Study to Investigate the Analgesic Efficacy of a Single Dose of AZD1386: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Investigate the Analgesic Efficacy of a Single Dose of AZD1386 (NCT00672646), a randomized phase 2 study. The primary outcome is Sum of Pain Intensity Difference in Percent (SPID%).

2. Clinical Question

The study was designed around acute pain following a specific surgical procedure. Its primary endpoint, Sum of Pain Intensity Difference in Percent (SPID%), combines pain-intensity changes measured over time, with assessments weighted according to the time since the previous assessment. The registry describes higher values as indicating a better effect and lower values as indicating a poorer effect.

The clinical question is therefore narrower than whether AZD1386 relieves pain in general. It concerns the posted pain measure in this study setting and over its specified observation period. The record also lists time to first perceptible pain relief, time to first meaningful pain relief, and pain ratings at rescue intake among the secondary outcomes. It does not report results for those secondary outcomes here, nor does it provide an estimated treatment contrast, uncertainty interval, or test of the primary comparison.

3. Trial Design

This was a Phase 2, randomized, triple-masked, parallel-group study sponsored by AstraZeneca. It is titled as an investigation of the analgesic efficacy of a single dose of AZD1386. The registry describes the study as completed, with enrollment of 103. The recorded start was 2008-04 and primary completion was 2008-06.

The three listed groups were AZD1386, naproxen, and placebo. Placebo is described as matching AZD1386. The record identifies naproxen as a control and says acetaminophen could be used as rescue medication if additional pain relief was needed. It does not report the dose or administration schedule for the study drugs, how randomization was generated, or the allocation ratio. The arm counts displayed with the primary endpoint are 40 for AZD1386, 23 for naproxen, and 40 for placebo.

Triple masking indicates that the registry classifies the study as masked at three levels, but it does not identify which roles were masked or explain the practical masking procedures. The parallel model indicates that participants were assigned to groups rather than receiving a sequence of treatments, but details of the conduct and follow-up are not reported in the registry record.

The registry lists the primary outcome as SPID% over the period from administration of the investigational product until the first administration of rescue analgesic or a maximum of 8 hours. It also lists five secondary outcomes: pain intensity measured with a visual analogue scale, time to first perceptible pain relief, time to first meaningful pain relief, and pain ratings at rescue intake, including pain on jaw movement. The record lists six outcome measures overall, but does not include analyses for them. Details of the sample-size justification and other design assumptions 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.

Before assignment: Screening for eligibility prior to the residential day, and selecting the patients that request pain relief, due to pain from the dental surgical area, within 6 hours after the end of the administration of the local anaesthetic.

Overall Study

Reasons for not completing this period:

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 Difference in Percent (SPID%), measured over from the start of administration of the investigational product up to the time of first administration of rescue analgesic or up to a maximum of 8 hours.

The primary endpoint is Sum of Pain Intensity Difference in Percent (SPID%). It summarizes pain-intensity differences across repeated assessments during the stated observation period. In the registry description, each difference is weighted according to the elapsed time since the previous pain assessment; the first post-dose assessment is referenced to administration of the investigational product. This weighting makes the summary reflect both the size of the recorded changes and the time intervals over which they apply.

Pain intensity was assessed with a visual analogue scale, described in the record as ranging from 0 to 100 mm. The endpoint is expressed as a percentage of pain-intensity change multiplied by hours. The registry describes higher SPID% values as indicating a better effect and lower values as indicating a poorer effect. This direction is important when reading the arm summaries, but it does not by itself establish that a difference between arms is statistically reliable or clinically important.

A summary endpoint can be useful when repeated measurements are collected over a defined period: it condenses a sequence of assessments into one measure for each participant. Here, the observation period ends at rescue analgesic use or at the maximum of 8 hours, whichever comes first. Rescue use may therefore affect how long an individual contributes pain assessments to this endpoint. The record does not explain how observations after rescue were handled, how missing assessments were treated, or whether an adjusted analysis was planned. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents a median and full range for the primary endpoint in each arm. These are descriptive summaries. They help show the central value and observed spread of the posted data, but they are not a substitute for a direct comparison between groups. No inferential analysis of the primary endpoint is reported in the registry record.

What does a median show?

A median is a measure of the center of a distribution. It is the point that divides ordered observations into a lower and an upper portion. Unlike a mean, it is not determined by adding all values and dividing by the number of observations. It can be useful when data are skewed or include extreme observations, although the registry does not report why the median was selected for this endpoint.

The endpoint summaries are AZD1386 median 35.5, naproxen median 171.8, and placebo median -7.5. These summarize each arm separately. Comparing their ordering can describe the posted pattern, but a difference between medians is not itself an estimate with uncertainty. The record does not report a test or interval for a contrast between arms.

How should the full ranges be read?

A full range gives the lowest and highest observed values in the relevant group. The posted ranges are -156.4 to 603.7 for AZD1386, -723.8 to 709.8 for naproxen, and -106.5 to 588.7 for placebo. A range is sensitive to extreme observations and does not show how densely values are distributed between its endpoints. It is not a confidence interval. A confidence interval, in general, is an interval designed to express uncertainty about an estimated quantity under specified statistical assumptions. No confidence interval for a treatment contrast is reported.

The ranges extend on both sides of zero. The registry’s endpoint description says higher values indicate a better effect and lower values a poorer effect. That direction describes how to read SPID%; it does not make the range endpoints evidence for or against a treatment effect. In particular, the posted ranges are not a test of whether the arm medians differ.

Why does the endpoint use repeated assessments?

SPID% combines pain-intensity differences from repeated assessments, weighting each difference by the time since the preceding assessment. In general, weighting by elapsed time can account for the fact that assessments are not simply isolated readings: a recorded level can represent a period until the next measurement. The endpoint therefore summarizes a trajectory over its defined observation period rather than reporting only one pain rating.

The record defines that period as beginning with administration and ending at the first administration of rescue analgesic or a maximum of 8 hours. Participants who use rescue medication may have a shorter observed period under this definition. How rescue use was incorporated into analysis, and whether its timing was compared between groups, is not reported in the registry record.

What is not available for inference?

A statistical comparison normally needs an estimate of the between-group effect and some measure of its uncertainty, together with an account of the analysis used. The registry record does not report a treatment contrast, confidence interval, p-value, or statistical test for SPID%. The record lists zero analyses. It also does not say whether the primary analysis adjusted for baseline pain, other covariates, or features of the repeated assessments.

In general, statistical significance and clinical importance address different questions. A significance test evaluates compatibility with a specified statistical model and null hypothesis; clinical importance concerns the relevance of an effect in the study setting. Neither can be assessed from separate arm medians and full ranges alone. The record does not provide an interpretation threshold for SPID% or a minimally important difference.

What do the planning illustrations represent?

The sample-size section contains planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such values are hypothetical planning calculations, not the study’s observed power, not evidence that the trial was designed using those assumptions, and not a replacement for the missing comparative analysis. The record does not report the trial’s own sample-size justification. No planning values are restated.

Over-dispersion is a general statistical concern when observed variation exceeds what a chosen model assumes. In general, a model that understates variation can produce uncertainty estimates that are too narrow. The registry does not report a model for this endpoint or any assessment of over-dispersion, so it is not possible to say whether this issue arose in the trial analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, SPID%, and five secondary outcomes: pain intensity by visual analogue scale, time to first perceptible pain relief, time to first meaningful pain relief, pain intensity at rescue intake, and pain on jaw movement at rescue intake. It reports six outcome measures overall but does not provide analyses for them. The results for the secondary outcomes are therefore not available in this record.

When a study examines multiple outcomes or comparisons, there is a general multiplicity issue: the chance of obtaining at least one apparently notable result can change as the number of analyses increases. A statistical plan may address this through a prespecified testing sequence or adjustment, but the record does not report whether any such approach was planned or used. The multiplicity strategy is not reported in the registry record.

The registry also does not report how missing pain assessments were handled, whether participants with incomplete assessments were included, or how rescue medication affected endpoint calculation. The primary measure’s observation window ends at rescue use or a maximum of 8 hours, but no missing-data or rescue-handling method is described.

The analysis population is not reported in the registry record. Although the study enrollment is 103 and arm-specific primary endpoint counts are displayed, the record does not identify whether these counts represent all randomized participants, participants who received treatment, or a subset with evaluable endpoint data. It also does not provide participant flow or reasons for any difference between enrollment and the displayed counts. These omissions limit assessment of how the posted summaries relate to the randomized groups.

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 adverse-event table reports zero serious adverse events among participants at risk in each arm: 40 for AZD1386, 23 for naproxen, and 40 for placebo. These figures describe the counts recorded in the posted safety data. They do not establish that the treatments have no serious risks, and they do not provide a comparative safety analysis.

The table also reports other adverse events affecting 4 participants in the AZD1386 group, 0 in the naproxen group, and 6 in the placebo group, with the same arm-specific numbers at risk. The registry record does not define the category of other adverse events or provide event-level details. These counts should not be read as rates calculated for a different follow-up period, since that period is not specified in the safety summary.

Death counts are not reported in the registry record. No serious-event terms are listed, and the serious-event counts are zero in all three groups. The absence of reported serious events in this table is a description of these posted data, not proof that no safety events occurred outside the recorded scope or that the groups are equivalent in safety.

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

The posted data show that the three arms had different median SPID% values, with naproxen highest, AZD1386 between naproxen and placebo, and placebo lowest. The endpoint description identifies higher values as better. These are descriptive findings from the registry record, and the full ranges show substantial observed spread within each arm.

The record does not report a statistical comparison or an uncertainty interval for differences between arms. It therefore does not show whether the descriptive ordering is compatible with chance variation under a specified statistical model, nor how precisely any treatment effect was estimated. The record also does not supply a threshold for interpreting the size of an SPID% difference as clinically important. For these reasons, the posted values alone do not establish that one study treatment was superior, equivalent, or inferior to another.

The result applies to a specific trial question: pain after impacted mandibular third molar extraction, assessed using a time-weighted pain-intensity summary until rescue analgesic use or a maximum of 8 hours. It should not be treated as a result for other pain conditions, other procedures, or longer-term outcomes. The study allowed acetaminophen rescue, but the record does not report rescue-use results or how rescue affected analysis.

The record lists secondary measures relating to pain intensity, time to relief, and pain at rescue intake, but does not report their analyses. It also does not describe missing-data methods, analysis populations, or a multiplicity strategy. These gaps leave important questions about the scope and robustness of the results unanswered.

In short, this registry entry gives arm-level descriptive summaries and safety counts. It does not provide enough inferential information to make a statistical conclusion about comparative analgesic efficacy. The planning illustrations are hypothetical calculations based on the observed effect, not observed power and not results of the trial’s own design process.

13. Why This Trial Matters Statistically

This study illustrates the difference between reporting outcomes by arm and reporting a treatment comparison. A table of arm-level medians and ranges can describe what was observed, but the central inferential question is usually about the contrast between groups and its uncertainty. Here, the record provides the separate summaries but not the comparison, leaving readers unable to assess its precision from the registry results.

It also highlights why the form of a summary matters. SPID% is built from repeated pain assessments and weights differences by elapsed time. The endpoint is intended to represent the course of pain over a defined period, rather than a single assessment. Its interpretation depends on the observation window and on how rescue use is handled; the latter details are not reported in the registry record.

The broad full ranges also emphasize that observed individual values can vary substantially within arms. A full range is useful for showing the extremes, but it is not an uncertainty interval for a group comparison. Readers should distinguish these descriptive quantities from confidence intervals and statistical tests, neither of which is reported for the primary comparison.

Finally, this record is a useful reminder that a completed study and a posted outcome summary do not necessarily provide a complete account of the analysis. The registry lists multiple outcomes, but no analyses. The analysis population, missing-data approach, multiplicity handling, and sample-size justification are not reported in the registry record. Those omissions affect how fully the trial’s results can be evaluated statistically, independently of the numerical values displayed.

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 main limitation for interpreting this particular trial record is the absence of a reported comparative analysis. The registry supplies arm-level medians and full ranges for SPID%, but no treatment contrasts, confidence intervals, p-values, or test results. The posted values therefore cannot establish statistical evidence for differences between groups.

The record does not report why the endpoint counts are 40 for AZD1386, 23 for naproxen, and 40 for placebo, or how they relate to the enrollment of 103. Participant flow, analysis populations, exclusions, and reasons for missing endpoint data are not described. The method used to handle incomplete pain assessments is also not reported in the registry record.

Although rescue acetaminophen was allowed and the primary observation period ended at rescue use or a maximum of 8 hours, the record does not report rescue-use counts, the handling of post-rescue data, or whether rescue use was considered in the comparative analysis. These details matter for understanding an endpoint whose observation window can end at different times for different participants.

The registry lists secondary outcomes but does not include their analyses. It does not report a multiplicity strategy, the statistical model, the sample-size justification, or whether interim analyses took place. The dose and detailed administration procedures are also not reported in the registry record. The adverse-event summary does not define other adverse events or report death counts. Together, these gaps constrain interpretation of efficacy, precision, safety, and the analysis process.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Investigate the Analgesic Efficacy of a Single Dose of AZD1386 — NCT00672646.
• Registry record last updated 2012-06-08; status last verified 2012-05.
• Results first posted 2012-06-08.
• 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

This completed Phase 2 study was randomized, triple-masked, and parallel-group, with enrollment of 103. It investigated a single dose of AZD1386 against placebo and naproxen in patients undergoing impacted mandibular third molar extraction. Acetaminophen was allowed as rescue medication.

The primary outcome was SPID%, summarizing pain-intensity differences from administration until rescue analgesic use or a maximum of 8 hours. The registry reports arm-specific medians and full ranges, but no comparative analyses. Five secondary outcomes are listed without reported analyses. The record also reports zero serious adverse events in each arm and other adverse-event counts of 4, 0, and 6 for AZD1386, naproxen, and placebo, respectively.

Important analysis details, including the analysis populations, missing-data methods, multiplicity strategy, and sample-size justification, are not reported in the registry record.