Safety and Efficacy Study of XPF-001 to Treat Pain Following Wisdom Tooth Extraction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of XPF-001 to Treat Pain Following Wisdom Tooth Extraction (NCT00954356), a randomized phase 2 study. The primary outcome is Total Pain Relief at 6 Hours Post Dose (TOTPAR 6).

2. Clinical Question

The endpoint captures pain-relief ratings collected during the period after dosing, rather than a rating at one moment alone. Its score incorporates both the relief ratings and the time over which they were observed. Higher scores indicate more reported pain relief on this measure. The registry describes the trial as proof-of-concept and lists efficacy and safety among its aims. It does not report a formal between-arm effect estimate or a test of the primary comparison. The group estimates can therefore be described, but they should not be mistaken for a reported comparative analysis.

3. Trial Design

This was a Phase 2, single-center, randomized, double-blind, placebo-controlled, parallel-group study. The registry reports quadruple masking, without further detail in the record about which roles were masked. Its official title describes evaluation of the safety, pharmacokinetics and efficacy of a single oral dose of XPF-001 for pain related to third-molar or wisdom tooth extraction.

The registry reports enrollment of 61 participants. The outcome results list 41 participants for XPF-001 and 20 for placebo. Randomization was used, but the method for generating the allocation sequence and the allocation-concealment procedures are not reported in the registry record. The record also does not describe the drug dose, adherence, rescue medication, or other details that could help interpret treatment exposure.

The study began in 2009-09 and had primary completion in 2009-11; its status is completed. The record describes its primary efficacy measure as total pain relief at 6 hours after dosing. It also lists secondary measures of pain relief and pain intensity at other post-dose times, along with time to first perceptible relief. The registry does not report the details of the statistical model used for the primary outcome or how the primary comparison was tested. Its enrollment and the arm-specific estimates describe the posted record, but they do not establish how many participants contributed usable data to every analysis.

4. Participant Flow and Accounting

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

Overall Study

Analysis population for the primary outcome, as defined in the registry: Published data from an impacted wisdom tooth removal was used to determine a 60 subject study with 2:1 randomisation and a one-sided significance level of 0.10 would have a power of 84.1%. LOCF was used for imputed values and all subjects were included in both the IIT and PP populations for analysis.

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 Total Pain Relief at 6 Hours Post Dose (TOTPAR 6), measured over 6 hours post dose.

The primary endpoint, TOTPAR 6, summarizes pain relief during the 6 hours after dosing. Participants rated relief at multiple timepoints using a five-point categorical scale ranging from no relief to complete relief. TOTPAR 6 combines those ratings across time using an area calculation; the registry says it was calculated with Simpson’s trapezoidal rule. The possible score ranges from 0 to 24, and higher values represent more reported pain relief.

A measure accumulated over time can reflect both the degree of relief and how long that relief is observed. This differs from relying only on one rating at one timepoint, which could miss changes during the observation period. The registry identifies the endpoint as the primary efficacy variable and reports least-squares means with 95% confidence intervals. It does not give a between-arm difference with its own confidence interval or a comparative p-value.

The group results are XPF-001, 4.37 (95% confidence interval 2.79 to 5.96), and placebo, 2.45 (95% confidence interval 0.182 to 4.72). These estimates describe the reported endpoint for each arm. They should not be read as a direct estimate of the treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s TOTPAR 6 is a numerical score. The registry reports a least-squares mean for each treatment arm. A least-squares mean is a model-based estimate of a group mean; it may account for features of a statistical model. The record does not say what model was used, what terms it included, or whether the values were adjusted. It is therefore safest to retain the registry’s label rather than infer how the estimates were calculated.

What does the endpoint summarize?

Pain relief was rated at multiple timepoints on a five-point categorical scale. The registry describes the ratings as 0 for no relief, 1 for a little relief, 2 for some relief, 3 for a lot of relief, and 4 for complete relief. TOTPAR 6 combines relief ratings over the 6 hours after dosing into an area calculation using Simpson’s trapezoidal rule. In general, an area-under-the-curve measure reflects the pattern of measurements across time, not just a single observation. Here, the registry states that the higher the score, the more pain relief was obtained.

The endpoint’s scale has a stated minimum of 0 and maximum of 24. This helps define the range of possible results, but does not by itself describe the distribution of observed participant scores. The registry does not report individual-level scores, a standard deviation, or other information on the spread of scores within each arm.

How should the confidence intervals be read?

The 95% confidence intervals are reported around the arm-specific least-squares means. In general, a confidence interval expresses the statistical uncertainty associated with an estimate under the analysis assumptions. It is not a range guaranteed to contain the true value, and it does not indicate the probability that a particular treatment is better. The intervals concern separate group means. A confidence interval for the contrast between groups would directly describe uncertainty in the comparison; that result is not reported in the registry record.

The registry reports XPF-001 at 4.37, with an interval from 2.79 to 5.96, and placebo at 2.45, with an interval from 0.182 to 4.72. The intervals overlap. In general, overlap or non-overlap of separate group intervals is not a replacement for testing the difference between groups. The uncertainty in a contrast depends on the analysis and cannot be recovered merely by comparing the two intervals.

What is missing from the statistical description?

The record does not report the statistical model, the treatment contrast, the standard error for that contrast, a p-value, or a detailed analysis plan. It also does not state whether the primary comparison was adjusted for baseline measures or other covariates. Without these details, an independent reader cannot reproduce the comparative analysis or verify the assumptions used to obtain the reported least-squares means and intervals.

In general, assumptions matter because they determine how estimates and uncertainty are calculated. For a continuous measure, analysts consider the outcome’s distribution, the model’s fit, and whether the uncertainty calculation is appropriate. If observations are more variable than a model assumes, for example, uncertainty can be understated. This is a general statistical point, not a finding about this trial: the registry does not report diagnostics that would establish whether over-dispersion or other model concerns occurred.

What can planning calculations tell us?

The primary outcome description says published data from wisdom tooth removal were used to plan a 60-subject study with 2:1 randomization and a one-sided significance level of 0.10, and that the calculation yielded 84.1% power. This is a stated planning assumption and result, not an observed result. It does not show that the trial’s observed estimates have a particular probability of detecting an effect, nor does it establish that a treatment difference exists. The registry’s actual enrollment is 61, and the outcome results list 41 participants in the XPF-001 arm and 20 in placebo.

Separately, planning illustrations based on observed effects use two-sided significance level 0.05, equal allocation, and a normal approximation. Such illustrations are hypothetical designs for future studies, with the effect to detect defined as a fraction of the observed effect. They are not results from this trial and do not represent observed power. They should be interpreted as planning scenarios, not as evidence about the reliability of the trial’s treatment comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 secondary outcomes, including total pain relief at several post-dose times, summed pain intensity difference at several times, and time to first perceptible relief. The primary endpoint is TOTPAR 6. The record identifies 12 outcome measures overall. Testing or interpreting many outcomes can raise a multiplicity issue: when many comparisons are considered, the chance of a seemingly notable result arising by chance can increase. This is a general statistical concern, not a claim that a particular result in this study is spurious.

The registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting secondary outcomes. It also reports 0 analyses in the analysis listing. Consequently, the record does not provide enough information to assess which comparisons were formally tested, whether all planned outcomes were reported, or how any multiple-testing concerns were handled.

The primary outcome description states that last observation carried forward (LOCF) was used for imputed values and that all subjects were included in both the IIT and PP populations for analysis. LOCF carries a participant’s last observed value forward to fill a later missing value. In general, this approach can be misleading if the unobserved outcome would have changed over time, so the handling and amount of missing data matter. The registry does not report how many values were missing, why they were missing, or sensitivity analyses using other assumptions.

The record uses the terms IIT and PP but does not define them in detail or report population-specific results. It says all subjects were included in both populations, but does not explain how that statement was applied to each endpoint. These gaps limit assessment of the analysis populations and the robustness of the reported estimates.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry reports 0 serious adverse events among the 41 participants at risk in the XPF-001 arm and 0 among the 20 participants at risk in the placebo arm. These are the serious-event counts recorded for the listed groups. They do not show that no adverse events of any kind occurred, and they do not provide a comparative statistical analysis of safety.

The record also lists other adverse events affecting 16 participants in the XPF-001 group and 4 in the placebo group. Those are separate from the serious adverse event figures and should not be conflated with them. The registry does not provide detailed event descriptions in the listed serious-event terms, which are empty. Death counts are not reported in the registry record.

Zero recorded serious adverse events in the groups is a description of the posted safety data. It is not proof that the risk of serious events is absent, and the record does not report enough detail to characterize event timing, severity beyond the serious classification, or relatedness to treatment.

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

The posted results show arm-specific estimates for the primary pain-relief measure. The XPF-001 least-squares mean is 4.37, and the placebo least-squares mean is 2.45. The registry states that higher TOTPAR 6 scores indicate more pain relief. These values describe the observed estimates for the two arms; they are not themselves an estimate of the difference between treatments.

The 95% confidence intervals provide information about uncertainty in each arm’s mean. They do not provide the uncertainty around a treatment contrast. The registry record does not report that contrast, a p-value for the primary comparison, or enough statistical detail to reconstruct them. It is therefore not possible to determine from the posted results alone whether the between-arm difference was statistically distinguishable from no difference, or how precisely such a difference was estimated.

The study is described as a Phase 2 proof-of-concept trial, and the registry identifies a randomized, placebo-controlled design. Those features describe the study’s purpose and structure. They do not remove the limitations of incomplete comparative reporting. Nor do the group estimates, on their own, establish how results would apply outside the people and setting studied. The registry identifies the trial as single-center and does not report further information on eligibility or participant characteristics in the record.

The safety entries report no serious adverse events in either arm as recorded, while other adverse events are listed separately. The absence of recorded serious events in these groups should not be read as proof of no serious-event risk. Overall, the registry supports a descriptive account of arm-level results and safety counts. It does not contain the comparative statistical results needed to make a precise claim about the treatment effect.

13. Why This Trial Matters Statistically

This study illustrates why a randomized design and a reported treatment comparison are both important for statistical interpretation. Random assignment supports a structured comparison between groups, but the analysis still needs to report the contrast of interest and its uncertainty. Here, the registry gives arm-specific least-squares means and confidence intervals for TOTPAR 6, while a comparative estimate and inferential test are not reported in the registry record.

The endpoint also illustrates how a clinical measure can summarize repeated observations. TOTPAR 6 combines pain-relief ratings across time into one measure, allowing the outcome to represent the course of relief during the post-dose period rather than a single rating. Understanding its construction helps clarify what the score means, but does not resolve the missing details about the statistical model or treatment contrast.

The record distinguishes a planning calculation from observed trial results. It describes a design-stage power calculation based on published data, while the reported group means are estimates from the trial. Planning power does not substitute for a confidence interval or test of the observed treatment comparison. Likewise, hypothetical sample-size illustrations are planning tools, not evidence that a treatment effect has been demonstrated.

Finally, the record lists multiple secondary measures, but does not report their analyses or explain how multiplicity was handled. This makes it difficult to assess the breadth of the reported evidence. These features make the trial statistically informative as an example of how endpoint definitions, missing-data methods, planning assumptions, and transparent comparative reporting all shape interpretation.

14. 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 most important limitation for interpreting efficacy is that the registry reports arm-specific primary outcome estimates but no comparative treatment estimate or inferential test. It does not give a confidence interval for the difference, a p-value, or the details of the model underlying the least-squares means. As a result, the precision of the treatment contrast cannot be assessed from the registry record.

The record does not describe the allocation sequence, concealment procedures, masking roles, participant eligibility criteria, or baseline characteristics. Although the study is identified as randomized, quadruple-masked, and single-center, those labels do not supply the omitted procedural and population details. The actual administered dose and other treatment-exposure details are also not reported in the registry record.

The primary outcome description states that LOCF was used, but the amount and pattern of missing data are not reported. There is no reported sensitivity analysis to show how alternative assumptions about missing outcomes might affect the results. The registry’s statement about IIT and PP populations is not accompanied by definitions or separate population-specific results.

The registry lists secondary outcomes but reports 0 analyses. It does not explain multiplicity handling or identify a hierarchy for interpreting those outcomes. For safety, serious-event counts are listed as zero in the two groups, but deaths are not reported in the registry record and event details are limited. These reporting gaps constrain assessment of both efficacy and safety; they do not establish that unreported events or analyses did not occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of XPF-001 to Treat Pain Following Wisdom Tooth Extraction — NCT00954356.
• Registry record last updated 2012-07-16; status last verified 2012-07.
• Results first posted 2012-06-29.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT00954356 is a completed Phase 2, single-center, randomized, double-blind, placebo-controlled, parallel-group study of a single oral dose of XPF-001 for pain after wisdom tooth extraction. The registry reports enrollment of 61 and lists 41 participants in the XPF-001 outcome group and 20 in placebo.

The primary endpoint was TOTPAR 6, a time-based summary of pain-relief ratings during the 6 hours after dosing. The reported least-squares means are 4.37 for XPF-001 and 2.45 for placebo, with arm-specific 95% confidence intervals of 2.79 to 5.96 and 0.182 to 4.72, respectively. A comparative estimate and test are not reported in the registry record.

The record describes LOCF for imputed values and reports no serious adverse events in either listed group. It does not report death counts, detailed comparative analyses, or the statistical model used for the primary endpoint.