A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Bronchiectasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Bronchiectasis (NCT00769119), a randomized phase 2 study. The primary outcome is Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline.

2. Clinical Question

3. Trial Design

This was a Phase II randomized, placebo-controlled, parallel-group study of oral AZD9668 in patients with bronchiectasis. The stated treatment period was 28 days. The registry reports enrollment of 38 participants and lists the study as completed. The recorded start is 2008-09, and the primary completion is 2009-04.

Random allocation and a parallel-group model are recorded. The masking field identifies the study as quadruple-masked, while the official title calls it double-blind. Those descriptions are both present in the registry record; further detail about who was masked, how masking was maintained, or whether it was assessed is not reported in the registry record. The arm descriptions contain no additional details.

The two groups are identified as AZD9668 and placebo. The posted primary-endpoint estimates use 18 participants in the AZD9668 arm and 10 in the placebo arm. These analysis counts are smaller than the overall enrollment, and the registry describes an efficacy analysis set requiring treatment exposure and outcome measurements. Reasons that individual participants did not contribute to the posted endpoint estimates are not reported in the registry record.

The study's purpose was to investigate the effect of 28 days of AZD9668 and compare it with placebo. The primary endpoint was a ratio of absolute neutrophil count at end of treatment to baseline, using averages across three visits in each period. Secondary outcomes include ratios for inflammatory markers and urine desmosine. The registry record does not report a sample-size justification, detailed randomization procedures, planned interim analyses, or a complete statistical analysis plan. No specific dose or adherence information is 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.

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 Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline, measured over End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits..

The primary endpoint is the ratio of absolute neutrophil count at the end of treatment to baseline. It is defined as the mean from three end-of-treatment visits, taken during day 21 to 28, divided by the mean from three baseline visits. The endpoint therefore summarizes a change in the level of a continuous biological measure across the treatment period, expressed as a ratio rather than as a raw difference.

A ratio can be interpreted relative to 1: a value of 1 represents equal values in the numerator and denominator, while values on either side indicate that the end-of-treatment mean is respectively higher or lower than the baseline mean. This is a general explanation of ratio measures. The AZD9668 arm's posted least-squares mean is 1.08, with a 95% confidence interval from 0.6 to 1.72. The placebo arm's estimate is 1.01, with a 95% confidence interval from 0.73 to 1.6.

Using several visits in each period can make the endpoint reflect an average across measurements rather than a single visit. That is a general feature of averaging repeated measurements; the registry does not report the rationale for selecting these particular visits or explain how within-person measurements were handled in the model. Absolute neutrophil count is the measure named by the registry as the primary outcome. The record does not establish that this biomarker is a substitute for symptoms, daily functioning, or other clinical outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the reported estimate represent?

The primary outcome is continuous and is reported as a least-squares mean of a ratio. A continuous outcome can take values across a scale rather than belonging to a small set of categories. A least-squares mean is generally a model-based mean, which may account for terms included in the analysis model. The registry record does not identify the model, its covariates, or the exact estimation procedure, so the reported values should not be attributed to a particular adjustment strategy.

The ratio compares the average absolute neutrophil count across three visits at the end of treatment with the average across three baseline visits. In general, a ratio of 1 represents equality between the quantities being compared. A ratio above 1 indicates a larger numerator than denominator, and a ratio below 1 indicates a smaller numerator. These are general properties of a ratio, not claims about the clinical meaning of a particular value.

How should the confidence intervals be read?

The registry reports a 95% confidence interval for each arm's estimate. In general, a confidence interval communicates how precisely an estimate has been determined under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval on the same scale, while a wide interval signals substantial uncertainty about the estimate. It is not an interval containing most individual measurements, and it does not account for every possible source of uncertainty, such as model misspecification or missing data.

The AZD9668 estimate is 1.08, with a 95% confidence interval from 0.6 to 1.72. The placebo estimate is 1.01, with a 95% confidence interval from 0.73 to 1.6. Each interval includes values below and above 1. The registry does not report a confidence interval for a treatment-versus-placebo contrast. In general, separate arm-level intervals do not directly quantify the uncertainty in a difference between arms; that contrast needs its own estimate and interval.

Why is a between-group analysis important?

For a randomized comparison, the central treatment question concerns how outcomes differ between assigned groups. An arm-level result describes the outcome estimate within one group, but a baseline-to-end ratio within that group does not isolate the effect of treatment from changes that may also occur under placebo or over time. The placebo group provides a comparator, but a quantitative comparison still requires a reported contrast or a suitable model-based test. No such inferential comparison is reported for the primary endpoint in the registry record.

Randomization is intended, in general, to support a fair comparison by allocating participants independently of their expected outcomes. The registry identifies allocation as randomized but does not report the sequence-generation method, allocation concealment, or other operational details. The effect of any departures from the intended design cannot be evaluated from the posted information alone.

What does the analysis population imply?

The efficacy analysis set includes patients who received at least one dose and had a baseline and at least one post-randomisation measurement for the outcome. This is an outcome-specific eligibility rule. The record says patients were analysed by randomized treatment, although the description ends mid-sentence. It does not provide a complete definition of the analysis population or clarify how participants with incomplete measurements were handled.

In general, restricting an analysis to participants with observed measurements can reduce the amount of data available and may affect interpretation if data availability is related to outcome or treatment. The posted primary-endpoint counts are 18 for AZD9668 and 10 for placebo, compared with enrollment of 38 overall. The reasons for the analysis counts and any imputation or sensitivity analyses are not reported in the registry record.

What is over-dispersion, and is it relevant?

Over-dispersion is a general concern for some statistical models when observed variability is greater than the model assumes. It often matters for count or binary outcomes and can make standard errors too small if ignored. The primary endpoint in this study is continuous and summarized as a ratio, so the registry's posted information does not indicate that an over-dispersion adjustment was used or was needed. Details of the variance model are not reported in the registry record; no more specific claim about its treatment is possible.

How should planning illustrations be understood?

Any sample-size figures associated with the posted results are planning illustrations based on the observed effect, not the trial's original design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. In general, such calculations ask how many participants per arm might be needed under those assumptions to detect a specified effect. They do not describe the number actually analyzed, demonstrate the study's observed power, or establish that the original trial had those design assumptions. The registry record does not report the original sample-size justification.

The validity of any planning illustration depends on its assumptions, including the effect used as a reference and the analysis model. Because the observed effect can be uncertain, a planning calculation built from it is not independent evidence that the effect is real or reproducible. Those illustrations should be understood as hypothetical design scenarios, not as an additional result of the randomized comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists secondary outcomes involving TNF α, IL-6, IL-1β, RANTES, MCP-1, IL-8, LTB4, and urine desmosine, alongside the primary absolute neutrophil count endpoint. Testing or interpreting many outcomes can increase the chance of finding an apparently notable result by chance. In general, a multiplicity plan specifies how that risk is addressed, for example by defining a primary outcome hierarchy or adjusting inference across tests. Such a plan is not reported in the registry record. The registry also does not provide a complete account of which secondary outcomes were analyzed or how their results should be interpreted relative to the primary endpoint.

The efficacy analysis set required at least one dose and both a baseline and at least one post-randomisation measurement for each outcome. This rule means that the analyzed population may vary by outcome. The primary endpoint counts are 18 for AZD9668 and 10 for placebo, whereas total enrollment was 38. The registry record does not explain the difference between enrollment and these analysis counts, or report reasons for missing measurements, withdrawals, or exclusions.

Missing outcomes can affect interpretation in general, particularly if the probability that a measurement is missing depends on treatment or the unobserved outcome. The registry does not report an imputation method, a missing-data sensitivity analysis, or a detailed accounting of participants by analysis population. The record says participants were analyzed by randomized treatment, but its description is incomplete. It is therefore not possible to assess fully whether the analysis preserved the intended randomized comparison or how robust the findings are to missing data.

The registry does not report interim analyses, stopping rules, a detailed statistical analysis plan, or a sample-size justification. Their absence from the record should not be taken to establish that they were or were not conducted; these details are not reported in the registry record.

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

For serious adverse events, the registry reports zero affected participants among 22 at risk in the AZD9668 group and zero among 16 at risk in the placebo group. These are the posted serious-event counts. The record does not list serious-event terms. Death counts are not reported in the registry record.

The registry separately reports other adverse events for 13 of 22 participants at risk in the AZD9668 group and 15 of 16 at risk in the placebo group. These figures are counts of participants with other adverse events, not counts of individual events, and they do not identify event type, severity, timing, or attribution. No interpretation about causation should be made from these counts alone.

In general, safety counts describe what was recorded over the study's observation period, and zero reported serious events does not establish that an event is impossible or that risks are absent. The registry record does not give detailed exposure duration by participant, event listings, or an analysis comparing safety between groups. The groups also have different numbers at risk in the posted safety data. These limitations mean the figures are descriptive rather than a complete assessment of comparative safety.

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

The registry record documents a randomized Phase II study of 28-day oral AZD9668 versus placebo in patients with bronchiectasis. For the primary endpoint, it reports an AZD9668 least-squares mean ratio of 1.08, with a 95% confidence interval from 0.6 to 1.72, and a placebo estimate of 1.01, with a 95% confidence interval from 0.73 to 1.6. These are arm-level summaries of the end-of-treatment to baseline absolute neutrophil count ratio.

The results do not provide a formal estimate of the treatment-versus-placebo difference, a confidence interval for that comparison, or a test of the primary treatment contrast. The two arm-level estimates and their separate intervals are not enough to determine the size or precision of a between-group effect. The registry record also does not report a clinical interpretation threshold for this biomarker endpoint. Consequently, these posted results cannot establish whether the groups differ in a clinically meaningful way.

The endpoint is a biomarker measured over a limited treatment period. In general, a biomarker result does not by itself establish a change in symptoms, daily function, disease course, or other patient-centered outcomes. The record does not provide results for such outcomes in the registry record for this analysis. The findings should not be read as evidence that AZD9668 does or does not treat bronchiectasis.

The analysis counts are 18 in the AZD9668 arm and 10 in the placebo arm, against overall enrollment of 38. Without a detailed account of missing data and analysis populations, the extent to which the posted estimates represent all randomized participants is uncertain. Safety counts are also descriptive: zero serious adverse events are recorded in either group, while other adverse events are recorded for participants in both groups. The record lacks the detail needed to make a comprehensive comparative safety assessment.

The appropriate conclusion is limited: the registry posts uncertain arm-level estimates for the primary ratio endpoint and descriptive adverse-event counts. It does not report the inferential comparison needed to answer the principal treatment-versus-placebo question.

13. Why This Trial Matters Statistically

This trial illustrates a central distinction in randomized-trial reporting: an estimate within each arm is not the same as an estimate of the treatment contrast. The primary results give a ratio estimate and confidence interval for AZD9668 and for placebo. Those summaries describe each group separately. The main comparative question requires a direct contrast between groups and an uncertainty measure for that contrast, neither of which is reported in the registry record.

The distinction matters because a value within one group can reflect several influences, including the treatment, time, and changes that may also occur in the comparator group. A placebo-controlled design creates the basis for a comparison, but the design alone does not supply the numerical result of that comparison. Readers need to distinguish the trial's randomized structure from the particular results posted for the endpoint.

The record also shows why analysis populations and missing measurements matter. Enrollment is 38, while the primary-endpoint estimates use 18 participants in the AZD9668 group and 10 in the placebo group. The registry describes eligibility for the efficacy analysis but does not explain the gap between enrollment and endpoint counts. Without that accounting, readers cannot fully assess the representativeness of the analyzed participants or the influence of missing data.

Finally, the trial offers a useful example of the limits of interpreting a biomarker endpoint. The primary measure is a ratio of absolute neutrophil count across specified visits, with arm-level confidence intervals. That is informative about the measured endpoint, but it does not automatically translate into evidence about patient experience or clinical benefit. Careful interpretation separates what the statistic measures from the broader clinical question it may be intended to inform.

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 registry record provides limited detail about the trial's statistical methods. It reports least-squares means and 95% confidence intervals for the primary outcome, but does not identify the fitted model, covariates, handling of repeated visits, or method used to calculate uncertainty. It also does not report a direct contrast between randomized groups, a p-value, or an adjusted treatment effect. This makes the primary results descriptive rather than a complete inferential comparison.

The primary endpoint uses three baseline visits and three end-of-treatment visits, with end-of-treatment measurements taken during day 21 to 28. The record does not explain the rationale for those windows, report visit-level data, or describe how participants with fewer measurements were handled. Although the efficacy set requires a baseline and at least one post-randomisation measurement, the endpoint definition refers to means across three visits. The treatment of incomplete visit series is not reported in the registry record.

The analysis counts of 18 and 10 are below the overall enrollment of 38. Reasons for non-inclusion, withdrawals, exclusions, and missing outcomes are not reported in the registry record. The record does not provide sensitivity analyses to assess the potential impact of missing data. The stated efficacy analysis set is therefore not enough to determine how representative the endpoint estimates are of all randomized participants.

Further limitations are the absence of a reported sample-size justification, detailed allocation procedures, interim-analysis information, and a complete statistical analysis plan. The registry's title describes the study as double-blind, whereas its masking field says quadruple; details resolving that difference are not reported. The primary measure is a biomarker ratio, and the registry entries do not include a clinical interpretation threshold or results for patient-centered outcomes. These omissions constrain both statistical and clinical interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Bronchiectasis — NCT00769119.
• 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.

18. Record Summary

NCT00769119 is a completed randomized Phase II, placebo-controlled, parallel-group study of 28-day oral AZD9668 in patients with bronchiectasis. Enrollment was 38. The registry records the study start as 2008-09 and primary completion as 2009-04. Its masking field says quadruple, while the official title describes the study as double-blind.

The primary endpoint was the ratio of absolute neutrophil count at the end of treatment to baseline, based on three visits in each period. The AZD9668 arm estimate was 1.08, with a 95% confidence interval from 0.6 to 1.72, among 18 participants; the placebo estimate was 1.01, with a 95% confidence interval from 0.73 to 1.6, among 10 participants. No formal between-arm analysis is reported.

The safety record reports zero serious adverse events among 22 at risk with AZD9668 and zero among 16 at risk with placebo. Other adverse events affected 13 of 22 and 15 of 16 participants, respectively. Death counts are not reported in the registry record.