A Safety, Tolerability and Efficacy Study in Chronic Obstructive Pulmonary Disease (COPD) Patients With QBM076.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety, Tolerability and Efficacy Study in Chronic Obstructive Pulmonary Disease (COPD) Patients With QBM076. (NCT01972776), a randomized phase 2 study. The primary outcome is Percentage of Participants With Adverse Events (Part 1).

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, triple-masked, parallel-group study with two parts. The registry record gives total enrollment as 48 and status as terminated. The study began in 2013-11, and primary completion was recorded as 2015-05. The reason for termination is not reported in the registry record.

Part 1 was described as a safety and tolerability study in participants with GOLD I-III COPD. Three QBM076 dose cohorts received 25 mg, 75 mg, or 150 mg twice daily for 14 days. Each cohort had a matching placebo group. The posted primary outcome is the percentage of participants with adverse events over 14 days, for all randomized Part 1 participants. The record reports 6.0 participants in each of the lower-dose QBM076 cohorts, 8.0 in the 150 mg cohort, and 7.0 in the placebo group.

Part 2 was described as an efficacy study in the same stated COPD severity range. Participants received QBM076 150 mg twice daily or matching placebo for 8 weeks. The registry record includes Part 2 safety data, but the primary outcome named in the record is specifically a Part 1 measure. The allocation process within the dose cohorts, treatment adherence, and any changes to the planned design are not reported in the registry record.

Several Part 1 secondary measures concern QBM076 exposure and pharmacodynamic activity, including plasma concentration measures, CD11b, and CXCR2 receptor occupancy. The registry record reports 22 outcome measures and 17 posted secondary outcomes. It gives no registered analysis entries.

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.

Part 1

Reasons for not completing this period:

Part 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized part 1 participants

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Adverse Events (Part 1), measured over 14 days.

The primary endpoint is the percentage of participants with adverse events in Part 1 over 14 days. It summarizes how often at least one adverse event was recorded in each treatment cohort during the stated period. The registry description says adverse events were counted and corresponding percentages tabulated; it does not give a more detailed operational definition, such as how recurrent events were handled for this endpoint.

Adverse-event incidence is used in safety and tolerability assessment because it provides a participant-level summary of whether an event occurred during treatment. Reporting a percentage allows readers to see the proportion affected within each cohort, while the cohort sizes provide context for how much information supports each percentage. With small groups, an individual participant can have a substantial influence on the reported percentage, and the estimate may be imprecise.

The posted Part 1 percentages are 33.0% for QBM076 Part 1 Cohort 1, 50.0% for QBM076 Part 1 Cohort 2, 63.0% for QBM076 Part 1 Cohort 3, and 71.0% for Placebo Part 1. These are descriptive results, not adjusted comparative estimates. No confidence intervals or hypothesis tests for the primary outcome are reported in the registry record. The endpoint describes observed adverse-event occurrence in these study groups; interpretation should account for the short 14-day period, small cohort sizes, and the absence of a reported inferential comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes this as a randomized, triple-masked, parallel-group Phase 2 study. In general, random allocation is intended to reduce systematic differences between treatment groups, while masking is intended to limit the influence of treatment knowledge on participant experience, clinical care, and outcome assessment. Those design features do not eliminate chance imbalances, particularly in small groups. The details of how randomization and masking were implemented are not reported in the registry record.

What does a percentage measure?

The primary outcome is a participant-level binary measure: a participant either had an adverse event recorded during the endpoint period or did not. The reported percentage expresses the share of participants in a cohort who had an event. It is a compact descriptive measure, but the percentage alone does not communicate its precision. Precision depends in part on the number of participants observed, and the Part 1 cohorts were small. The registry record does not post confidence intervals for these percentages.

How should a confidence interval be understood?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical procedure. A relatively wide interval indicates that the data are compatible with a broad range of values; a narrow interval indicates greater precision. No confidence intervals for the primary outcome are reported in the registry record, so the posted percentages should not be treated as though their uncertainty were quantified.

Why distinguish description from comparison?

A list of group percentages is descriptive. A comparative analysis would estimate a contrast between treatment groups and quantify uncertainty around that contrast, often with a confidence interval and a statistical test. The registry record reports no analysis entries and no inferential comparison for this endpoint. It is therefore not possible to use the listed percentages alone to determine whether any apparent difference is more than sampling variation. General statistical interpretation also requires attention to the analysis population, missing outcomes, and the prespecified method; those details are not reported in the registry record.

What do the safety counts add?

The safety listing separately reports serious adverse events and other adverse events. These are event categories, and a participant may have more than one event; counts of events should not automatically be interpreted as counts of distinct participants. The posted serious-event figures are counts by group, while the primary endpoint is a percentage of participants with adverse events. They answer related but different descriptive questions. Serious events are uncommon in the listed groups, so the observed counts are especially sensitive to individual cases. In general, sparse event data require cautious interpretation, and a formal comparison would need a suitable method and an estimate of uncertainty. Neither is reported in the registry record.

What are planning calculations?

In general, a sample-size calculation uses assumptions about the outcome rate or effect to estimate how many participants might be needed for a future study under a chosen statistical design. Such a calculation is a planning illustration, not a measure of the probability that the completed study detected a real effect. Any planning illustration based on the observed effect is particularly dependent on the observed estimate, which can be unstable in small groups. The registry record does not report the trial's own sample-size justification or planning assumptions. No planning calculation should be interpreted as observed power or as evidence that the study was adequately sized to answer a particular question.

The analysis methods for the primary endpoint, including any adjustment for covariates, handling of missing values, and treatment of multiple outcomes, are not reported in the registry record. The record identifies all randomized Part 1 participants as the primary population, but it does not describe a detailed analysis set or explain whether all randomized participants contributed an observed outcome. These omissions limit reproducibility and make it difficult to assess whether the posted summaries fully follow a prespecified plan.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("QBM076 Part 1 Cohort 1", "QBM076 Part 1 Cohort 2", "QBM076 Part 1 Cohort 3", "Placebo Part 1")
n      <- c(6, 6, 8, 7)
events <- c(2, 3, 5, 5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  QBM076 Part 1 Cohort 1  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  QBM076 Part 1 Cohort 2  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  QBM076 Part 1 Cohort 3  8  5  62.5  24.5  91.5  30.6  86.3  29.9  86.3
ARM  Placebo Part 1  7  5  71.4  29.0  96.3  35.9  91.8  34.9  91.5

11. Multiplicity, Missing Data and Analysis Populations

The study record lists multiple outcomes, including the Part 1 adverse-event endpoint, pharmacokinetic measures, and pharmacodynamic measures. It reports 22 outcome measures and 17 posted secondary outcomes. When many outcomes are examined, the chance of at least one apparently notable result arising by chance can increase. In general, a prespecified testing hierarchy or multiplicity adjustment can help address this issue. The registry record does not report a multiplicity strategy, a testing hierarchy, or a statistical analysis plan. It also reports 0 registered analyses, so the intended inferential procedures cannot be checked against posted analysis details.

The primary outcome population is stated as all randomized Part 1 participants. However, the record does not describe how missing primary outcome data were handled, whether any participants lacked endpoint information, or whether the reported percentages use a particular missing-data convention. The posted cohort sizes are available, but the analytic denominator and any exclusions are not explained beyond the named population. A missing-data method should not be inferred from the percentages.

The record also does not explain how the Part 1 cohorts were allocated or whether subgroup or dose comparisons were prespecified. Without a stated analysis plan, it is not possible to determine whether the reported results represent the planned analyses or selected summaries. These gaps do not invalidate the descriptive figures, but they limit evaluation of their inferential meaning and their comparability across outcomes.

12. 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: radius fracture (14.3%), hepatic enzyme increased (14.3%).

Serious adverse events are listed separately from other adverse events. In Part 1, the serious-event counts are 0 of 6 at QBM076 25 mg twice daily, 0 of 6 at QBM076 75 mg twice daily, 0 of 8 at QBM076 150 mg twice daily, and 1 of 7 with placebo. In Part 2, the listed counts are 2 of 14 for QBM076 150 mg twice daily and 0 of 7 for placebo. These are descriptive counts; they do not establish that treatment caused or prevented an event.

The record names Radius fracture and Hepatic enzyme increased among the top serious-event terms, with each listed as 14.3%. The registry entries do not identify the group associated with either term or provide further case descriptions. Death counts are not reported in the registry record. The seriousness and clinical context of individual events, timing, relatedness assessments, and resolution are not reported in the registry record.

Serious-event counts are distinct from the primary endpoint, which reports the percentage of participants with any adverse event in Part 1. Sparse counts can be difficult to compare, and the registry record gives no confidence intervals or statistical test for serious adverse events. These figures should therefore be read as a safety description of the observed groups, not as a definitive comparative estimate.

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

The posted results describe adverse events observed during the study, including the Part 1 percentages over 14 days and serious-event counts in both parts. They show what was recorded in the small groups enrolled under this study design. The Part 1 percentages vary across the three QBM076 dose cohorts and placebo, but no formal comparison or estimate of uncertainty for the primary outcome is reported in the registry record.

These figures do not establish a causal difference between QBM076 and placebo. Randomization is a design feature intended to support fair comparisons, but a reliable comparative conclusion also depends on the prespecified analysis, outcome completeness, and uncertainty around estimates. The registry record does not report the statistical analysis methods, confidence intervals, or handling of missing primary outcome data. The small cohort sizes further constrain precision.

The primary outcome is a safety and tolerability measure, not a direct measure of COPD efficacy. Part 2 is described as an efficacy study, but the primary result under discussion is specifically the Part 1 adverse-event endpoint. Safety counts from Part 2 do not substitute for an efficacy result, and Part 1 and Part 2 should not be merged into one comparison because their treatment periods and stated study purposes differ.

The record's terminated status is relevant context, but it does not explain why the study ended or whether termination affected the planned analyses. That reason is not reported in the registry record. The result should therefore be treated as a limited descriptive account rather than a complete basis for evaluating the study's overall objectives. It neither establishes that QBM076 is beneficial nor establishes that it is harmful; it reports observed outcome summaries without the inferential detail required for those conclusions.

14. Why This Trial Matters Statistically

This trial illustrates how design and reporting details shape the interpretation of clinical results. It was randomized, triple-masked, and parallel-group, but the primary Part 1 groups were small. A percentage can look straightforward while still carrying considerable uncertainty when it is based on few participants. Reporting the cohort sizes beside the percentages is essential context for reading the observed values.

The study also separated safety and tolerability assessment in Part 1 from an efficacy-focused Part 2. That distinction matters: an adverse-event percentage and an efficacy measure address different questions, and a result from one part cannot automatically answer the objective of the other. The registry record identifies several pharmacokinetic and pharmacodynamic outcomes as well, highlighting that a study can collect multiple kinds of evidence without every measure serving as the primary clinical question.

For statistical interpretation, the absence of a posted inferential analysis is important. The registry record gives descriptive outcome values but does not report confidence intervals, tests, a multiplicity approach, or missing-data procedures. Those details would help readers judge uncertainty, the role of chance, and whether the reported comparisons align with an analysis plan. Their absence means the observed percentages should be interpreted as descriptive findings.

Finally, the terminated status and the short Part 1 observation period provide context for the scope of the record. Neither explains the reason for termination or the completeness of planned analyses. The study is useful statistically as an example of why outcome definitions, analysis methods, precision, and transparent reporting all matter alongside the numerical results.

15. 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 primary outcome covers a 14-day period and the Part 1 cohorts are small, limiting how precisely the reported percentages characterize event occurrence. The registry record does not provide confidence intervals or a formal comparison of QBM076 with placebo. As a result, the data do not quantify uncertainty around the observed group differences.

The analysis plan is not described in the registry record. In particular, the record does not report the statistical method for the primary endpoint, how missing outcomes were handled, whether covariates were used, or how multiple outcomes were addressed. Although the primary population is identified as all randomized Part 1 participants, the detailed analysis set is not explained.

The study's status is terminated, but the reason for termination and its effect on completion of planned outcomes are not reported in the registry record. No explanation is given for whether the study stopped early or whether any analyses were changed. These details should not be inferred from status alone.

The serious-event terms are reported with percentages but are not assigned to specific groups in the registry record described. Death counts and additional clinical details about the serious events are not reported in the registry record. Part 2 safety observations also come from a different treatment period and study aim than the Part 1 primary endpoint, so they cannot resolve the limitations of the Part 1 comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Safety, Tolerability and Efficacy Study in Chronic Obstructive Pulmonary Disease (COPD) Patients With QBM076. — NCT01972776.
• Registry record last updated 2016-03-24; status last verified 2016-02.
• Results first posted 2016-03-24.
• 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.

19. Record Summary

NCT01972776 is a randomized, triple-masked, parallel-group Phase 2 study of QBM076 and placebo in participants with COPD. It had two parts: Part 1 assessed safety and tolerability across QBM076 dose cohorts over 14 days, and Part 2 assessed efficacy using QBM076 150 mg twice daily or matching placebo for 8 weeks. The registry records enrollment of 48, status as terminated, and primary completion in 2015-05.

The primary outcome was the percentage of Part 1 participants with adverse events. Posted percentages range from 33.0% to 71.0% across the QBM076 cohorts and placebo. Serious adverse events are listed by group for both parts. The registry record does not report inferential analyses, confidence intervals, the reason for termination, or detailed methods for missing data and multiplicity. The results are therefore descriptive and should be interpreted with attention to the small groups and limited analysis detail.