Effect on Structural Changes in Airways, Measured by MSCT, of Twice Daily 60mg AZD9668 for 12 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect on Structural Changes in Airways, Measured by MSCT, of Twice Daily 60mg AZD9668 for 12 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT01054170), a randomized phase 2 study. The primary outcome is AWT-Pi10 (Airway Wall Thickness of a Theoretical Airway With an Internal Perimeter of 10 mm).

2. Clinical Question

The trial was designed to assess structural changes in the airways rather than to answer every question about COPD symptoms, daily functioning, or longer-term clinical outcomes. Its primary endpoint was AWT-Pi10 at day 84, measured in millimetres. The endpoint represents airway wall thickness for a theoretical airway with an internal perimeter of 10 mm.

The posted primary comparison is a difference between the groups’ end-of-treatment least-squares means. It estimates the contrast in this particular imaging measure among participants included in the efficacy analysis for that outcome. It does not, by itself, establish whether any observed imaging difference corresponds to a change in symptoms or other outcomes important to patients. Such questions are not answered by the primary endpoint reported in the registry record.

The registry identifies COPD as the condition and adults with COPD as the population in the study description. Further eligibility details, including the precise diagnostic criteria and disease characteristics required for enrolment, are not reported in the registry record.

3. Trial Design

The registry describes a Phase II, randomized, double-blind, placebo-controlled, parallel-group, multicentre study. It lists quadruple masking; which specific groups or roles were masked is not reported in the registry record. The planned intervention was oral AZD9668 at 60mg twice daily, compared with placebo, over 12 weeks. The primary endpoint was measured after treatment at day 84.

Enrollment is listed as 52. The primary efficacy results include 17 participants in the AZD9668 group and 19 in the placebo group. These outcome-specific analysis counts are not a replacement for the registry’s enrollment figure: the primary analysis population is described as including participants who received at least one dose and had a baseline and at least one post-randomisation measurement for that outcome. The registry does not explain the difference between enrollment and the reported outcome analysis counts.

The study status is completed. The registry lists a start of 2010-01 and primary completion of 2010-11. The sponsor is AstraZeneca. The registry record does not report the original sample-size calculation, the assumptions used to plan enrollment, or whether interim analyses were planned or conducted. The planning illustrations based on the observed result are separate from those unreported design details.

The registry outcome description says participants were analysed by randomized treatment, but the sentence describing that approach is incomplete in the registry record. More detail about allocation procedures, centre-level methods, adherence, treatment discontinuation, and the handling of missing outcome measurements is not reported in the registry record. These omissions limit how fully the analysis and conduct can be reconstructed from the posted 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: Tiotropium maintenance therapy and reliever medication were commenced at screening, except for patients on inhaled corticosteroids (ICS, ICS/LABA) who were required to stop these at enrolment and commence on tiotropium and reliever medication at the same time. These patients received tiotropium for a period of at least 3 weeks before screening.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The efficacy analysis set for each outcome measure includes those patients who received at least one dose of investigational product and for whom a baseline and at least one post-randomisation measurement is available for that outcome measure. Patients were analysed by to randomised treatment in accordance with the intention to treat principle.

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 AWT-Pi10 (Airway Wall Thickness of a Theoretical Airway With an Internal Perimeter of 10 mm), measured over Measured after 12 weeks treatment (day 84).

The primary endpoint is AWT-Pi10, or airway wall thickness for a theoretical airway with an internal perimeter of 10 mm, measured in millimetres. The registry describes the primary result as the end-of-treatment least-squares mean after 12 weeks of treatment, at day 84. Airway wall thickness measured by multi-slice computed tomography (MSCT) is used as an imaging measure of structural change in the airways.

A standardized theoretical airway allows the reported measure to represent wall thickness at a specified internal perimeter, rather than relying on a single airway chosen from an individual scan. In general, a continuous imaging endpoint can capture gradations in a measured anatomical feature and can be compared between randomized groups. That makes it useful for asking whether the groups’ average imaging measurements differ at the end of treatment.

The endpoint is not itself a direct measure of symptoms, exacerbations, or how a participant feels or functions. Nor does the registry establish that a particular change in AWT-Pi10 would be clinically meaningful. AWT-Pi10 therefore addresses the trial’s structural-imaging question; interpretation beyond that question requires evidence that is not reported in the registry record.

7. Results Posted in the Registry

• AZD9668: mean 3.84 versus 3.83 on control; difference 0.01 (95% CI -0.04 to 0.06), standardized effect d = 0.12; z-test p = 0.711.

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.

5th Generation Wall Area Percentage

• 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 errors.
• Result:
  • AZD9668: mean 66.21 versus 65.94 on control; difference 0.27 (95% CI -0.44 to 0.98), standardized effect d = 0.25; z-test p = 0.455.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZD9668 and the control. The interval gives the range of effects that remain compatible with the data.

Air Trapping Index (ATI) on Expiratory Scans

• 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 errors.
• Result:
  • AZD9668: mean 54.56 versus 57.12 on control; difference -2.56 (95% CI -7.14 to 2.02), standardized effect d = -0.41; z-test p = 0.274.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZD9668 and the control. The interval gives the range of effects that remain compatible with the data.

Pre-bronchodilator Inspiratory Capacity (IC)

• 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 errors.
• Result:
  • AZD9668: mean 2.56 versus 2.39 on control; difference 0.17 (95% CI -0.26 to 0.60), standardized effect d = 0.23; z-test p = 0.434.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZD9668 and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes spanning airway structure, air trapping, and lung-function measures. The posted results include continuous measures assessed after 12 weeks. Across the reported secondary comparisons, the estimates vary in direction and scale, and their confidence intervals include zero. The registry lists 23 secondary outcomes, while posted numerical results are available for only a subset in the record. The remaining secondary results are not reported in the registry record.

The secondary outcomes provide context about other measurements collected during the study, but they do not replace the primary AWT-Pi10 comparison. The primary result concerns a specific measure of airway wall thickness; other imaging measures and physiological measures address related but distinct aspects of COPD. Similar or different patterns across these outcomes do not, by themselves, validate or overturn the primary result.

Unadjusted secondary results carry less weight because several outcomes are considered. In general, examining many endpoints increases the chance that some results appear unusual by chance, even when there is no underlying difference. A prespecified hierarchy or multiplicity adjustment can address that concern, but the registry record does not report an adjustment plan or a complete analysis hierarchy. Therefore, secondary p-values should be interpreted as exploratory rather than as stand-alone confirmatory evidence.

Some secondary outcomes have fewer participants contributing measurements than the primary endpoint. This can reduce precision and may make comparisons across endpoints difficult to interpret. The registry does not report why the outcome-specific analysis counts differ, how missing measurements were handled, or whether those differences were anticipated. Taken together, the secondary results offer a limited, incomplete view of related outcomes and should be considered alongside the primary analysis, not as independent proof of a treatment effect.

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

• 5th Generation Wall Area Percentage
• Air Trapping Index (ATI) on Expiratory Scans
• Pre-bronchodilator Inspiratory Capacity (IC)
• Pre-bronchodilator Total Lung Capacity (TLC)
• Pre-bronchodilator Functional Residual Capacity (FRC)
• Pre-bronchodilator Residual Volume (RV)
• Pre-bronchodilator Specific Airway Conductance (SGaw)
• Pre-bronchodilator Diffusion Capacity of Carbon Monoxide (DLco)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: AWT-Pi10 is measured in millimetres. The registry reports least-squares means and standard errors for each randomized group at the end of treatment. A least-squares mean is a model-based group mean; the registry record does not provide enough detail to describe the model or the covariates used. The reported difference compares the AZD9668 mean with the placebo mean.

What does the mean difference represent?

The posted estimate is 0.01 mm, calculated as the AZD9668 group mean minus the placebo group mean. A positive value means the reported mean is higher in the AZD9668 group; a negative value would mean it is lower. The direction alone does not establish whether a difference is important. The endpoint’s clinical interpretation depends on context, including what magnitude of change would be meaningful, and that threshold is not reported in the registry record.

How should the p-value be read?

The unadjusted p-value is 0.711. In general, a p-value describes how inconsistent the observed data are with a specified null hypothesis under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, nor is it a measure of the size or importance of a difference. The registry does not report the test’s full specification, so the posted p-value should be treated as the unadjusted result rather than as evidence about an undocumented analysis plan. The value does not cross the conventional significance level of 0.05 stated in the planning assumptions, but that alone does not show that the groups are equivalent.

What does the confidence interval add?

The confidence interval for the mean difference extends from -0.043 to 0.063. In general, a confidence interval communicates uncertainty around an estimate: values inside it are compatible with the data under the interval’s method and assumptions. Because this interval includes zero, it is consistent with no group difference as well as with differences in either direction. The confidence level and interval-construction method are not reported in the registry record, so they should not be inferred from the endpoints alone.

Why distinguish standard errors from standard deviations?

The group spreads reported for the primary means are standard errors, not standard deviations. A standard error describes uncertainty in an estimated mean; a standard deviation describes variation among individual measurements. They answer different questions and should not be interchanged. The registry lists standard errors of 0.021 for AZD9668 and 0.017 for placebo. The posted group means and standard errors do not provide a full account of individual-level variation or the distribution of measurements.

What does randomization contribute?

Random allocation is intended, in general, to make treatment groups comparable at the start of a trial with respect to measured and unmeasured characteristics. It supports interpreting a between-group contrast as an estimate of the effect of assignment under the study conditions, provided the trial’s conduct and analysis preserve the randomized comparison. The registry labels the study randomized and says participants were analysed by randomized treatment, but its analysis description is incomplete. Details of sequence generation, concealment, and departures from assigned treatment are not reported in the registry record.

What can be said about the recalculated planning illustrations?

The planning illustrations use the observed group contrast and an approximate pooled standard deviation derived from the posted standard errors. These are simple unadjusted recalculations, not the trial’s original design calculation. A standard deviation describes participant-level spread, while the standard errors describe uncertainty in group means. Because the spread is approximated from summary information, the resulting planning figures are illustrative rather than a replacement for a calculation based on individual-level data or a documented protocol plan. The registry does not report the original sample-size justification, statistical analysis plan, or any adjustment strategy.

In general, continuous-outcome analyses can also be affected by skewness, outliers, model specification, and missing observations. The registry record does not provide enough information to assess those features for AWT-Pi10. No inference about them should be made from the group means and standard errors alone.

11. Confidence Intervals and Precision

The primary estimate is a mean difference of 0.01 mm, with a confidence interval from -0.043 to 0.063. The interval crosses zero, so the posted data are compatible with a small difference in either direction as well as with no difference. The p-value is 0.711, which is consistent with the absence of strong statistical evidence against a no-difference hypothesis in this comparison.

Precision is about how narrowly the data locate the underlying group difference. A narrow interval allows a more constrained range of values than a wide interval, but whether that range is clinically important depends on a meaningful-change threshold. The registry does not report such a threshold for AWT-Pi10. It also does not report the confidence level or the method used to construct the interval, so these should not be assumed.

The primary analysis includes 17 participants in the AZD9668 group and 19 in the placebo group. The registry describes an outcome-specific efficacy set, requiring treatment exposure and available baseline and post-randomisation measurements. The size and handling of any missing outcome data are not described in sufficient detail to assess their impact on the interval.

The standard errors for the group means are 0.021 and 0.017. These quantify uncertainty in the estimated means, not the variability among individual participants. The interval for the between-group contrast is the more direct summary of uncertainty about the primary comparison. It does not establish equivalence, and the fact that zero lies within it does not eliminate the possibility of a clinically relevant difference. Judging that possibility requires both an appropriate meaningful-change threshold and a sufficiently precise estimate, neither of which is fully established by the registry record.

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 events. They are illustrations calculated from the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row considers detecting the stated fraction of the observed effect. The registry’s own original sample-size assumptions are not reported in the registry record.

For the primary endpoint, the illustration based on 100% of the observed effect gives 1,011 participants per arm for 80% power and 1,353 participants per arm for 90% power. The rows for 75% and 50% of the observed effect require progressively more participants per arm. These figures show how strongly planning estimates depend on the assumed effect size; they are not a reconstruction of the trial’s enrollment target or design rationale.

In general, power is the chance that a planned study will detect an effect of a specified size under its assumptions if that effect is present. The 80% column corresponds to a design targeting an 80% chance of detecting the stated effect, while the 90% column targets a higher chance. Smaller effects are harder to distinguish from random variation, so they require more participants under the same assumptions. This is not observed power: it is a planning calculation based on the observed result, not a measure of what the completed trial achieved.

Because the observed primary difference is used as the starting point, these illustrations can be especially sensitive to uncertainty in that estimate. They should be read as conditional planning examples, not as evidence that a future study would necessarily observe the same effect or need precisely these numbers.

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 = 0.010; pooled standard deviation σ = 0.080.
2. n = 2 × (1.96 + 0.842)² × 0.080² / 0.010² = 1,010.2, rounded up to 1,011 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 <- 0.00999999999999979                      # observed difference in means
sigma <- 0.0802184517427256                     # 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(1054170)
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 = 1,011 (80% power), 1,353 (90% power)
 75% of observed effect: n per arm = 1,796 (80% power), 2,405 (90% power)
 50% of observed effect: n per arm = 4,041 (80% power), 5,410 (90% power)
power.t.test: 1011.1 
Simulated power at n = 1,011 per arm: 0.799 (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 a primary endpoint and a range of secondary outcomes. When multiple outcomes are tested, the chance of at least one apparently notable result arising by chance can increase. In general, a prespecified testing sequence or an adjustment for multiplicity can help control that risk. The registry record does not report whether the trial used a multiplicity adjustment, a formal hierarchy among outcomes, or a prespecified approach to interpreting secondary results. The primary unadjusted p-value and the secondary unadjusted comparisons therefore should not be treated as though a documented family-wise testing strategy were available.

The registry reports 24 outcome measures and 23 posted secondary outcomes, but it lists zero analyses. The secondary outcomes with numerical results do not have reported analyses in the registry record. This does not establish that no analyses were conducted; it means that the analysis details are not available in the record. The original statistical analysis plan, including model specifications, covariates, missing-data procedures, and planned sensitivity analyses, is not reported in the registry record.

The efficacy population is described as including participants who received at least one dose and had baseline and at least one post-randomisation measurement for the outcome under consideration. That definition makes the analysis set outcome-specific. The record also says participants were analysed by randomized treatment, but the sentence is incomplete. It does not explain how participants with no post-randomisation measurement, treatment discontinuation, or protocol deviations were handled.

Missing data can affect both the estimate and its precision, especially if the likelihood of missingness is related to participant characteristics or outcomes. In general, excluding participants without an available measurement can change the composition of an analysis set. The registry does not provide enough information to assess whether missingness occurred, why it occurred, or whether its handling could have affected the results. These uncertainties limit assessment of the analysis population and the robustness of the posted findings.

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: post procedural complication (3.7%).

The registry lists serious adverse events for 0 of 25 participants at risk in the AZD9668 group and 1 of 27 participants at risk in the placebo group. These figures describe the recorded counts in the listed safety populations. They are not the same as the primary efficacy analysis counts, and the groups at risk should be read using their stated denominators.

The registry also lists a serious event term, post procedural complication, at 3.7%. It does not provide enough detail in that listing to attribute the term to a particular group or to infer further event circumstances. Deaths are not reported in the registry record; the death fields are blank rather than reporting a count.

Serious adverse event counts describe events recorded during the study and do not, on their own, establish whether an event was caused by treatment. The registry does not provide detailed event narratives, timing, relatedness assessments, or a comprehensive safety analysis. The study’s treatment period was 12 weeks, so the listed figures also do not describe longer-term safety. The counts should be interpreted as a limited registry summary, not as a complete comparative safety assessment.

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

The primary finding is an estimated difference of 0.01 mm in end-of-treatment AWT-Pi10 between AZD9668 and placebo, with a confidence interval from -0.043 to 0.063 and an unadjusted p-value of 0.711. The interval includes zero, and the test does not provide clear statistical evidence of a between-group difference on this endpoint. The result is uncertain within the range represented by the interval.

This does not demonstrate that AZD9668 and placebo are equivalent. Equivalence requires a suitable design and a prespecified margin defining how much difference would be considered acceptably small. Such a design and margin are not reported in the registry record. Nor does the result establish that no difference is possible; the interval is compatible with values on both sides of zero.

The result is specific to an imaging measure of airway structure, the analysis population described for that outcome, and the assessment after 12 weeks. It does not establish effects on symptoms, exacerbations, daily functioning, long-term disease progression, or other outcomes. Those questions cannot be answered from AWT-Pi10 alone. The registry does not report a threshold connecting a change in this measure to a clinically meaningful difference.

The trial’s randomized, placebo-controlled design is relevant to interpreting the group contrast, but important details of the analysis and missing-data handling are not reported. The primary analysis includes outcome-specific participant counts smaller than the enrollment figure, and the registry’s analysis-population description is incomplete. These limitations should temper confidence in any broader conclusion.

In general, statistical significance, clinical importance, and certainty are separate ideas. The p-value addresses compatibility with a statistical null under the test assumptions; the estimate describes the observed contrast; and the confidence interval conveys uncertainty around it. Here, none of these alone answers whether the imaging difference matters clinically. That judgment needs context and evidence not reported in the registry record.

17. Why This Trial Matters Statistically

This trial is statistically useful as an example of why an estimate and its uncertainty deserve attention alongside a significance test. The primary group means are close, the estimated difference is 0.01 mm, and the interval extends from -0.043 to 0.063. The unadjusted p-value of 0.711 does not provide clear evidence of a difference, but it should not be turned into a claim of equivalence or proof of no effect.

The distinction between standard errors and standard deviations is also important. The registry reports standard errors for the least-squares means, while the planning illustrations require an estimate of participant-level variation. Those illustrations use an approximate pooled standard deviation derived from the posted summary statistics. They therefore depend on assumptions and are not the same as the original sample-size justification, which is not reported in the registry record.

The study also highlights how outcome-specific analysis populations affect interpretation. The primary endpoint has fewer analysed participants than the listed enrollment, and different secondary outcomes have different analysis counts. Without further information on missing outcomes and analysis procedures, readers cannot fully assess the source or implications of those differences.

Finally, the registry lists numerous secondary measures but does not report a multiplicity strategy or analyses for all listed outcomes. That makes clear separation of primary and secondary evidence important. The primary endpoint addresses a defined structural-imaging question; secondary measurements may add context, but unadjusted results across many outcomes are less confirmatory. These are general lessons in reading clinical trial results, not claims that any particular unreported procedure was or was not used.

18. Limitations

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

The registry record leaves important aspects of the trial design and analysis unspecified. It does not report the original sample-size justification or the statistical assumptions used to plan enrollment. The planning illustrations based on the observed effect cannot fill that gap. The detailed statistical analysis plan, including model specification and any adjustment strategy, is also not reported in the registry record.

The primary analysis is based on an outcome-specific efficacy set, with 17 participants in the AZD9668 group and 19 in the placebo group. The registry’s description of the analysis population is incomplete, and the reasons for the difference between enrollment and endpoint analysis counts are not reported. Missingness, withdrawals, adherence, and the handling of unavailable measurements are not described in sufficient detail to assess potential bias.

The registry provides least-squares means and standard errors but does not identify the model covariates or explain how the estimates were obtained. It does not specify the confidence level or construction method for the posted interval. The comparison should therefore be read from the reported summary, without assuming an undocumented adjustment or inferential procedure.

The primary endpoint is an imaging measure at day 84. The registry does not report a threshold for clinically meaningful change, and the endpoint alone does not answer questions about symptoms or longer-term outcomes. The limited treatment period also constrains interpretation of the safety summary. The registry reports a small number of serious events but does not provide detailed descriptions or relatedness assessments.

Although multiple secondary outcomes are listed, numerical results are not posted for every listed outcome, and no multiplicity plan is reported. These gaps restrict assessment of the full pattern of evidence and the possibility of selective reporting. They are limits of what can be concluded from the registry record, rather than evidence that particular analyses or procedures were absent.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effect on Structural Changes in Airways, Measured by MSCT, of Twice Daily 60mg AZD9668 for 12 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients — NCT01054170.
• Registry record last updated 2012-08-20; status last verified 2012-08.
• Results first posted 2012-07-25.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT01054170 is a completed, randomized, double-blind, placebo-controlled, parallel-group, multicentre Phase II study of AZD9668 in adults with COPD. The registry lists quadruple masking and enrollment of 52. Treatment was oral AZD9668 at 60mg twice daily or placebo for 12 weeks.

The primary endpoint was AWT-Pi10, measured by MSCT at day 84. The reported least-squares means were 3.84 mm for AZD9668 and 3.83 mm for placebo; the mean difference was 0.01 mm, with a confidence interval from -0.043 to 0.063 and an unadjusted p-value of 0.711. The result does not provide clear statistical evidence of a group difference, and it does not establish equivalence.

The registry lists secondary imaging and lung-function outcomes and a limited safety summary. Important details about the original sample-size plan, analysis methods, multiplicity, and missing data are not reported in the registry record. Interpretation is therefore confined to the posted outcome estimates and their stated limitations.