A Study in Healthy Men to Test Whether Food Influences the Amount of BI 3731579 in the Blood: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in Healthy Men to Test Whether Food Influences the Amount of BI 3731579 in the Blood (NCT06861829), a randomized phase 1 study. The primary outcome is Area Under the Concentration-time Curve of BI 3731579 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz).

2. Clinical Question

3. Trial Design

This was a phase one, randomized, open-label, two-period, two-sequence crossover trial of BI 3731579 in healthy male subjects. The registry describes the trial as completed and lists enrollment of 12. In a crossover design, participants receive more than one treatment condition in separate periods, so the comparison can account for participant-level differences. That is a general feature of crossover designs; the registry’s posted summary does not give enough detail to verify how complete paired observations were handled in the reported analysis.

The two conditions were fed and fasted administration of a single oral dose. The fasted condition followed an overnight fast of at least 10 hours. The fed-condition description specifies a high-calorie, high-fat breakfast after an overnight fast of at least 10 hours. The descriptions also mention 240 mL of water, but the available text is truncated and does not establish every administration detail for both conditions.

Randomization assigned participants to the sequence described as fasted then fed or fed then fasted. The trial was open label, meaning masking was not used. This feature is relevant to expectations and assessments that could be influenced by knowledge of the condition, though the primary endpoint is a measured concentration-based pharmacokinetic outcome.

The registry reports 12 observations in each condition for the primary endpoint. It does not report the randomization procedure, period-specific enrollment or completion, washout details, protocol deviations by sequence, or the planned sample-size justification. Those design details 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: All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Period 1

Washout

Period 2

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetics (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he/she contributed only one PK parameter value for one period to the statistical assessment.

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): The treated set included all subjects who were treated with at least one dose of trial drug.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Concentration-time Curve of BI 3731579 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz), measured over Within 3 hours (hrs) before and 15 minutes (min), 30 min, 1 hrs, 1.5 hrs, 2 hrs, 2.5 hrs, 3 hrs, 3.5 hrs, 4 hrs, 4.5 hrs, 5 hrs, 6 hrs, 8 hrs, 12 hrs, 24 hrs, 48 hrs, and 72 hrs after first drug administration.

The primary endpoint was the area under the plasma concentration-time curve for BI 3731579 from time 0 to the last quantifiable data point, abbreviated AUC0-tz. Its unit is hours*nanomoles/Liters (h*nmol/L). The registry describes blood sampling from within 3 hours before administration through 72 hours after the first drug administration, with multiple scheduled post-administration timepoints.

AUC represents accumulated drug concentration over time across the measured interval. It is used in pharmacokinetic studies to describe overall exposure, rather than the concentration at a single sampling time. AUC0-tz ends at the last quantifiable concentration, so its value depends in part on the measured concentration profile and the endpoint’s quantification boundary. The registry also lists AUC from time 0 extrapolated to infinity as a secondary outcome.

The primary result is presented as a geometric least-squares mean for each condition, alongside a reported geometric mean ratio. Geometric summaries are commonly used for pharmacokinetic measures because exposure values can be right-skewed and treatment comparisons are often expressed as ratios. The registry does not report the individual concentration profiles, the arm-level standard errors, or details of the model used to obtain the least-squares means.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is summarized using geometric least-squares means. A least-squares mean is a model-based estimate of a group mean, adjusted for the terms included in the statistical model. The registry identifies the summary type but does not report the model terms or the full analysis specification. The label therefore does not establish which adjustments were made or how the crossover structure was represented.

Geometric summaries are useful for positive-valued measures that may vary multiplicatively. Rather than treating equal absolute changes as the natural scale, comparisons on a logarithmic scale describe proportional differences. Exponentiating a mean on the log scale returns a geometric mean on the original scale. This is a general explanation of the method; the registry does not state the precise transformation or estimation steps used for this analysis.

The reported comparison is a geometric mean ratio for fed versus fasted conditions. A ratio expresses one condition relative to another, rather than their absolute difference. A reference value of 100 is the no-ratio-difference point when the result is reported on a percentage scale. The posted estimate is 90.04, and its 90% confidence interval is 84.26 to 96.22. The registry does not give a p-value for this comparison.

A confidence interval describes the uncertainty of an estimated parameter under the statistical model and its assumptions. In repeated use of the same procedure, intervals constructed at a stated confidence level would cover the target parameter at that rate, under the model’s conditions. For an individual trial, the interval is not a probability statement that the true value lies within its particular limits, nor does it describe the range of individual responses. Here, the interval quantifies uncertainty in the reported ratio; it does not include uncertainty from every possible design or measurement limitation.

In general, crossover analyses must account for the fact that observations from the same participant are related. The within-participant comparison can reduce variability due to stable differences between participants, but only when the analysis and data structure support that comparison. Period and sequence effects can also matter in crossover studies. The registry record names a two-period, two-sequence crossover design but does not report how these terms were handled, whether carryover was assessed, or what washout procedure was used. It is not possible to infer those methods from the design label alone.

The arm-level results list geometric least-squares means but no arm-specific spread or confidence interval. The ratio interval offers an uncertainty measure for the comparison, while the absence of further model output limits independent assessment of the estimate. The registry does not report individual observations, standard errors for the displayed arm estimates, or a detailed statistical analysis plan. These omissions make it difficult to assess model fit, influential observations, or sensitivity to alternative analysis choices.

Over-dispersion is a general concern when data vary more than a chosen statistical model expects. It can make standard errors too small if the model underestimates variability, and can affect confidence intervals and tests. Its relevance depends on the outcome distribution and analysis model. The registry does not report a model diagnostic or an over-dispersion assessment for this endpoint, so no conclusion about that issue can be drawn.

Multiplicity arises when several outcomes or comparisons are examined. Repeated testing can increase the chance of at least one apparently unusual result if no adjustment or hierarchical testing plan is used. The registry lists three outcome measures and three analyses, but a multiplicity strategy is not reported in the registry record. The primary endpoint should be distinguished from the listed secondary outcome; the posted record identifies AUC0-∞ as a secondary outcome but does not provide its result in the registry record for this analysis.

Any sample-size values used for planning are illustrations based on assumptions, not observed power for this completed trial. A planning illustration describes the sample size that a hypothetical future study might require under its stated assumptions. It does not measure the probability that the present study detected an effect, and it cannot replace the trial’s observed estimate and confidence interval. The registry does not report the trial’s own sample-size justification.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s geometric mean ratio as 90.04, with a 90% confidence interval from 84.26 to 96.22. The estimate is presented for the fed-versus-fasted comparison of the primary AUC0-tz endpoint. No p-value is reported for this analysis.

The registry’s discrepancy indicator is false, so no discrepancy is flagged between the sponsor analysis and a recalculation. The registry entries available for this interpretation do not include a separate recalculated estimate or confidence interval; none can be compared numerically with the sponsor result. The sponsor’s reported analysis is therefore the posted comparative estimate to interpret. It should be read with its confidence interval and the limitations of the reported methods, rather than as a result independently verified from participant-level data.

The arm-level estimates are also reported as geometric least-squares means, but their dispersion measures and detailed model specification are not reported. Thus, the sponsor’s ratio and interval are the principal reported quantities for judging the precision of the comparison, while full reproduction of the analysis is not possible from the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The record identifies AUC0-tz as the primary endpoint and lists AUC0-∞ as a secondary outcome. It also records three outcome measures and three analyses. Further descriptions and results for the additional measures are not available in the registry record. A multiplicity adjustment, testing hierarchy, or prespecified approach to interpreting multiple outcomes is not reported in the registry record.

Multiplicity matters because examining several outcomes or comparisons can make isolated results appear more compelling than they would under a single prespecified test. This is a general statistical concern; it does not establish that the analysis used an inappropriate method. Without the analysis plan, it is not possible to determine whether testing was adjusted, whether the outcomes were considered confirmatory or exploratory, or how any secondary findings were intended to be interpreted.

The primary endpoint population is described as a pharmacokinetic parameter analysis set. The available text states that it included treated-set subjects with at least one primary pharmacokinetic endpoint, excluding subjects because of relevant protocol deviations or pharmacokinetic non-evaluability. The description is truncated, and the full definition is not reported in the registry record. The numbers excluded, reasons for exclusion, and handling of missing measurements are not reported in the registry record.

Although the design is crossover, the results list 12 observations in each treatment condition. The number of complete paired observations used for the ratio is not reported in the registry record. The record also does not state how missing period data were handled, whether any imputation was used, or whether sensitivity analyses were conducted. These details matter because incomplete observations may affect the estimate and its precision, especially when the analysis relies on within-participant comparisons.

The protocol, statistical analysis plan, sample-size justification, interim analyses, and prespecified missing-data procedures are not reported in the registry record. Their absence limits assessment of whether the displayed analysis fully follows a prespecified plan.

12. 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 posted safety figures list zero serious adverse events in the fasted condition and zero in the fed condition. Deaths are listed as zero in each condition. These are the registry’s reported counts for the groups at risk; they do not show that the study had no non-serious adverse events.

Other adverse events are listed for 3 subjects in the fasted condition and 2 subjects in the fed condition. The record does not provide the event terms, severity breakdown, timing, or a detailed account of how events were attributed to treatment. The list of top serious-event terms is empty, consistent with the reported serious-event counts, but does not provide further safety detail.

These figures are descriptive counts from a small phase one study in healthy male subjects. They are not a comparative safety analysis with reported uncertainty, and the registry does not report a statistical test of adverse-event differences. The counts should not be interpreted as evidence that rare or delayed events could not occur, or as a full characterization of safety. They describe the adverse-event information posted for this study and population.

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

The primary finding is a reported geometric mean ratio of 90.04 for fed versus fasted AUC0-tz, with a 90% confidence interval from 84.26 to 96.22. This gives a comparative estimate of plasma exposure under the two administration conditions in the analyzed study population. The confidence interval conveys uncertainty around that estimate under the sponsor’s analysis.

The result does not establish the clinical importance of the observed pharmacokinetic contrast. The registry does not report a clinical outcome, a clinical threshold for interpreting this ratio, or a p-value. Statistical uncertainty and clinical relevance are distinct questions: a numerical estimate can be described precisely without establishing whether it matters for a clinical decision.

The result is not a direct comparison of clinical benefit or harm, and it does not show whether BI 3731579 is effective for any condition. The study enrolled healthy male subjects and evaluated a single oral dose in fed and fasted conditions. It does not establish the same exposure pattern in other populations, with repeated dosing, or under other food conditions.

The endpoint is AUC0-tz, not every aspect of pharmacokinetics. The posted result does not answer questions about peak concentration, the timing of peak concentration, or the secondary AUC0-∞ result. The record’s limited reporting of model details, missing-data handling, and population definition also constrains how thoroughly the estimate can be independently evaluated.

The safety figures describe the adverse events recorded during the trial, including zero reported serious adverse events in each condition and other adverse events in both conditions. They do not establish the absence of risk. Overall, the record supports a narrowly framed interpretation: an estimated fed-versus-fasted difference in a plasma exposure measure, with reported statistical uncertainty and important limits on generalization and independent verification.

14. Why This Trial Matters Statistically

This study illustrates how a crossover design can be used to compare pharmacokinetic conditions. In general, crossover trials allow participants to receive multiple conditions, which can make each participant a reference for their own response. That design can be efficient for pharmacokinetic questions, where measurements are tied to defined dosing conditions. Its interpretation still depends on complete data, appropriate handling of within-participant correlation, and attention to period and sequence effects.

The result also illustrates why ratios and confidence intervals are central to pharmacokinetic interpretation. Geometric mean ratios express relative exposure, and the confidence interval communicates uncertainty around that relative estimate. Reporting the interval alongside the point estimate gives readers more information than the point estimate alone. The registry does not report a p-value or detailed model specification, emphasizing that a single summary cannot answer every question about statistical evidence or reproducibility.

Another statistical lesson is the distinction between the prespecified primary endpoint and other measured outcomes. The registry identifies AUC0-tz as primary and lists AUC0-∞ as secondary, but the additional outcome results and multiplicity strategy are not reported in the registry record. Without that context, secondary findings would need cautious interpretation.

Finally, this record shows the limits of registry-level summaries. Arm estimates and a ratio interval can convey the main comparison, but missing information on paired records, analysis details, exclusions, and handling of missing observations restricts independent assessment. Transparent reporting of these elements is important for evaluating precision and understanding how a crossover estimate was obtained.

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 available results are limited to a single-dose pharmacokinetic comparison in healthy male subjects. They do not describe other populations or repeated administration. The arm descriptions are truncated, so the full administration procedures for both conditions are not reported in the registry record.

The registry reports geometric least-squares means and a geometric mean ratio, but it does not report the model specification, model diagnostics, or detailed estimation procedure. Arm-level dispersion measures are not reported. The confidence interval provides comparative precision, but the absence of individual-level data and further model output prevents independent reproduction of the estimate.

The primary analysis population description is incomplete. The number of subjects excluded from the pharmacokinetic analysis set, the reasons for exclusions, and the number of complete paired observations are not reported in the registry record. Missing-data methods and sensitivity analyses are also not reported in the registry record.

The record does not report the washout procedure, whether period or sequence effects were evaluated, or how these features were handled in the analysis. The trial’s sample-size justification and any interim analyses are not reported in the registry record. A multiplicity strategy for the listed outcome measures and analyses is likewise not reported.

The safety summary provides counts for serious and other adverse events, but the detailed event terms and severity information are limited. These constraints mean the posted results are best interpreted as a focused estimate of AUC0-tz under the study conditions, not as a comprehensive account of pharmacokinetics or safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study in Healthy Men to Test Whether Food Influences the Amount of BI 3731579 in the Blood — NCT06861829.
• Registry record last updated 2026-08-11; status last verified 2026-06.
• Results first posted 2026-08-11.
• 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

The registry describes a completed, randomized, open-label, two-period, two-sequence crossover trial of BI 3731579 in healthy male subjects. It lists enrollment of 12 and evaluates single-dose administration in fed and fasted conditions.

The primary endpoint is plasma AUC0-tz. The reported geometric mean ratio for fed versus fasted conditions is 90.04, with a 90% confidence interval from 84.26 to 96.22. The registry lists zero serious adverse events and zero deaths in each condition, alongside other adverse events in both conditions.

Detailed analysis methods, complete population accounting, missing-data handling, and multiplicity procedures are not reported in the registry record. The result is a pharmacokinetic comparison in the study population, not a clinical efficacy finding.