This Study Tests the Safety, Tolerability and How Different Doses of BI 1265162 Are Taken up in the Body of Healthy Men: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for This Study Tests the Safety, Tolerability and How Different Doses of BI 1265162 Are Taken up in the Body of Healthy Men (NCT03349723), a randomized phase 1 study. The primary outcome is Percentage of Participants With Drug-related Adverse Events (AEs).

2. Clinical Question

The main statistical focus is descriptive: the primary outcome is reported as a percentage within each dose group and the placebo group. The registry record does not provide a single pooled dose-versus-placebo estimate, or an inferential comparison across those groups. Therefore, the posted percentages should be read as group-specific observations rather than as evidence of a tested difference between BI 1265162 and placebo.

This question is specific to healthy male volunteers receiving single inhaled doses. It does not address repeated dosing, other populations, or clinical benefit. The record describes safety, tolerability, and pharmacokinetics as the objectives, but does not report numerical results for the named pharmacokinetic outcomes.

3. Trial Design

The registry record identifies this as a phase 1, randomized, single-blind, parallel-group trial. Its official title describes it as partially randomized and placebo-controlled. The record does not explain which parts of allocation were randomized or identify who was blinded. Participants were assigned to groups receiving BI 1265162 at one of seven labeled dose levels or matching placebo. The arm-level results list 6 participants in each BI 1265162 group and 14 in the placebo group.

The trial studied single rising inhaled doses in healthy male volunteers. This design allows safety outcomes to be described separately across dose groups and against a placebo group. The parallel model indicates that groups are reported as distinct arms; the record does not describe crossover periods or repeated treatment periods. Further details of dose escalation, cohort sequence, or decision rules are not reported in the registry record.

The registry lists enrollment of 57. The listed primary outcome concerns the percentage of participants with drug-related adverse events, assessed from drug administration through the end-of-trial examination, up to 9 days. The treated set included participants who had received at least one dose of trial medication. The trial status is completed, with a start date of 2017-11-23 and a primary completion date of 2018-03-05.

Safety and tolerability were the primary objective. The secondary objective was to explore pharmacokinetics after single dosing. The named secondary measures are maximum measured concentration of BI 1265162 in plasma (Cmax) and area under the plasma concentration-time curve over the interval 0 to 1 Hour post-dose (AUC0-1). Numerical results for these measures are not reported in the registry record.

The sample-size justification, allocation concealment procedures, detailed masking procedures, and prespecified statistical analysis plan are not reported in the registry record. The enrollment figure and arm sizes describe the recorded trial, but do not by themselves establish the intended precision or rationale for the planned sample size.

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: All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensure that all participants met all inclusion/exclusion criteria. Participants were not to be randomized to trial treatment if any one of the specific entry criteria were not met.

Only the first 6 of 8 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Treated set(TS): This subject set included all subjects who had received at least 1 dose of trial medication.

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: Treated set(TS):This subject set included all subjects who had received at least 1 dose of trial medication.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Drug-related Adverse Events (AEs), measured over From drug administration until end of trial examination, up to 9 days.

The primary endpoint is the percentage of participants with drug-related adverse events (AEs). It is a participant-level summary: it describes the proportion of people in an arm who were recorded as having at least one AE judged to be drug-related, rather than counting every event as a separate participant. The endpoint timeframe runs from drug administration until the end-of-trial examination, up to 9 days. The analysis population is the treated set, defined as participants who received at least one dose of trial medication.

This kind of outcome is used in a safety and tolerability trial to describe how often participants experience events considered related to the study medication during the specified observation period. The arm-specific percentages offer a compact description of observed experience at each dose and with placebo. They do not, on their own, establish whether event frequencies differ reliably between groups; that requires an appropriate comparative analysis and a measure of uncertainty.

The registry reports 0.0% drug-related AEs for the 3, 10, 30, 600, and 1200 Microgram BI 1265162 groups and for placebo. It reports 16.7% for both the 100 and 300 Microgram groups. Each BI 1265162 arm has 6 participants, while the placebo arm has 14. No confidence intervals for the percentages are reported in the registry record.

The endpoint is distinct from the separate summary of serious adverse events and other adverse events. Those summaries count affected participants within their own categories and should not be treated as interchangeable with the primary drug-related AE percentage.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a percentage, which expresses the number of participants meeting an outcome definition relative to the number in the relevant group. In this trial, the reported outcome is the percentage with drug-related AEs in each arm. The accompanying arm sizes show that the dose groups were small. When only a few participants are observed, a change in the experience of one participant can substantially affect an arm's percentage. This is a general property of percentages based on small denominators, not a conclusion about the cause of any particular event.

What does a confidence interval add?

As a general statistical concept, a confidence interval describes uncertainty around an estimated quantity under a specified method and assumptions. For a percentage, it can show that the underlying event frequency is compatible with a range of values, rather than implying that the observed percentage is known exactly. A confidence interval is especially useful when the estimate is based on a small group. The registry record does not report confidence intervals for the primary outcome, so the precision of each arm's percentage cannot be assessed from an interval in the posted results.

Why distinguish an arm summary from a comparison?

An arm-specific percentage answers a descriptive question about the observed participants in that group. A comparison asks whether the outcome frequency differs between treatment and comparator groups, and by how much. Comparative results ordinarily require a stated estimand or contrast, a method for handling the outcome, and an uncertainty measure. The registry record does not provide an estimable two-arm comparison for this count-type endpoint; it states that values are missing or not estimable for a two-arm comparison. Consequently, the arm percentages should not be recast as treatment effects or as formal evidence of a difference from placebo.

The distinction matters even when one arm has a nonzero percentage and another has a reported 0.0%. Observed percentages are affected by sampling variability. Without a comparison estimate and uncertainty information, readers cannot judge how precisely the groups differ or whether the observed pattern is compatible with a range of underlying event frequencies. The absence of an estimate is not itself evidence that groups are equivalent.

What does the group structure permit?

The record presents seven separate BI 1265162 dose groups and a placebo group. The recorded allocation is randomized, while the official title describes the study as partially randomized. The results are not reduced to one comparison, and there is no single treatment-versus-placebo summary spanning all dose groups. A pooled estimate would answer a different question and would require a rationale for combining dose levels. No such rationale is reported in the registry record. The dose-specific summaries preserve the fact that exposure levels were distinct, but they do not provide a formal dose-response analysis.

The listed primary parameter is a number, reported as a percentage of participants. That is different from a continuous outcome such as a concentration measurement, where a mean or median and a measure of spread might be reported. For the primary outcome, no dispersion estimate is listed. General statistical methods for binary or count outcomes can include exact or approximate intervals and comparative models, but the registry record does not identify a method used to estimate comparative effects. It would be inappropriate to infer a specific test from the percentages alone.

How should the pharmacokinetic outcomes be understood?

Cmax refers to the maximum measured plasma concentration, while AUC0-1 describes exposure over the stated interval from 0 to 1 Hour post-dose. In general, these measures characterize different features of a concentration-time profile: a peak level and accumulated exposure over an interval. Their interpretation depends on the measurement schedule, assay, and analysis method. Those details and numerical results are not reported in the registry record. The named outcomes therefore establish what was intended to be explored, but do not allow a quantitative pharmacokinetic interpretation.

More generally, concentration and exposure data may be skewed or vary substantially across participants. Statistical methods may account for such features when supported by the data and specified analysis plan. No distributional summaries, transformation methods, or pharmacokinetic modeling details are reported in the registry record. None should be assumed.

What do sample-size calculations mean?

A planning calculation is a design illustration based on assumptions about an effect, variability, significance level, allocation, and analysis method. It is not a measure of what the completed trial observed and is not “observed power.” General power calculations describe the chance that a prespecified procedure would detect an assumed effect under its assumptions. The registry record does not report the trial's own sample-size justification. Any planning illustration based on the observed effect should be distinguished from the original design rationale and cannot replace an uncertainty estimate for the actual results.

The trial's listed arm sizes and enrollment describe how many participants were recorded in the study and in the endpoint groups. They do not reveal how the target enrollment was chosen, whether a formal stopping rule was used, or whether interim analyses were planned. Those design details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The trial has several dose groups, a placebo group, a primary safety endpoint, and named secondary pharmacokinetic outcomes. Considering many outcomes or multiple group comparisons can raise multiplicity concerns: the more inferential questions addressed, the greater the chance of obtaining at least one apparently unusual result by chance if each is tested without adjustment. This is a general statistical concern, not a claim that a particular adjustment was or was not applied in the analysis.

The registry record does not report a multiplicity strategy, a hierarchy for testing outcomes, or a prespecified plan for comparing each dose with placebo. It also does not report an inferential test for the primary endpoint. Because the posted primary results are arm-specific percentages rather than comparative estimates, they should be interpreted descriptively and not as a set of adjusted or unadjusted significance tests.

The primary population is the treated set, including participants who received at least one dose of trial medication. The record does not report how missing outcome data were handled, whether any participants were excluded from particular outcome analyses, or whether all randomized participants were included in any other analysis population. The arm-level sizes are reported, but they do not document the completeness of all outcome assessments or explain missingness.

Interim analyses, stopping rules, and the detailed statistical analysis plan are not reported in the registry record. Without those details, the analysis procedures and their relationship to the original design cannot be reconstructed. These omissions limit assessment of multiplicity control and missing-data handling; they do not change the descriptive values reported for the primary endpoint.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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

The serious adverse-event summary reports 0 serious events among participants at risk in every BI 1265162 dose group and in placebo. The reported number of deaths is also 0 in every group. These are counts within the recorded trial and follow-up, not estimates of the frequency of rare events over longer periods.

The separate “other adverse events” counts are 1 in the 3 Microgram group, 0 in the 10 Microgram group, 1 in the 30 Microgram group, 1 in the 100 Microgram group, 2 in the 300 Microgram group, 0 in the 600 Microgram group, 1 in the 1200 Microgram group, and 2 in placebo. The numbers at risk are 6 in each BI 1265162 group and 14 in placebo. These are participant counts in the event summary, not the primary endpoint percentages.

“Other adverse events” should not be read as synonymous with drug-related events. The primary endpoint specifically concerns events classified as drug-related, while the safety summary separates serious events and other events. The record does not provide serious-event terms, and no serious-event terms are listed. The small groups and observation period up to 9 days limit what can be inferred from zero reported serious events.

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

The results describe the recorded experience of healthy male volunteers after single inhaled doses of BI 1265162 or matching placebo. For the primary drug-related AE endpoint, the posted percentages are 16.7% in the 100 and 300 Microgram groups and 0.0% in the other listed dose groups and placebo. The results also report no serious adverse events and no deaths in any group during the trial record's observation period.

These observations do not establish that BI 1265162 caused or prevented an event, nor do they demonstrate that any dose is safer or less safe than placebo. The registry record does not provide a comparative effect estimate or confidence interval for the primary endpoint. With 6 participants per BI 1265162 group and 14 in placebo, the observed percentages are limited descriptions of these groups; they do not precisely determine the event frequency that might be seen in a larger population.

The outcome concerns events classified as drug-related and observed within a timeframe of up to 9 days. It does not describe longer-term outcomes or repeated administration. The population was healthy male volunteers, so these findings do not directly characterize other populations or clinical settings. The record's stated objective included pharmacokinetic exploration, but numerical Cmax and AUC0-1 results are not reported in the registry record.

Zero observed events in a group should be interpreted narrowly: none were recorded for that outcome among the participants included during the specified follow-up. It does not prove that the event cannot occur. Likewise, the two nonzero percentages do not by themselves demonstrate a dose-related pattern, particularly because the higher dose groups have reported percentages of 0.0% and no formal trend estimate is reported.

The appropriate takeaway is a descriptive account of the posted safety results in a small, early-phase single-dose study. The results do not provide a precise comparative estimate, establish a causal treatment effect, or support conclusions beyond the studied trial conditions.

13. Why This Trial Matters Statistically

This trial illustrates how early-phase safety results can be informative while remaining statistically limited. Reporting the percentage with drug-related AEs separately for each dose preserves the differences among the dose groups and makes the observed pattern visible. At the same time, the small arm sizes mean that the percentages should be understood as summaries of the participants observed, not as highly precise estimates of event frequency.

The record also shows why descriptive outcomes and inferential comparisons should not be conflated. A percentage in a dose group and a percentage in placebo are not, by themselves, a treatment effect. Comparative estimates and uncertainty measures would be needed to quantify the difference and its precision. The registry record does not report those estimates for this count-type endpoint, so the evidence should remain at the descriptive level.

Separating the primary drug-related AE measure from summaries of serious and other adverse events is important for interpretation. The categories answer different questions: whether events were considered drug-related, whether they were serious, and how many participants had other events. Keeping those distinctions clear prevents an event count from being assigned a relationship that the record does not state.

The trial also demonstrates the limits of a short, single-dose study for broad safety conclusions. Its results concern healthy male volunteers and observation through an end-of-trial examination, up to 9 days. The absence of serious events in the posted groups is a useful description of what was observed, but it cannot settle questions about rare events or outcomes outside the study conditions.

Finally, objectives and results are not interchangeable. Cmax and AUC0-1 are named as secondary outcomes, but numerical results are not reported in the registry record. Acknowledging that gap keeps interpretation aligned with the quantities that can actually be assessed.

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 main limitation is the size of the dose groups: each BI 1265162 group includes 6 participants, and placebo includes 14. Percentages from groups of this size are sensitive to individual participant outcomes. The record does not provide confidence intervals or another uncertainty measure for the primary endpoint, which limits assessment of precision.

The primary results are descriptive, and a two-arm comparison is not reported as estimable in the registry record. There is no reported effect estimate comparing individual doses with placebo, no formal dose-response analysis, and no reported inferential test for the primary endpoint. The observed pattern therefore cannot establish a difference between groups or a trend across doses.

The population and exposure are narrow: healthy male volunteers received single inhaled doses, and the stated endpoint timeframe extends up to 9 days. The findings do not characterize repeated dosing, longer follow-up, or populations not studied. Numerical pharmacokinetic results for Cmax and AUC0-1 are not reported, despite those outcomes being named.

Several design and analysis details are also absent. The registry record does not report the sample-size justification, detailed statistical analysis plan, multiplicity strategy, missing-data handling, interim analyses, or stopping rules. It describes the study as partially randomized in its official title but does not explain the allocation process in detail or identify who was blinded. These gaps limit evaluation of how the analyses were planned and conducted, without changing the reported arm-level counts and percentages.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: This Study Tests the Safety, Tolerability and How Different Doses of BI 1265162 Are Taken up in the Body of Healthy Men — NCT03349723.
• Registry record last updated 2022-04-11; status last verified 2022-03.
• Results first posted 2022-02-23.
• 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

NCT03349723 is a completed phase 1, randomized, single-blind, parallel-group, placebo-controlled trial of single rising inhaled doses of BI 1265162 in healthy male volunteers. The registry lists 57 participants enrolled. The primary objective was safety and tolerability; the secondary objective was pharmacokinetic exploration.

The primary outcome was the percentage of participants with drug-related AEs from administration through end-of-trial examination, up to 9 days, in the treated set. The reported percentage was 16.7% in the 100 and 300 Microgram groups and 0.0% in the remaining dose groups and placebo. No serious adverse events or deaths were reported in any group.

The record does not report a comparative estimate for the primary outcome, numerical results for the named pharmacokinetic measures, or key details of the statistical plan. The available results support a descriptive reading of the trial groups, not a precise comparative or dose-response conclusion.