A Study in Healthy People to Test How BI 425809 is Taken up in the Body When Taken With or Without Food: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in Healthy People to Test How BI 425809 is Taken up in the Body When Taken With or Without Food (NCT05347004), a randomized phase 1 study. The primary outcome is Area Under the Concentration-time Curve of BI 425809 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz).

2. Clinical Question

The clinical question is about pharmacokinetics: the pattern of drug concentration in plasma over time. It is not a question about a clinical benefit or health outcome. The primary endpoint captures cumulative plasma exposure over the observed, quantifiable portion of the concentration-time profile. The registry reports adjusted geometric least-squares means for the two treatment conditions and an adjusted geometric mean ratio comparing the fed condition with the fasted condition.

Because this was a crossover study, each participant was assigned to a sequence involving both conditions, rather than being assigned to only one of two independent groups. The two listed sequences were without food followed by with food, or with food followed by without food. This structure permits a within-participant comparison, while the analysis also accounts for sequence and period. The registry does not report a separate clinical question about efficacy, nor does it report a food-related clinical outcome. The interpretation should therefore remain focused on the stated pharmacokinetic measure and the precision of its estimated treatment comparison.

3. Trial Design

This was a Phase 1, randomized, open-label, two-period, two-sequence crossover trial in healthy people. The registry describes 16 participants as enrolled. The study is marked completed, with a start date of 2022-10-25 and a primary completion date of 2022-12-28. Boehringer Ingelheim is listed as the sponsor.

The treatment conditions were BI 425809 without food, designated the reference treatment, and BI 425809 with food, designated the test treatment. Participants were assigned to one of two sequences: reference followed by test, or test followed by reference. The registry identifies the study as open-label, meaning masking was not used. It does not report details about the allocation procedure beyond randomized assignment.

A crossover design compares treatment conditions within participants across periods. This can account for stable differences between participants in the treatment comparison, but the treatment contrast may also depend on how period and sequence are handled. The posted primary-outcome description says the analysis accounted for sequence, subjects within sequences, period, and treatment. It treats subjects within sequences as random and the other listed effects as fixed. The registry does not report a washout interval, the length of each period, or further operational details about sequence conduct.

The primary endpoint was AUC0-tz, the area under the plasma concentration-time curve from 0 to the last quantifiable data point. The record also lists AUC0-∞ as a secondary outcome. Three outcome measures and three analyses are indicated overall, while one secondary outcome is identified by name. Additional detail about the remaining outcome measures and analysis methods is not reported in the registry record. The arm-level primary endpoint summaries include 15 participants in each treatment condition. The record does not explain why those analysis counts are below the enrollment count of 16.

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.

Treatment period 1

Washout period

Reasons for not completing this period:

Treatment period 2

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) parameter analysis set: All subjects who were treated with at least one dose of BI 425809 and who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. One subject from the BI 425809 without food (R) group was excluded due to abnormal BI 425809 values prior to its administration.

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 analysis set included all subjects who were treated with at least one dose of trial medication.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Concentration-time Curve of BI 425809 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz), measured over From within 2 hours prior and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 47, 71, 119, 167 and 215 hours after BI 425809 administration..

The primary endpoint, AUC0-tz, measures the area under the plasma concentration-time curve for BI 425809 from time 0 through the last data point at which the concentration remained quantifiable. The unit is hour*nanomol/liter. In general, an area-under-the-curve measure combines concentration and time into a summary of plasma exposure across the measured interval. It is useful in pharmacokinetic comparisons because it reflects the concentration profile over time rather than a single measurement at one sampling time.

The registry describes blood sampling from within 2 hours before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 47, 71, 119, 167, and 215 hours after BI 425809 administration. AUC0-tz uses the interval ending at the last quantifiable data point, so it is distinct from the listed secondary endpoint AUC0-∞, which extends the exposure measure to infinity through estimation.

The reported summaries are geometric least-squares means, described as adjusted geometric means, with adjusted geometric standard errors. In general, geometric summaries are commonly used for positive pharmacokinetic measures whose distributions may be asymmetric. The endpoint provides a standardized way to compare exposure under the fed and fasted conditions; it does not by itself measure a health benefit, harm, or clinical response.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes an analysis of variance (ANOVA) for the primary pharmacokinetic endpoint. The specified sources of variation are sequence, subjects within sequences, period, and treatment. The analysis treats subjects within sequences as random and the other listed effects as fixed. In general, ANOVA represents an outcome through a model that separates variation associated with specified design factors. In this crossover setting, treatment is the contrast of interest, while sequence and period account for other features of the design.

Why account for sequence and period?

Sequence identifies the order in which participants received the two conditions. Period identifies which treatment period contributed the measurement. Including these terms distinguishes the treatment comparison from possible differences associated with order or period. The record does not report a separate test of carryover, a washout interval, or a more detailed model specification. Those details should not be inferred from the fact that the study is a crossover trial.

Subjects within sequences are treated as a random effect in the described model. In general, a random effect allows the analysis to represent participant-level variability rather than treating each participant as an unrelated fixed category. This is relevant in a crossover design because measurements from the same participant are connected. The registry does not report the covariance structure, estimation procedure, model diagnostics, or how any departures from model assumptions were handled.

What do the geometric summaries represent?

The primary endpoint is summarized using geometric least-squares means, also described as adjusted geometric means. In general, a geometric mean summarizes positive values on a multiplicative scale and is often suitable when pharmacokinetic measurements are right-skewed. A least-squares mean is a model-adjusted summary, rather than a simple unadjusted mean of all observed values. Here, the registry’s description says the adjusted summaries were calculated using the stated ANOVA model.

The reported adjusted geometric mean ratio compares the test condition with the reference condition. In general, ratios make a relative comparison between two positive quantities. The registry reports the ratio as a percentage and gives a 90% confidence interval. The interval describes uncertainty around the estimated ratio under the model and its assumptions; it is not a range containing a known proportion of individual participants’ values. No p-value is reported for the treatment comparison, and the record does not identify an inferential decision rule or a target range for the ratio.

Why report a confidence interval?

In general, a confidence interval conveys both the estimate and its statistical uncertainty. A point estimate alone does not show how precisely the effect has been estimated. The limits of the interval indicate the uncertainty associated with repeated use of the stated estimation procedure, subject to its assumptions. The 90% interval in the registry is specific to the reported adjusted ratio. It should not be treated as a probability statement that the true value has a 90% chance of lying between the displayed limits after the data have been observed.

The registry lists adjusted geometric standard errors for the outcome description, but the arm-level posted summaries in the record do not include separate standard-error values. The treatment comparison is reported with its ratio and confidence interval. Additional details on standard-error calculation are not reported in the registry record.

What does the crossover design contribute?

In general, crossover designs allow each participant to contribute information under more than one treatment condition. This can reduce the influence of stable between-participant differences on a within-participant contrast. It does not eliminate all sources of uncertainty: period effects, sequence effects, missing observations, and model assumptions remain relevant. The analysis description identifies sequence, period, treatment, and subjects within sequences, but the registry does not report a detailed account of how incomplete sequences or protocol deviations affected the primary analysis.

The endpoint population is described as participants treated with at least one dose and providing at least one primary or secondary pharmacokinetic endpoint, unless an endpoint was excluded because of a relevant protocol deviation or was not pharmacokinetically evaluable. The remaining text of that population definition is not reported in the registry record. It is therefore not possible to reconstruct every inclusion or exclusion decision from the posted description.

Planning illustrations are not observed power

In general, a sample-size calculation depends on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. The record’s planning-illustration assumptions specify a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of the observed effect. Such calculations are planning illustrations based on the observed effect, not the trial’s own design rationale and not observed power. The registry does not report the trial’s sample-size justification or the numerical planning results in the registry record for this explanation. No conclusion about the study’s original power target should be drawn from those illustrations.

10. Analyses Reported by the Sponsor

The registry’s posted comparison gives the sponsor’s adjusted geometric mean ratio for BI 425809 with food relative to without food as 114.61%, with a 90% confidence interval from 110.13% to 119.27%. It is the stated adjusted comparison from the crossover analysis, which accounts for sequence, participants within sequences, period, and treatment.

No discrepancy is flagged between the sponsor’s reported analysis and the posted summary statistics. Accordingly, there is no reported conflict that would require a recalculated result to take precedence; if a discrepancy were identified, the sponsor’s own analysis would take precedence. The registry does not provide a p-value for this comparison, so one should not be inferred from the ratio or interval.

Any simple recalculation from the posted arm summaries would be unadjusted and would not reproduce the stated model-adjusted analysis. The posted adjusted ratio is therefore the appropriate figure to quote when describing the sponsor’s analysis. It should not be replaced by a separately derived comparison, nor should it be interpreted as a clinical outcome. The registry does not report the sponsor’s decision criteria for evaluating this ratio.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses overall. It identifies AUC0-tz as the primary outcome and AUC0-∞ as a secondary outcome. One secondary outcome is posted by name. The remaining outcome details are not reported in the registry record, so the full set of endpoints and analyses cannot be reconstructed from the information.

The registry record does not report a multiplicity adjustment or a plan for controlling the chance of false-positive findings across multiple endpoints or analyses. In general, when several hypotheses are examined, the interpretation of individual confidence intervals or tests can depend on whether and how multiplicity was addressed. The posted primary comparison is described with a 90% confidence interval, but no broader testing hierarchy or adjustment procedure is stated. It would be inappropriate to infer one.

The primary endpoint population is described as treated participants who provided at least one eligible pharmacokinetic endpoint, with exclusions for relevant protocol deviations or pharmacokinetic non-evaluability. The complete population definition is not reported in the registry record. The arm-level primary endpoint summaries each include 15 participants, while enrollment is reported as 16. The record does not explain the difference, identify which participant or periods were absent from the analysis, or give reasons for any missing measurements.

Missing-data handling is not described in sufficient detail to determine whether values were omitted, imputed, or handled by another method. In general, missing pharmacokinetic measurements can affect an endpoint if they prevent reliable estimation of the concentration-time profile. The registry does not report the extent or pattern of missing data, the handling of incomplete treatment periods, or sensitivity analyses. It also does not provide a protocol-deviation listing or a comparison of included and excluded participants.

These gaps limit assessment of how the analysis population was formed and how robust the estimate is to incomplete data or multiple analyses. They do not alter the reported ratio, but they constrain what can be concluded about the analysis process beyond the stated model and endpoint population description.

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 adverse-event figures distinguish serious adverse events from other adverse events and present counts for the two treatment conditions. For BI 425809 without food, 16 participants were at risk for serious adverse events and 0 had a serious adverse event; 16 were at risk for other adverse events and 6 had one. For BI 425809 with food, 15 participants were at risk for serious adverse events and 0 had a serious adverse event; 15 were at risk for other adverse events and 5 had one. The record reports 0 deaths in both conditions.

These are counts in a small trial, not evidence that an event could never occur. The record does not provide the event terms for the other adverse events, their severity, duration, relatedness, or whether participants experienced more than one event. The list of top serious-event terms is empty, consistent with the posted count of no serious events, but it does not add detail about other events.

Because this was a crossover study, participants could contribute safety information under both conditions; the at-risk counts differ between the conditions. The record does not explain the count difference. These figures should be read as descriptive safety reporting for this study, not as a definitive comparison of risk between conditions or a basis for conclusions about safety in other populations or settings.

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

The result describes a pharmacokinetic comparison of BI 425809 taken with food and without food in healthy participants. The primary measure is plasma exposure from time 0 to the last quantifiable concentration. The registry’s adjusted geometric mean ratio is 114.61%, with a 90% confidence interval from 110.13% to 119.27%. The ratio is reported for the with-food condition relative to the without-food condition, and the endpoint summaries are 4026.0 and 4614.0 hour*nanomol/liter, respectively.

These statistics convey the estimated relative exposure and its precision under the stated analysis. They do not describe how an individual participant’s concentration changed, nor do they establish a clinical consequence of the exposure comparison. The record does not report a decision threshold for the ratio, a p-value, or a clinical outcome tied to the endpoint. No claim about efficacy or treatment benefit follows from these pharmacokinetic results.

The trial enrolled 16 healthy participants, and the primary endpoint summaries include 15 participants in each condition. The record does not explain the analysis-count difference or give enough information to evaluate all missing-data decisions. Its findings are specific to the described single-dose conditions and the trial’s population. The registry does not establish whether the same comparison applies to repeated dosing, people with a health condition, or other clinical circumstances.

The crossover design and model are relevant to interpretation: treatment, period, sequence, and subjects within sequences were included in the stated ANOVA. That adjustment supports the reported comparison under the model assumptions, but does not remove uncertainty or supply information that the record does not report, such as diagnostic checks and sensitivity analyses. The result is best understood as a model-based estimate of relative plasma exposure in this completed Phase 1 study, with the stated confidence interval and limitations.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of a randomized crossover design applied to a pharmacokinetic question. Rather than comparing separate groups assigned to only one condition, the design used two treatment sequences so that the fed and fasted conditions could be evaluated across periods. In general, this structure can make within-participant comparisons useful when stable differences between participants contribute substantially to outcome variability.

The analysis description also shows why the design and model need to be read together. Sequence, period, treatment, and subjects within sequences are named as sources of variation, and the participant effect is treated as random. The posted treatment comparison is an adjusted geometric mean ratio, not simply a contrast between two raw averages. The ratio and its confidence interval communicate the estimated relative exposure and uncertainty in that adjusted comparison.

The record also illustrates the limits of registry summaries. Although the primary endpoint population is described, the full definition is incomplete; the enrollment count differs from the endpoint-summary counts, with no reason reported; and details of missing-data handling and multiplicity are not reported. These omissions matter for understanding how the reported estimate was formed and how broadly it can be interpreted.

Finally, this is a pharmacokinetic study in healthy participants, not a clinical-outcome trial. Its statistical contribution is a focused comparison of exposure under two dosing conditions, not a conclusion about clinical effects. Keeping that distinction clear is essential when translating a numerical result into a scientific interpretation.

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 trial is small, with 16 participants enrolled and 15 included in each posted arm-level primary endpoint summary. The registry does not explain the difference between enrollment and those endpoint counts, identify missing periods, or describe how incomplete pharmacokinetic profiles were handled. This limits assessment of possible selection or missing-data effects.

The population is described as healthy subjects. The result therefore pertains to the stated study population and conditions; the record does not establish applicability to people with a health condition or to other treatment settings. The trial is described as involving single-dose administration, so conclusions about repeated dosing are not reported.

The primary endpoint analysis is described as an ANOVA that accounts for sequence, subjects within sequences, period, and treatment. The registry does not report model diagnostics, distributional checks, the covariance structure, or sensitivity analyses. It also does not report a washout interval or a detailed assessment of carryover. These omissions prevent a fuller independent assessment of the model and crossover assumptions.

The posted treatment comparison has a 90% confidence interval, and no p-value or decision threshold is reported. The registry does not state a multiplicity procedure, a detailed sample-size justification, or the full analysis plan. It lists three outcome measures and three analyses but provides limited detail about the full set. Safety reporting gives counts for serious and other adverse events but not the terms, severity, duration, or relatedness of the other events. Together, these limitations restrict interpretation to the reported pharmacokinetic comparison and descriptive safety counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study in Healthy People to Test How BI 425809 is Taken up in the Body When Taken With or Without Food — NCT05347004.
• Registry record last updated 2026-04-20; status last verified 2026-04.
• Results first posted 2026-04-20.
• 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

NCT05347004 is a completed Phase 1 randomized, open-label, two-period, two-sequence crossover trial sponsored by Boehringer Ingelheim. It enrolled 16 healthy participants and compared a single dose of BI 425809 taken with food against a single dose taken without food.

The primary endpoint was AUC0-tz, plasma exposure from time 0 to the last quantifiable data point. The registry reports adjusted geometric least-squares means of 4026.0 hour*nanomol/liter without food and 4614.0 hour*nanomol/liter with food, with 15 participants in each summary. The adjusted geometric mean ratio for with food relative to without food was 114.61%, with a 90% confidence interval from 110.13% to 119.27%.

The analysis description names an ANOVA accounting for sequence, subjects within sequences, period, and treatment. The record also reports 0 serious adverse events in each condition. Missing-data details, the full analysis plan, and reasons for the difference between enrollment and endpoint-summary counts are not reported in the registry record.