Study to Evaluate the Analgesic Efficacy of 28 Days' Oral Administration of AZD2066 Compared With Placebo in Patients With Painful Diabetic Neuropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Analgesic Efficacy of 28 Days' Oral Administration of AZD2066 Compared With Placebo in Patients With Painful Diabetic Neuropathy (NCT00857623), a randomized phase 2 study. The primary outcome is Change in Mean Numerical Rating Scale (NRS) Score From Baseline to Last 5 Days of Treatment.

2. Clinical Question

3. Trial Design

This was a Phase IIa, randomized, double-blind, parallel-group, multi-centre study comparing AZD2066 with placebo in patients with painful diabetic neuropathy. Quadruple masking is also recorded in the registry. The study is listed as completed, with enrollment of 127. The registry gives a start date of 2009-02 and primary completion in 2009-08.

The treatment period was 28 days. The primary outcome used a baseline period and a treatment-period measure: mean pain intensity over the 5-day baseline period was compared with the mean over the last 5 days on treatment. The posted primary outcome was analyzed in the Per Protocol population. The registry reports 46 participants for the AZD2066 primary outcome and 51 for placebo. Those outcome-specific figures should not be confused with the overall enrollment.

The record lists AZD2066 and placebo as drug interventions, but the arm descriptions are empty. Dose, detailed eligibility criteria, adherence requirements, and reasons for exclusion from the Per Protocol population are not reported in the registry record. The trial's original sample-size justification and the planned statistical analysis details are also not reported in the registry record. The posted results include outcome summaries and safety counts, but no reported secondary analyses are listed. These omissions limit reconstruction of the design and analysis beyond the information explicitly recorded.

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 study consisted of a 42-day enrollment phase (including washout and baseline period), a 28-day treatment phase (10-day inpatient and 18-day outpatient) where patients were randomized to AZD2066 or placebo, and a 7-day follow-up phase. Patients randomized to treatment with AZD2066 received 12 mg from Days 1 to 4 and 18 mg from Days 5 to 28.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per Protocol population (PP)

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 Change in Mean Numerical Rating Scale (NRS) Score From Baseline to Last 5 Days of Treatment, measured over From baseline to day 28.

The primary endpoint is the change in mean NRS pain score from baseline to the last 5 days of treatment, with the outcome timeframe described as baseline to day 28. It summarizes average pain intensity over specified periods rather than relying on a single pain rating. The NRS is a continuous score on a 0–10 scale: lower values represent less reported pain, and the registry defines 0 as no pain and 10 as the worst pain imaginable.

Repeated ratings can reflect variation in pain over time. Averaging ratings across the baseline and treatment periods is intended to provide a period-level measure for comparison. The endpoint is clinically relevant to the trial question because the study aimed to evaluate analgesic efficacy, and the NRS directly records participants' pain intensity. It does not, by itself, capture every aspect of the pain experience or the effect of pain on daily activity; other listed outcomes address measures such as pain interference and global impression.

The registry reports least-squares means and standard errors for the primary outcome in the Per Protocol population. It does not describe the model used to obtain the least-squares means, so the adjustment factors and detailed modeling assumptions are not reported in the registry record. The endpoint should therefore be interpreted as the posted summary measure, not as a fully specified account of the analysis procedure.

7. Results Posted in the Registry

• AZD2066: mean -2.33 versus -2.52 on control; difference 0.19 (95% CI -0.82 to 1.20), standardized effect d = 0.07; z-test p = 0.713.

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.

Daily Numerical Rating Scale (NRS) Pain Scores and Change From Baseline Over Time to Day 28.

• 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:
  • AZD2066: mean -2.30 versus -2.50 on control; difference 0.20 (95% CI -0.70 to 1.10), standardized effect d = 0.09; z-test p = 0.662.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZD2066 and the control. The interval gives the range of effects that remain compatible with the data.

Number of Patients With >=30% Reduction From Baseline in Numerical Rating Scale (NRS) Pain Intensity Score at Day 28

• 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:
  • AZD2066: 50.0% (23/46) versus 49.0% (25/51) on control; risk difference 1.0 percentage points (95% CI -18.9 to 20.9), risk ratio 1.02 (0.68–1.53); unadjusted two-proportion z-test p = 0.923.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZD2066 and the control. The interval gives the range of effects that remain compatible with the data.

Number of Patients With >=50% Reduction From Baseline in Numerical Rating Scale (NRS) Pain Intensity Score at Day 28

• 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:
  • AZD2066: 32.6% (15/46) versus 29.4% (15/51) on control; risk difference 3.2 percentage points (95% CI -15.2 to 21.6), risk ratio 1.11 (0.61–2.01); unadjusted two-proportion z-test p = 0.734.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZD2066 and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists a range of secondary outcomes that complement the primary mean pain score. These include pain scores over time, threshold reductions in NRS pain, patient global impression, and measures of sensory pain, affective pain, severity, and interference. The posted results include numerical summaries for daily pain scores and for the two threshold outcomes, but no reported analyses are listed. Results for the other listed secondary outcomes are not reported in the registry record.

Across the available secondary summaries, the estimates do not create a clear, consistent pattern of separation that would overturn the primary interpretation. Continuous pain-score summaries and threshold-based outcomes describe different features of response. A mean change uses the amount of change across the group, whereas a threshold outcome classifies participants according to whether a stated reduction was reached. Agreement or disagreement between these measures can be informative, but neither measure alone resolves the uncertainty in the primary comparison.

Secondary outcomes are useful for understanding whether a primary result is accompanied by changes in other dimensions of pain or patient experience. Their interpretation is limited when many outcomes are examined and the registry does not report a prespecified testing hierarchy or adjustment for multiplicity. Unadjusted findings have a higher risk of appearing noteworthy by chance when considered among multiple comparisons. They therefore carry less evidential weight than a clearly prespecified primary analysis, particularly when the registry does not provide adjusted analyses or a detailed statistical plan.

The missing secondary analysis details also restrict interpretation. The registry does not report whether the secondary outcomes used the same population as the primary outcome, how missing observations were handled, or what model was applied to repeated measurements. These results are best treated as descriptive context for the main endpoint, not as independent confirmation of a treatment effect.

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

• Daily Numerical Rating Scale (NRS) Pain Scores and Change From Baseline Over Time to Day 28.
• Number of Patients With >=30% Reduction From Baseline in Numerical Rating Scale (NRS) Pain Intensity Score at Day 28
• Number of Patients With >=50% Reduction From Baseline in Numerical Rating Scale (NRS) Pain Intensity Score at Day 28
• Number of Patients With Patient Global Impression of Change (PGIC) Score of at Least "Much Improved" at Day 28.
• Change in McGill Pain Questionnaire Short Form (MPQ-SF) Sensory Index From Baseline to Day 28.
• Change in McGill Pain Questionnaire Short Form (MPQ-SF) Affective Index From Baseline to Day 28.
• Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Severity From Baseline to Day 28.
• Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Interference From Baseline to Day 28.

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: each participant's outcome is a change in NRS score, and the registry summarizes the group results using least-squares means. A mean describes the average outcome in a group. A least-squares mean is generally a model-based group estimate, but the registry record does not report the model specification, covariates, or other adjustment details. It is therefore possible to describe the posted estimates, but not to reconstruct the model that produced them.

The primary summaries include a standard error for each least-squares mean. A standard error describes the uncertainty in an estimated mean, rather than the spread of individual participants' scores. The registry reports standard errors of 0.37 for AZD2066 and 0.36 for placebo. These values help characterize uncertainty in the group estimates; they do not show the range of individual pain changes.

A group difference is a direct way to express the comparison of interest. The unadjusted recalculation from posted summaries gives a mean difference of 0.19 for AZD2066 compared with placebo. The direction depends on which group is subtracted from which, so it should be read together with the stated comparison. The recalculated p-value is 0.713. A p-value describes how compatible the observed data are with a null model of no group difference, under the assumptions used for the calculation. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect.

The confidence interval adds information beyond the point estimate by showing a range of values compatible with the data and the calculation's assumptions. For the primary comparison, the interval spans values on both sides of zero. That means the posted summary statistics do not precisely distinguish a difference favoring one group from a difference favoring the other. The interval is not a guarantee that the true effect lies within its limits; its usual interpretation depends on the statistical method and assumptions.

Some posted comparisons are recalculated from summary statistics rather than taken from reported analyses. They are simple, unadjusted comparisons. They do not account for covariates, the trial's allocation process beyond the stated randomized design, or any model that may have been used in a sponsor analysis. The registry lists no reported analyses for the secondary outcomes, and it does not describe a detailed statistical plan. The registry record does not report whether an interim analysis was planned or conducted.

For continuous outcomes, variation among participants matters to the precision of a group comparison. More variable outcomes generally make it harder to estimate a group difference precisely. For binary outcomes, such as reaching a stated percentage reduction in pain, the comparison is based on whether the outcome occurred. These outcomes discard some information about the size of each participant's change: a participant just meeting a threshold and one with a larger reduction both count as meeting it. Threshold results can therefore tell a different, less detailed part of the story than a continuous score.

Over-dispersion is a general concern when count data vary more than a model's assumed distribution allows. If present and ignored, uncertainty can be understated. The posted primary endpoint is continuous, not a count outcome, and the registry does not report an over-dispersion assessment for this trial. The listed secondary threshold outcomes are binary, not count outcomes; their posted summaries do not establish that an over-dispersion issue was evaluated.

The primary analysis population is described as Per Protocol. In general, a Per Protocol analysis focuses on participants who meet specified adherence or eligibility conditions after randomization. The exact conditions used in this trial, the numbers excluded for each reason, and any comparison with an intention-to-treat analysis are not reported in the registry record. Such choices matter because excluding participants after randomization can affect how well the groups remain comparable.

Multiplicity arises when several outcomes or comparisons are examined. Even when each individual test uses a conventional significance threshold, examining multiple tests increases the chance of at least one apparently notable result by chance. The record lists multiple secondary outcomes but does not report a multiplicity adjustment or a hierarchy for interpreting them. The secondary p-values calculated from posted summaries are unadjusted and should not be treated as confirmatory evidence. More generally, the absence of a reported adjustment does not establish what procedures were used outside the registry record.

11. Confidence Intervals and Precision

The primary comparison has an estimated mean difference of 0.19, but its confidence interval spans values below and above zero. This is an important distinction: the point estimate gives one value for the group contrast, while the interval conveys that the estimate is uncertain. Because the interval includes zero, the data are compatible with no group difference under the calculation's assumptions. Its span also indicates that the result does not tightly pin down the direction or magnitude of a possible difference.

The standard errors for the primary group estimates are 0.37 for AZD2066 and 0.36 for placebo. These quantify uncertainty in the estimated group means, not variation among individual participants. The registry provides no confidence limits for the two group means themselves, but it does give a confidence interval for the recalculated mean difference. The unadjusted p-value of 0.713 is consistent with the interval's lack of a clear separation from zero, but the interval is more informative about the range of effects compatible with the data.

A confidence interval is not a range containing a fixed proportion of individual participants' outcomes. It is an interval procedure that, under its assumptions, would cover the true parameter at a stated rate over repeated studies. The exact method used for the recalculated interval is not a reported sponsor analysis; it is an unadjusted calculation from the posted summary statistics. The registry does not report an adjusted interval for the primary comparison.

Precision is limited by the information in the analyzed groups and by outcome variability. The posted means are close, but closeness of estimates does not prove equivalence. A narrow interval around zero could support a more precise statement about small differences; the interval in this result remains compatible with a broader range. Thus, the evidence is inconclusive about the direction and magnitude of the treatment contrast rather than demonstrating that the treatments have identical effects.

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 illustrations express required sample size as participants per arm for the continuous and binary outcomes in this trial. They are not totals across arms and are not total event counts. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They use the stated fraction of the observed effect as the effect to detect. The registry does not report the trial's original design assumptions or sample-size justification.

The 80% power column describes the number of participants per arm that a hypothetical study would need, under those planning assumptions, to have an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column uses a higher chance of detection and therefore requires more participants per arm under the same assumptions. For the primary endpoint, planning for 100% of the observed effect gives 2,810 participants per arm for 80% power and 3,762 participants per arm for 90% power.

The illustrations also consider smaller fractions of the observed effect. Smaller effects are harder to distinguish from random variation, so they require more participants to reach the same target power. For example, the displayed planning estimates increase when the assumed effect is 75% or 50% of the observed effect. These are hypothetical design calculations, not evidence about what the completed trial could or could not detect under its actual design. They are not observed power.

A sample-size curve conveys the same general relationship: as the effect to be detected becomes smaller, the required sample size rises. The curve should be interpreted in light of the stated planning assumptions and the observed effect used as its reference, rather than as a forecast of the results of a future study. The original trial's own planning assumptions are 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 = 0.190; pooled standard deviation σ = 2.542.
2. n = 2 × (1.96 + 0.842)² × 2.542² / 0.190² = 2,809.8, rounded up to 2,810 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 <- 0.19                      # observed difference in means
sigma <- 2.54199051718799                     # 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(857623)
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 = 2,810 (80% power), 3,762 (90% power)
 75% of observed effect: n per arm = 4,996 (80% power), 6,688 (90% power)
 50% of observed effect: n per arm = 11,240 (80% power), 15,047 (90% power)
power.t.test: 2810.8 
Simulated power at n = 2,810 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. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary endpoint. Testing or examining many outcomes creates a multiplicity issue: the chance of at least one apparently unusual result can increase as more comparisons are considered. The registry record does not report a multiplicity adjustment, a testing hierarchy, or which secondary outcomes, if any, were intended to support confirmatory conclusions. The available secondary comparisons are unadjusted recalculations from posted summaries, so they should be interpreted cautiously rather than as definitive tests.

Missing-data handling is not reported in the registry record. The record does not state how participants with incomplete NRS assessments were handled, whether any values were imputed, or whether sensitivity analyses were performed. It also does not provide a participant flow explaining the relationship between the enrollment of 127 and the populations contributing to each posted outcome.

The primary endpoint is reported for the Per Protocol population. The criteria defining that population, the number and reasons for exclusions after randomization, and any results from an intention-to-treat analysis are not reported in the registry record. A Per Protocol analysis may differ from an analysis that retains participants according to randomized assignment; without details about the exclusions and missing observations, the effect of population selection cannot be assessed.

The registry record also does not report the full statistical analysis plan, model specifications, interim-analysis procedures, or the original sample-size assumptions. These omissions do not establish that such procedures were absent; they mean that they cannot be evaluated from the registry record. Interpretation is consequently limited to the posted outcomes and the unadjusted recalculations based on their summary statistics.

15. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hip fracture (1.6%), cardiac failure congestive; myocardial infarction (1.5%).

The registry safety summaries report participants at risk and the number affected by serious and other adverse events. For serious adverse events, 1 participant was affected in the AZD2066 group, with 62 at risk, and 1 in the placebo group, with 65 at risk. For other adverse events, 19 participants were affected in the AZD2066 group and 20 in the placebo group, using the same respective numbers at risk.

The registry also lists serious-event terms with percentages: hip fracture at 1.6%, and cardiac failure congestive; myocardial infarction at 1.5%. The record does not give enough context in this summary to assign these terms to a particular treatment group or to interpret them as comparative rates. Deaths are not reported in the posted safety summary.

These figures describe events recorded during the trial; they do not establish that an event was caused by treatment. The numbers at risk in the safety summaries differ from the primary endpoint analysis populations, so safety and efficacy denominators should not be treated as the same. The registry record does not provide event-level timing, severity details beyond the serious-event classification, or a comparative safety analysis.

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

The trial addresses a specific question: how the mean NRS pain score changed over the 28-day treatment period for AZD2066 compared with placebo among patients with painful diabetic neuropathy. The posted primary summaries show decreases from baseline in both groups. The unadjusted estimated difference is 0.19, with a confidence interval that crosses zero and an unadjusted p-value of 0.713. The result therefore does not provide precise evidence of a difference between groups on the primary endpoint.

This does not show that the treatments are equivalent, and it does not prove that no effect exists. A non-significant result can arise when a true difference is small, when the estimate is imprecise, or when the data do not clearly distinguish a difference from no difference. The confidence interval's breadth is relevant: it leaves uncertainty about the possible size and direction of the group contrast. No equivalence margin or equivalence analysis is reported in the registry record.

The outcome is a measure of reported pain intensity, not a comprehensive measure of health or functioning. Other outcomes listed in the registry concern pain interference, global impression, and pain qualities, but the record does not report results for all of them. The trial's findings should not be extended to conditions, treatment durations, doses, or populations not described in the registry record.

Interpretation is also constrained by the use of the Per Protocol population for the primary endpoint and by missing details on exclusions and missing data. The posted safety counts describe adverse events observed in the trial but do not establish causation or provide a complete comparative safety assessment. Taken together, the registry results describe the observed summaries and their uncertainty; they do not support a broad conclusion about treatment beyond the study's recorded population, outcomes, and period.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate, a p-value, and a confidence interval answer different questions. The mean difference gives the estimated direction and size of the primary contrast. The p-value describes compatibility with a null model under the calculation's assumptions. The confidence interval shows that the estimated contrast remains uncertain across values on either side of zero. Reading only the point estimate or only the p-value would miss that uncertainty.

It also highlights the distinction between a continuous endpoint and responder thresholds. Mean NRS change uses the magnitude of score changes, while threshold outcomes classify whether a participant meets a specified reduction. Those approaches can complement one another, but they do not measure precisely the same feature of the outcome. Multiple secondary outcomes also raise the importance of knowing the planned testing hierarchy and any multiplicity adjustment.

The registry gives a clear primary population label and outcome summaries, but leaves important methodological details unreported: the model, handling of missing data, Per Protocol criteria, and original design assumptions. Such details affect how readers assess potential bias and reproduce the analysis. Finally, planning illustrations based on the observed effect help explain the relationship between effect size and sample size, but they cannot substitute for the trial's original design justification or turn an inconclusive result into evidence of absence.

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 does not report the AZD2066 dose, detailed arm descriptions, eligibility criteria, or the criteria used to define the Per Protocol population. These omissions make it difficult to judge how representative the analyzed participants were of those randomized or how the treatment was implemented.

The primary endpoint is presented as a least-squares mean, but the model specification and any adjustment factors are not reported. The method used to handle missing outcome measurements, protocol deviations, or treatment discontinuation is also not reported in the registry record. No intention-to-treat result is listed, so the effect of analyzing the Per Protocol population cannot be compared with a result retaining participants by randomized assignment.

The registry lists multiple secondary outcomes, but results are posted for only some of them, and no reported analyses are listed. A prespecified hierarchy, multiplicity adjustment, and full analysis plan are not reported. The posted recalculations are unadjusted and should not be treated as a substitute for a complete sponsor analysis.

The safety summary gives affected counts and numbers at risk but does not provide detailed event timing, attribution, or a comparative safety analysis. Deaths are not reported. These limitations are specific to the information available in the registry record and do not establish what analyses or details may exist outside it.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Study to Evaluate the Analgesic Efficacy of 28 Days' Oral Administration of AZD2066 Compared With Placebo in Patients With Painful Diabetic Neuropathy — NCT00857623.
• Registry record last updated 2012-11-12; status last verified 2012-11.
• Results first posted 2012-10-29.
• 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.

22. Record Summary

The registry record describes a completed, randomized, quadruple-masked, parallel-group Phase IIa study of oral AZD2066 versus placebo in patients with painful diabetic neuropathy. Enrollment was 127, and treatment lasted 28 days. The primary outcome was change in mean NRS pain score from baseline to the last 5 days of treatment in the Per Protocol population.

The posted primary summaries show mean decreases in both groups. The unadjusted recalculated difference is 0.19, with a confidence interval spanning zero and an unadjusted p-value of 0.713. The result is imprecise and does not establish a difference between groups. Some secondary and safety summaries are posted, but the registry does not report several analysis details needed for fuller evaluation, including missing-data methods, the primary model specification, and multiplicity procedures.