: pyrexia (2.5%).

The posted serious adverse event figures are 1 participant affected among 40 at risk in the SABER-Bupivacaine group and 0 among 20 at risk in the SABER-Placebo group. The registry lists Pyrexia at 2.5% among the top serious adverse event terms. Deaths are reported as 0 in both groups. These are counts and a listed term, not a complete description of event timing, duration, severity, or relationship to treatment.

For other adverse events, the registry reports 38 participants affected among 40 at risk in the SABER-Bupivacaine group and 19 among 20 at risk in the placebo group. These figures refer to participants with other adverse events, not the number of individual events. The record does not provide a detailed breakdown of those events in the registry record for interpretation.

As a general explanation, adverse event counts describe what was reported during a study; they do not by themselves establish that a treatment caused an event. The group sizes differ, and this trial’s safety observations are limited to the enrolled participants and the recorded study period. The registry record does not provide enough detail to assess comparative risks for individual adverse events or uncommon harms.

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

The primary result is a comparison of mean movement-related pain AUC over 0 to 72 hours after dosing among participants in this trial. The observed SABER-Bupivacaine group mean was lower than the placebo group mean, and both the sponsor-reported ANCOVA and the unadjusted recalculation produced negative point estimates. Their confidence intervals include no difference, so the record does not show a statistically clear separation between groups on this outcome.

This does not mean the treatments have been shown to be equivalent. Demonstrating equivalence or noninferiority requires a suitable design, prespecified margins, and an analysis directed at that question; such details are not reported in the registry record. Nor does the result establish that there is no effect. The estimates are uncertain, and the trial enrolled 60 participants overall. A range of possible group differences remains compatible with the posted results.

The findings also do not establish a treatment effect on all dimensions of recovery. The primary endpoint measures movement-related pain averaged over a defined early postoperative interval. It does not directly summarize pain at rest, function, longer-term recovery, or every opioid-related outcome. The secondary outcomes address some additional questions, but their analysis and multiplicity procedures are not reported in enough detail to make them confirmatory.

Safety counts describe recorded events in the trial, not proof of causation or a complete accounting of risk. No deaths were reported, and the serious-event counts were small; those observations do not rule out events that would be difficult to detect in a trial of this size. The registry record should therefore be read as a report of a limited clinical comparison, not as a standalone basis for broad claims about benefit or safety.

General statistical explanation: an estimate, its uncertainty, the trial design, and the completeness of reporting all contribute to interpretation. A point estimate alone is not enough to establish importance, and a p-value alone cannot show that a result is clinically meaningful. The registry does not report a clinically important difference threshold for the primary endpoint, so statistical and clinical importance cannot be equated from these data.

18. Why This Trial Matters Statistically

This trial illustrates why an observed difference and a clear statistical conclusion are not the same thing. The primary point estimate favors a lower mean pain score in the SABER-Bupivacaine group, but the reported uncertainty spans no difference. Readers need both the direction of the estimate and the interval around it to understand what the data can distinguish.

It also illustrates the importance of identifying the analysis behind a result. The sponsor reports an ANCOVA least-squares mean difference, while the simple recalculation uses unadjusted group means. These analyses answer related but not identical statistical questions. Naming the method and its limits prevents the two estimates from being mistaken for the same calculation.

The study’s planning illustrations also show how sample-size requirements depend on the effect size a future study aims to detect. Smaller target effects require more participants under the listed assumptions. These calculations are not evidence about the power actually achieved in this completed trial, and the original design justification is not reported.

Finally, the record highlights how endpoint multiplicity, missing-data procedures, analysis populations, and model details affect confidence in interpretation. Several outcomes were considered, but the record does not describe multiplicity procedures or missing-data handling. Such information is important for judging whether an apparent pattern is robust and whether the reported analysis corresponds to the originally planned question.

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 original sample-size justification, so the adequacy of the planned enrollment for the primary question cannot be assessed from the record. The available sample-size illustrations are based on the observed effect and specified hypothetical assumptions, not on the trial’s documented original design calculation.

The posted primary outcome counts are unequal between groups, and the record does not explain the participant flow or whether all randomized participants contributed to the endpoint. Eligibility criteria, demographic characteristics, baseline outcome values, and detailed surgical or perioperative characteristics are not reported in the registry record. These omissions limit assessment of the enrolled population and the comparability of groups before treatment.

The sponsor’s ANCOVA is reported without its covariates, model diagnostics, analysis population, or handling of missing data. The registry record also does not report an analysis plan, multiplicity strategy, or interim analyses. These details matter for evaluating the model-based result and the interpretation of multiple endpoints, but their absence does not establish that a particular method was used or omitted.

The primary endpoint summarizes movement-related pain during an early postoperative interval and cannot describe the full time course of pain or outcomes outside that interval. The registry does not state a threshold for a clinically important difference on the normalized AUC measure. Safety results are presented as counts, with limited detail about event characteristics or attribution. The enrolled sample and posted serious-event counts cannot resolve questions about uncommon events.

Finally, the record identifies a completed Phase 2 trial but does not report enough detail to evaluate all aspects of conduct, adherence, or generalizability. These limitations narrow what can be concluded from the posted summaries; they should not be replaced by assumptions about unreported methods or findings.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Safety and Effectiveness Study of SABER®-Bupivacaine for Pain Following Shoulder Surgery — NCT00818363.
• Registry record last updated 2021-06-01; status last verified 2021-05.
• Results first posted 2021-06-01.
• 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

NCT00818363 is a completed, randomized, parallel-group, placebo-controlled Phase 2 trial sponsored by Durect. It enrolled 60 participants after arthroscopic shoulder surgery and compared a single 5.0 mL dose of SABER-Bupivacaine with a single 5.0 mL dose of SABER-Placebo. The official title describes a double-blind, multicenter trial; the registry classification lists quadruple masking.

The primary outcome was mean movement-related pain intensity AUC normalized over 0 to 72 hours after dosing. The sponsor-reported ANCOVA estimate was -0.64, with a 95% confidence interval from -1.74 to 0.47 and p = 0.303. A simple unadjusted recalculation gave a mean difference of -0.46 and p = 0.433. Both intervals include no difference. The registry also lists pain, opioid-use, and safety-related secondary outcomes.

The registry record does not report the original sample-size justification, missing-data procedures, analysis populations, or key ANCOVA details. Those gaps limit assessment of the analysis and the broader implications of the results.