Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis (NCT01313624), a randomized phase 3 study. The primary outcome is Change in QOL-B Respiratory Symptoms Score at Day 28.

2. Clinical Question

The clinical question concerns whether the change in respiratory symptoms over the first blinded treatment course differed between participants assigned to repeated courses of inhaled aztreonam (AZLI) and those assigned to placebo. The measure was the Respiratory Symptoms score from the Quality of Life Questionnaire-Bronchiectasis (QOL-B), recorded at baseline and Day 28. The registry describes participants with non-cystic fibrosis bronchiectasis and gram-negative endobronchial infection.

The Day 28 comparison is the primary endpoint. The scale runs from 0-100, with higher scores representing better quality of life. A change from baseline describes how the score shifted over the first 28-day course; a between-group contrast asks whether the average shift differed between the randomized groups. The registry also lists respiratory-symptom change at Day 84 and time to protocol-defined exacerbation as secondary outcomes, but numerical results for the latter are not reported in the registry record.

The question is about the average score change in the analyzed participants, not whether every participant experienced the same change. The posted results include both group averages and a sponsor analysis that adjusts for repeated measurements using MMRM. The estimates are imprecise enough that the registry results do not establish a clear between-group difference. They also do not, by themselves, resolve whether any estimated score difference would be important to participants; a threshold for a meaningful change is not reported in the registry record.

3. Trial Design

NCT01313624 is a completed Phase 3 randomized, double-blind, parallel-group, placebo-controlled trial sponsored by Gilead Sciences. The registry records enrollment of 266 participants. It lists bronchiectasis as the condition and describes the study population more specifically as people with non-CF bronchiectasis and gram-negative endobronchial infection. The study began in 2011-04, and primary completion was in 2013-03.

Participants were randomized to one of two blinded sequences. The AZLI-AZLI group received two 28-day courses of blinded AZLI, with 28 days off treatment after each course. The Placebo-AZLI group received matching placebo during those two blinded courses on the same schedule. Following the blinded phase, both groups received a 28-day open-label AZLI course and then had 56 days of treatment-free follow-up. The primary endpoint was measured at the end of the first blinded course, from baseline to Day 28.

Randomization is intended to make the groups comparable at the outset, on average, so that differences in outcomes can be interpreted in relation to assigned treatment rather than deliberate allocation. Double masking is intended to reduce the influence of treatment knowledge on participants’ reports and on study conduct. The parallel-group structure means participants remained in their assigned treatment sequence rather than crossing between blinded treatments during the primary comparison.

The registry reports outcome-specific analysis counts of 117 in the AZLI-AZLI group and 124 in the Placebo-AZLI group for the primary outcome. These counts refer to participants with scores at both baseline and Day 28 in the ITT Analysis Set, as described in the endpoint population. The reason these counts differ from overall enrollment is not reported in the registry record. Details of the randomization procedure, allocation concealment, and the trial’s original sample-size justification 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: 348 participants were screened and 266 were randomized and treated, and comprise the Safety Analysis Set and the Intent-to-Treat (ITT) Analysis Set.

Double-Blind Phase

Reasons for not completing this period:

Open-Label Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants in the ITT Analysis Set with scores at both baseline and Day 28 were analyzed.

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.

Population: ITT Analysis Set

6. Primary Endpoint

The registry lists the primary outcome as Change in QOL-B Respiratory Symptoms Score at Day 28, measured over Baseline to Day 28.

The primary endpoint is the mean change in the QOL-B Respiratory Symptoms score from baseline to Day 28, corresponding to the end of Course 1. QOL-B is a questionnaire for bronchiectasis-related quality of life. The respiratory-symptom score is transformed onto a 0-100 scale, and higher scores represent better quality of life. The endpoint therefore summarizes the average direction and size of score change over the first blinded course.

Using change from baseline focuses the comparison on how scores shifted during the treatment period rather than on Day 28 scores alone. Comparing the average change between randomized groups addresses whether the pattern of change differed by assigned blinded treatment. A group mean is useful for describing the average response, while the standard deviation shows how widely individual changes varied around that average. The observed standard deviations are substantial relative to the average changes, so participants’ score changes were not all alike.

The registry says that participants in the ITT Analysis Set with scores at both baseline and Day 28 were analyzed. This makes the endpoint result dependent on having both measurements available for the stated analysis. The registry does not report the amount or handling of missing primary endpoint data, the threshold used to define a clinically important score change, or whether the analysis population included all randomized participants under a particular missing-data strategy.

7. Results Posted in the Registry

• AZLI-AZLI: mean 7.40 versus 5.70 on control; difference 1.70 (95% CI -2.85 to 6.25), standardized effect d = 0.10; z-test p = 0.464.

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.

Change in QOL-B Respiratory Symptoms Score at Day 84

• 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:
  • AZLI-AZLI: mean 7.40 versus 4.70 on control; difference 2.70 (95% CI -2.41 to 7.81), standardized effect d = 0.14; z-test p = 0.300.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AZLI-AZLI and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary endpoint results follow a broadly similar pattern to the primary comparison: the estimated between-group differences are modest relative to their uncertainty, and the reported confidence intervals include zero. This overall pattern does not provide a clearly separated secondary signal that would overturn or independently sharpen the primary interpretation. It is best viewed as contextual evidence rather than as a separate confirmation.

One secondary outcome is respiratory-symptom score change at Day 84, after the first blinded course and the subsequent study schedule. Because the blinded sequences continued before both groups received open-label AZLI, later measurements reflect a different point in the protocol from the Day 28 primary endpoint. The treatment context and available analysis participants therefore matter when comparing later and earlier results. The other listed secondary outcome is time to protocol-defined exacerbation; its numerical results are not reported in the registry record.

Secondary endpoints are often interpreted with less weight when many outcomes or time points are examined. In general, testing multiple hypotheses increases the chance that at least one apparently notable result will arise by chance if no corresponding effects exist. The registry does not report a multiplicity adjustment or a prespecified hierarchy for interpreting secondary outcomes. Consequently, unadjusted secondary p-values, where reported, should not be treated as if they were the sole primary test.

The endpoint summaries are useful for seeing whether the broad direction of findings is consistent across time, but they do not establish that the endpoints measure the same thing or answer interchangeable questions. A symptom score and time to an exacerbation have different meanings and may have different distributions and analysis requirements. The record does not report enough detail to assess the analysis plan for the time-to-event endpoint or how its result would be integrated with the primary finding.

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

• Change in QOL-B Respiratory Symptoms Score at Day 84
• Time to Protocol-Defined Exacerbation (PDE)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: each participant has a score change, and the registry reports group means and standard deviations. A mean describes the central average of the observed values. A standard deviation describes the spread of individual values around that mean; it is not the uncertainty in the estimated group mean. The posted group standard deviations, 21.37 and 13.62, indicate appreciable variation among participants’ score changes.

What does the unadjusted mean difference represent?

The recalculated mean difference is the AZLI-AZLI mean minus the Placebo-AZLI mean, using the posted means. The estimate is 1.7 units. This is a simple contrast of group averages and does not account for any covariates or repeated-measures structure. Its confidence interval and p-value are recalculated from posted summary statistics; they are not the sponsor’s model output. The recalculated pooled standard deviation is 17.81, and the standardized effect estimate is 0.096. These standardized quantities describe the contrast relative to variability, but they do not supply a clinical-importance threshold.

Why does the sponsor use MMRM?

The reported analysis uses MMRM, a mixed model for repeated measures. In general, this class of model can represent correlations among repeated observations from the same participant and can compare groups while using repeated outcome information under the model’s assumptions. The registry names MMRM and reports a difference in least squares means, but the specific model terms, covariance structure, handling of missing observations, and any covariates are not reported in the registry record. A least squares mean is a model-based group mean or contrast, not necessarily the raw arithmetic average of the participants’ observed changes.

Because the sponsor’s analysis is model-based and the recalculation uses only summary means, standard deviations, and group sizes, the estimates need not match exactly. The recalculation is useful for an independent, unadjusted description, but it does not reproduce the sponsor’s full analysis. The registry marks discrepancy as false, so there is no flagged disagreement requiring the sponsor’s estimate to take precedence on that basis.

How should confidence intervals and p-values be understood?

A confidence interval expresses uncertainty around an estimated effect under the analysis method. A 95% confidence procedure, in general, would cover the true parameter in 95% of repeated studies under its assumptions. For an individual study, the interval gives a range of values compatible with the data and method; it is not a statement that there is a 95% probability the fixed true effect falls inside that particular interval. An interval crossing zero means that the data and method do not distinguish the estimated direction from no difference at that confidence level. It does not prove there is no effect.

A p-value is conditional on a specified statistical model and null hypothesis. It measures how surprising the data, or more extreme data, would be if the null were true and the assumptions held. It is not an effect-size measure and does not describe clinical importance. The sponsor reports p = 0.68 for the primary MMRM comparison; the simple recalculation reports p = 0.464. The distinction between model-based and unadjusted analyses matters when interpreting the different values.

Why is variation important?

When individual outcomes vary widely, a group mean can be estimated less precisely unless there is substantial information. General statistical reasoning explains why: random variation obscures the group contrast. Over-dispersion, in general, means variability is greater than a model would expect under a simpler variance assumption. If present and ignored, it can make uncertainty appear too small. The registry does not report an over-dispersion assessment for this continuous outcome, and the concept should not be mistaken for a finding about this trial.

For planning, the posted illustrations use the observed effect and assume a two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. They show hypothetical participant counts for detecting specified fractions of the observed effect. These are planning illustrations, not the trial’s original design calculations. The original sample-size justification, its anticipated effect, and any original power target are not reported in the registry record.

The trial also includes a time-to-event secondary outcome, but no numerical analysis for it is posted in the registry record. General time-to-event methods account for the timing of events and may also accommodate censoring, when follow-up ends before an event is observed. The registry’s sample-size assumptions say time-to-event illustrations would report total events, whereas the illustrations for other outcomes report participants per arm. No event-based figures are available in the listed secondary results.

11. Confidence Intervals and Precision

The primary sponsor estimate is a difference in least squares means of 0.8, with a 95% confidence interval from -3.1 to 4.7. This interval includes zero and covers effects in either direction. Its width indicates that the estimate is not highly precise: the observed data are compatible with more than one plausible magnitude and direction of the between-group contrast under the sponsor’s model. The interval should be interpreted alongside the estimated difference, not as a separate result.

The unadjusted recalculation gives a mean difference of 1.7, with a 95% confidence interval from -2.854 to 6.254. This interval likewise crosses zero and spans both negative and positive values. The sponsor and recalculated intervals arise from different methods, so they should not be treated as interchangeable. The sponsor’s MMRM interval is the result of the reported trial analysis; the recalculated interval is based on the posted summary statistics.

In general, precision concerns how narrowly an analysis estimates the effect, while statistical significance concerns whether an interval excludes the null value under a chosen procedure. A wide interval can include no difference while still allowing effects that could be meaningful in either direction. The registry does not report a threshold for a clinically meaningful QOL-B change, so the practical importance of values within either interval cannot be classified from the record alone.

The primary outcome analysis includes 117 AZLI-AZLI participants and 124 Placebo-AZLI participants with the required scores. The extent to which missing scores or other exclusions affect precision is not reported in the registry record. The observed standard deviations also show that individual score changes varied substantially, a feature that contributes to uncertainty in group comparisons.

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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculations. For this continuous outcome, the figures are participants per arm, rather than total events. The assumptions are a two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set as a stated fraction of the observed effect.

The 80% power column describes the hypothetical number of participants per arm needed for an analysis to have an 80% chance of detecting the specified effect under the planning assumptions, if that effect and the assumptions were correct. The 90% power column uses a higher target chance of detection and therefore requires more participants for the same assumed effect. These values are planning quantities, not counts observed in the trial.

The listed rows consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. As the assumed effect becomes smaller, more participants are needed to distinguish it from random variation at the same significance level and target power. The estimates are illustrations rather than a recommendation for a future trial; the appropriate target effect and design assumptions would need justification. The trial’s own original sample-size justification and assumptions are not reported in the registry record.

The curve should be read as the relationship between assumed effect and required sample size under the same general planning framework, rather than as observed trial performance. Neither the curve nor the listed participant counts tells how much power this completed trial had after the results were known. This is not observed power.

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 = 1.700; pooled standard deviation σ = 17.808.
2. n = 2 × (1.96 + 0.842)² × 17.808² / 1.700² = 1,722.5, rounded up to 1,723 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 <- 1.7                      # observed difference in means
sigma <- 17.8078495221211                     # 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(1313624)
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 = 1,723 (80% power), 2,306 (90% power)
 75% of observed effect: n per arm = 3,063 (80% power), 4,100 (90% power)
 50% of observed effect: n per arm = 6,891 (80% power), 9,224 (90% power)
power.t.test: 1723.5 
Simulated power at n = 1,723 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. Analyses Reported by the Sponsor

The sponsor reports an MMRM analysis for the primary endpoint, with a difference in least squares means of 0.8, a 95% confidence interval from -3.1 to 4.7, and p = 0.68. This is the registry’s reported inferential analysis. MMRM is a model-based method, and the least squares mean contrast may differ from a direct subtraction of the observed group averages.

The unadjusted recalculation from the posted summary statistics estimates a mean difference of 1.7, with a 95% confidence interval from -2.854 to 6.254 and p = 0.464. It is not an attempt to reproduce the sponsor’s model. It uses the group means, standard deviations, and analysis counts, without the repeated-measures model structure or any model terms that may have been used by the sponsor.

The two estimates differ in magnitude, but both intervals include zero and both comparisons are uncertain. The registry does not flag a discrepancy. The sponsor’s analysis therefore remains the trial’s reported model-based result, while the recalculation offers a separate, unadjusted check based on summary data. Details of the sponsor model beyond the method name and reported output are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary endpoint at Day 28 and lists secondary outcomes including respiratory-symptom change at Day 84 and time to protocol-defined exacerbation. It records three outcome measures and two analyses. However, a complete statistical analysis plan describing the hierarchy among outcomes, the planned contrasts, and the handling of multiple testing is not reported in the registry record.

Multiplicity matters because examining several endpoints, time points, or analyses creates multiple opportunities for an apparently unusual result. In general, without adjustment or a prespecified testing sequence, the chance of at least one false-positive finding across a family of tests can be greater than the chance associated with an individual test. The registry does not report whether a multiplicity-control procedure was used. Secondary findings should therefore be interpreted as supportive or exploratory rather than as independent confirmatory evidence unless further analysis-plan details are available.

The primary endpoint population is described as participants in the ITT Analysis Set with scores at both baseline and Day 28. The record does not explain how missing scores were handled, whether all randomized participants were included in other analyses, or what assumptions were used for incomplete repeated measurements in the MMRM. The difference between overall enrollment and the endpoint analysis counts is apparent, but reasons for the unavailable endpoint scores are not reported in the registry record.

The phrase ITT Analysis Set does not by itself establish that every randomized participant contributed to this particular endpoint analysis. The stated requirement for scores at both time points means the primary summary includes participants with those measurements. In general, complete-case analyses can be affected if the availability of measurements is related to outcomes or treatment; appropriate missing-data methods rely on assumptions that should be described. The registry’s model name alone is insufficient to determine the missing-data assumptions or their plausibility.

Allocation concealment details, model covariates, covariance structure, sensitivity analyses, interim analyses, and the original sample-size justification are not reported in the registry record. Their absence limits independent assessment of the analysis choices, but it does not itself demonstrate that the choices were inappropriate.

16. 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: infective exacerbation of bronchiectasis (5.7%), pneumonia (4.9%), chronic obstructive pulmonary disease (2.2%), bronchospasm (2.2%), atrial fibrillation (1.6%).

The registry lists serious adverse event counts separately for the blinded and open-label periods. In the double-blind AZLI-AZLI group, 28 of 134 participants were recorded as affected by a serious adverse event; in the double-blind Placebo-AZLI group, 13 of 132 were affected. In the open-label period, the corresponding counts were 9 of 96 in the AZLI-AZLI sequence and 18 of 122 in the Placebo-AZLI sequence.

These are participant counts with serious adverse events, not counts of all individual events. The registry also lists serious-event terms and percentages, including infective exacerbation of bronchiectasis at 5.7% and pneumonia at 4.9%. The terms may describe events rather than mutually exclusive participant categories, so the percentages should not be added or interpreted as a single overall risk.

The open-label groups are observed in a different treatment period after the blinded courses, and both sequences received open-label AZLI. These figures are not a direct randomized comparison of AZLI against placebo. The registry does not report deaths for these groups. Adverse-event counts describe events recorded during the trial; they do not alone establish that a treatment caused an event or provide a complete benefit-risk assessment.

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

The primary result estimates the average change in a patient-reported respiratory-symptom score during the first blinded course and compares that change between randomized groups. The sponsor’s model-based estimate is close to zero relative to its uncertainty, and its confidence interval includes no difference. The unadjusted recalculation has the same broad interpretation: it does not establish a clear difference between group averages.

This is not proof that the treatments are equivalent, nor proof that there is no possible effect. The intervals include a range of values, and the registry does not report an equivalence margin or a threshold defining a clinically important score change. The estimates also describe group averages; individual participants’ changes varied, as reflected by the standard deviations.

The endpoint concerns QOL-B respiratory symptoms, not all aspects of bronchiectasis, infection status, exacerbation risk, or safety. The registry lists other outcomes, but the time-to-exacerbation numerical results are not reported in the registry record. Later open-label observations also answer a different question from the blinded Day 28 comparison because both randomized sequences eventually received AZLI.

The trial enrolled people described as having non-CF bronchiectasis and gram-negative airway infection. Results should not be generalized automatically to people outside this study population, to different treatment schedules, or to outcomes not measured. The record does not include enough detail to assess all aspects of generalizability, missing-data handling, model specification, or the clinical importance threshold.

Statistical uncertainty is not a reason to infer a particular individual outcome. These group-level results describe what was observed and how uncertain the estimated contrast is under the stated analyses. They do not replace an individualized clinical assessment or constitute treatment advice.

18. Why This Trial Matters Statistically

This trial illustrates several important statistical features of clinical research. A randomized, double-blind, placebo-controlled design can support a fair comparison of assigned treatments, while the interpretation still depends on what was measured, who contributed data, and how the analysis was conducted. The primary outcome is a patient-reported continuous score, so the result is an average change rather than a count of responders or a direct measure of a biological process.

The record makes a useful distinction between raw group summaries and the sponsor’s model-based analysis. Group means and standard deviations allow a transparent unadjusted comparison, while MMRM can account for repeated measurements under its assumptions. The analyses yield different point estimates and uncertainty intervals, underscoring why an independent recalculation should not be mistaken for a reproduction of the trial’s full model.

The confidence intervals emphasize that a nonsignificant result is not the same as evidence of no effect. They include zero, but also leave room for effects in either direction. Without a reported threshold for meaningful QOL-B change, statistical uncertainty cannot be translated directly into a judgment about practical importance.

The sample-size illustrations also show why planning depends on the effect a study aims to detect. Smaller assumed effects require more participants under the stated assumptions. These illustrations do not reveal the trial’s original rationale, which is not reported in the registry record, and they are not a retrospective measure of trial power.

Finally, the registry’s description of the endpoint population, secondary outcomes, and adverse events shows why interpretation requires attention to analysis populations, multiplicity, follow-up phase, and outcome type—not only a p-value.

19. 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.

Several trial-specific limitations affect how completely the results can be interpreted from the registry record. The primary endpoint analysis is described as including ITT Analysis Set participants with scores at baseline and Day 28, but the reasons some enrolled participants lack those paired scores are not reported. The amount and pattern of missing data, and the sensitivity of results to missing-data assumptions, are not reported in the registry record.

The sponsor identifies MMRM, but does not report the model terms, covariance structure, covariates, or detailed assumptions in the record. Those details would help readers assess how the least squares mean contrast was formed and how incomplete repeated observations were handled. The original statistical analysis plan, original sample-size justification, interim analyses, and multiplicity strategy are also not reported.

The QOL-B scale direction is clear, but a threshold for clinically meaningful change is not reported in the registry record. That makes it difficult to interpret whether the magnitudes compatible with the confidence intervals would be important to participants. In addition, the primary endpoint is measured at the end of the first course; it does not summarize every part of the repeated-course and open-label schedule.

The secondary time-to-exacerbation outcome is listed, but its numerical result is not reported in the registry record. The open-label phase does not offer the same blinded randomized comparison as the primary period because participants in both sequences receive AZLI. The serious adverse event counts are separated by study period, and the record does not report deaths for the listed groups. These limitations constrain conclusions about later outcomes and safety comparisons.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis — NCT01313624.
• Registry record last updated 2014-04-16; status last verified 2014-03.
• Results first posted 2014-04-16.
• 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.

23. Record Summary

NCT01313624 was a completed Phase 3 randomized, double-blind, parallel-group, placebo-controlled trial sponsored by Gilead Sciences, with enrollment of 266. It studied repeated AZLI courses in adults with non-CF bronchiectasis and gram-negative airway infection. The primary endpoint was change in QOL-B Respiratory Symptoms score from baseline to Day 28.

The sponsor’s MMRM estimate was a difference in least squares means of 0.8, with a 95% confidence interval from -3.1 to 4.7 and p = 0.68. The unadjusted recalculation was a mean difference of 1.7, with a 95% confidence interval from -2.854 to 6.254. Both intervals include zero. The registry does not report a clinically meaningful change threshold, detailed missing-data methods, or the original sample-size justification. Numerical results for time to protocol-defined exacerbation are not reported in the registry record.