A Study in Healthy Men to Measure the Amount of BI 425809 in the Blood When Taken as a Tablet: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in Healthy Men to Measure the Amount of BI 425809 in the Blood When Taken as a Tablet (NCT03783000), a na phase 1 study. The primary outcome is Area Under the Concentration-time Curve of the Analyte ([14C]-BI 425809 After iv Administration as Well as for BI 425809 After Oral Administration) Over the Time Interval From 0 to Infinity (AUC0-∞, Norm).

2. Clinical Question

This is a pharmacokinetic question about the extent of systemic exposure following two routes of administration, not a comparison of clinical benefit between treatment groups. The oral tablet is identified as the test treatment and the intravenous microtracer as the reference. Because both were administered within the single-group study, the design is not a randomized, parallel-group comparison. The record does not report a placebo group, a disease population, or a clinical efficacy endpoint. Its focus is the concentration-time behavior of the analyte and the comparison of exposure after oral and intravenous administration.

3. Trial Design

This completed Phase 1 study investigated pharmacokinetics and absolute oral bioavailability in healthy male volunteers. The registry record gives a start date of 2019-01-15 and a primary completion date of 2019-03-06. Enrollment was 6. The study is described as a single-group study, with no masking and allocation listed as not applicable. Those design details matter: this was not a randomized comparison of separate groups, and the intravenous reference should not be read as an independent control arm.

The arm description says participants received a single oral 25 milligram dose of BI 425809 in a film-coated tablet and an intravenous microtracer infusion of 30 microgram [C-14]-BI 425809. The record identifies the tablet as test treatment T and the intravenous tracer as reference treatment R. The registered primary objective was to investigate absolute oral bioavailability by comparing the pharmacokinetic exposure measures associated with these routes.

For treatment T, pharmacokinetic samples were collected before dosing and at post-dose times extending to 168 h. The record specifies scheduled collections at 1, 2, 3, 4.083, 6, 8, 12, 24, 72, 120 and 168 h after oral administration. It also gives a schedule for treatment R, with collection times at 3, 4.083, 4.167, 4.25, 4.5, 5, 6, 7, 8, 12, 16, 24, 72, 120 and 168 h after oral administration. These scheduled measurements support estimation of concentration-time exposure. The record does not describe the detailed infusion timing beyond identifying it as an intravenous microtracer infusion.

The registry lists a secondary outcome for maximum measured plasma concentration after a single oral dose and reports 2 outcome measures and 1 analysis. Further details about allocation procedures, protocol deviations beyond the endpoint population definition, and the rationale for the enrollment 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 participants were screened for eligibility to participate in the trial. Participants attended specialist site which would then ensured that all participants met all inclusion/exclusion criteria. Participants were not to be administered to trial treatment if any one of the specific entry criteria were not met.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) set (PKS): All participants in the treated set (TS) who provided at least one primary or secondary PK endpoint not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.

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): All participants who were randomized and received at least one dose of the trial medication.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Concentration-time Curve of the Analyte ([14C]-BI 425809 After iv Administration as Well as for BI 425809 After Oral Administration) Over the Time Interval From 0 to Infinity (AUC0-∞, Norm), measured over Pharmacokinetic samples were collected within 2 h before and up to 168 h after single oral administration of unlabelled BI 425809. Further details are in description..

The primary endpoint is the dose-normalised area under the concentration-time curve from time zero to infinity, designated AUC0-∞, norm. It is defined for [14C]-BI 425809 after intravenous administration and BI 425809 after oral administration. Area under the curve represents total measured drug-related exposure across the sampled concentration-time profile, with the endpoint extending the profile to infinity. Dose normalisation puts exposure on a per-dose basis, allowing the oral and intravenous measures to be compared despite the different administered amounts.

Absolute oral bioavailability concerns the extent to which an orally administered drug reaches systemic circulation relative to intravenous administration. In general, a dose-normalised exposure comparison between oral and intravenous routes can inform that question because an intravenous dose enters systemic circulation directly, whereas an oral dose must be absorbed. This is a general pharmacokinetic interpretation; it does not establish the result of this trial.

The record says that adjusted geometric least squares means and adjusted geometric standard errors were calculated from an analysis of variance on the logarithmic scale. It does not report the actual means, standard errors, treatment comparison, confidence interval, or numerical bioavailability estimate. Consequently, the endpoint definition and planned modeling approach can be described, but the magnitude and precision of the observed primary result are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes an endpoint based on the area under a concentration-time curve. General explanation: concentrations measured after dosing are considered together over time to represent exposure, rather than relying on a single concentration measurement. AUC0-∞ extends that exposure concept from time zero through the period after the last measured concentration, with the tail of the curve represented through infinity. The record does not provide the endpoint values or details about how the terminal portion of the curve was estimated.

Why use dose-normalised exposure?

The oral tablet and intravenous microtracer were administered in different amounts. In general, dividing exposure conceptually by dose supports comparison of exposure per unit dose, which is useful when the scientific question concerns absolute bioavailability across administration routes. The registered endpoint is explicitly dose-normalised. No numerical dose-normalised estimates or calculated bioavailability value are reported in the registry record, so no such value can be inferred from the endpoint name alone.

Why analyze the logarithmic scale?

The registry states that the analysis of variance model was performed on the logarithmic scale. General explanation: pharmacokinetic measures such as exposure are often positive and can vary proportionally, so analysis on a log scale can make multiplicative differences more suitable for a linear-model framework. A difference on the log scale corresponds to a ratio after transforming back to the original scale. This description explains the general statistical rationale; it does not establish the particular ratio or its uncertainty in this study.

What do geometric least squares means represent?

The primary endpoint is summarized using adjusted geometric least squares means. General explanation: a geometric mean is obtained by working with logarithms and transforming the average back to the original scale. The “least squares” terminology refers to model-based adjusted estimates, rather than necessarily being a simple summary of raw observations. Here, the registry says formulation was a fixed effect and subject was a random effect. The estimates are adjusted according to that model structure. Their numerical values are not reported in the registry record.

Why include subject as a random effect?

Because the design describes the oral test treatment and intravenous reference treatment within one group, measurements from the same participant may be related. In general, a model that accounts for participant-level variation can distinguish differences associated with formulation from baseline variation between participants. A random subject effect represents participant-to-participant variation in the model. This is a general explanation of the stated model term, not a claim about the size of within-participant correlation or the fit of the model in this study.

What is a standard error?

The endpoint description identifies an adjusted geometric standard error. General explanation: a standard error describes the statistical uncertainty of an estimated quantity under a specified model and sampling process. It is not the same as the range of individual participant values. A standard error can contribute to inference about an estimate, but it does not by itself communicate the full range of plausible treatment effects as a confidence interval would. The registry record does not report the numerical standard errors or a confidence interval for the primary endpoint.

How do the sampling times support the endpoint?

The protocol description lists collection schedules after the single oral administration for test treatment T and reference treatment R, with the final listed scheduled time at 168 h. Repeated sampling helps characterize the concentration-time profile, including its early and later portions. In general, a denser schedule around changing concentrations can help describe the profile, while later observations can inform its terminal behavior. The record lists the scheduled times, but does not report participant-level sampling completeness, measured concentrations, or the degree to which any estimated AUC depended on extrapolation.

What can a planning illustration say?

General explanation: a sample-size calculation can illustrate how many participants per arm might be needed under chosen assumptions for a future comparison. Such a calculation depends on the effect targeted, variability, allocation, significance level, and statistical approximation. The registry’s planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The record cautions that these illustrations are not the trial’s own design. In particular, they do not represent observed power, and a hypothetical two-arm planning framework should not be mistaken for this single-group pharmacokinetic design.

The record does not report the numerical inputs or results of any sample-size illustrations in the registry entries, nor does it report an original sample-size justification. A planning illustration is conditional on its assumptions and is not a substitute for the trial’s observed endpoint estimate, uncertainty interval, or analysis plan. No conclusion about the adequacy of enrollment can be drawn from the planning description alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary pharmacokinetic endpoint and a secondary outcome for maximum measured plasma concentration after a single oral dose. It also reports 2 outcome measures and 1 analysis. The primary endpoint is dose-normalised AUC0-∞, while the secondary outcome concerns Cmax. The numerical results for these endpoints are not reported in the registry record.

Multiplicity refers generally to the statistical issue that can arise when several outcomes or comparisons are tested: the chance of a false-positive finding can increase when many inferences are considered together. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a plan for controlling a family-wise error rate. It also does not report whether the secondary outcome was intended as confirmatory or descriptive. No particular adjustment or testing strategy should be inferred.

The primary endpoint population is defined as the pharmacokinetic set: participants in the treated set with at least one primary or secondary pharmacokinetic endpoint not excluded because of a relevant protocol violation or pharmacokinetic non-evaluability. This definition makes clear that the analysis population need not be identical to everyone enrolled. The registry entries do not state how many participants met the pharmacokinetic-set criteria, how many observations were excluded, or the reasons for any exclusions in this trial.

Missing-data procedures, rules for handling incomplete concentration profiles, and sensitivity analyses are not reported in the registry record. Nor is there detail on whether missing values were imputed or how any non-evaluable pharmacokinetic measurements were handled beyond the population definition. These omissions limit assessment of how missing or excluded observations may have affected the endpoint estimates. The registered population definition and endpoint model can be described, but they do not reveal the completeness of the analysis data or the robustness of results to alternative handling choices.

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 registry’s safety summary lists 0 serious adverse events among 6 participants at risk. It separately lists 3 participants with other adverse events among 6 at risk. These are aggregate counts for the single group receiving the oral BI 425809 treatment and intravenous [C-14]-BI 425809 microtracer. The categories should be kept separate: the serious-event count is not the same measure as the count for other adverse events.

The record does not provide the specific terms for the other adverse events in the information, and no top serious-event terms are listed. The summary therefore does not show which events occurred, their timing, duration, severity apart from the serious/non-serious categorization, or whether any particular event was judged related to a treatment. The registry record also does not provide further detail about the basis of event attribution.

These counts are descriptive and should be interpreted in the context of a completed Phase 1 pharmacokinetic study in healthy male volunteers. They do not determine the overall safety profile of BI 425809, and the absence of listed serious events in this record is not proof that serious events cannot occur. The safety figures do not answer the primary question about dose-normalised exposure or absolute oral bioavailability.

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

The registered study asks a pharmacokinetic question: how dose-normalised exposure after oral BI 425809 compares with exposure after an intravenous [C-14]-BI 425809 microtracer. The trial enrolled healthy male volunteers, used a single-group design, and defines a primary endpoint based on AUC0-∞, norm. The analysis description specifies a log-scale analysis of variance model with formulation as a fixed effect and subject as a random effect.

Those details explain what the study was designed to measure and how the primary endpoint was modeled. They do not provide the observed answer. The numerical endpoint estimates, uncertainty measures, comparison, and bioavailability result are not reported in the registry record. Consequently, the record does not support a numerical statement about the extent of oral bioavailability, the size of any exposure difference, or the precision of that difference.

The study is not a randomized parallel-group trial and does not compare clinical outcomes between separate treatment arms. The oral tablet and intravenous microtracer serve different roles in a route-based pharmacokinetic assessment. The results, if available, would concern exposure under the study conditions rather than demonstrating clinical benefit or establishing effects in a patient population. No medical conclusion should be drawn from the endpoint definition or the fact that the study is marked completed.

The registry’s safety summary records 0 serious adverse events and 3 participants with other adverse events, each among 6 at risk. These figures are limited aggregate descriptions. The available record does not give the event terms for the other adverse events or enough detail to characterize event patterns.

In short, this record identifies the population, treatments, pharmacokinetic endpoint, analysis model, and a limited safety summary. It does not report the primary numerical result or its uncertainty. That distinction is central: study objectives and methods establish the question and planned approach, while outcome estimates are needed to judge what the observed data indicate and how precisely they answer the question.

13. Why This Trial Matters Statistically

This study is statistically instructive because it uses a within-participant route comparison rather than separate randomized groups. Participants received the oral test treatment and an intravenous microtracer reference, and the primary endpoint compares dose-normalised exposure. In general, a within-participant approach can account for some differences between people because each participant contributes measurements under both conditions. The registry’s model reflects this structure by including subject as a random effect.

The study also illustrates why endpoint scale and model specification matter in pharmacokinetics. AUC summarizes a concentration-time profile, dose normalisation makes route-based exposure comparison possible in principle, and a log-scale model supports analysis of proportional differences. Adjusted geometric least squares means are model-based summaries, rather than automatically being interchangeable with raw arithmetic averages. Understanding those choices helps readers interpret what the planned analysis targets.

At the same time, a methods description is not a result. The registry record does not report the primary endpoint estimates or their uncertainty, so it cannot quantify bioavailability or show how precisely the study estimated the route comparison. This is a useful reminder to distinguish an outcome’s definition and analysis plan from the numerical evidence needed to interpret it.

The endpoint population definition and the limited safety counts also demonstrate the value of asking who contributed evaluable data and what an adverse-event summary actually counts. The record describes eligibility for the pharmacokinetic set, but does not report the size of that set. It reports aggregate adverse-event counts without the terms needed for a detailed event-level interpretation. Statistical reading therefore depends not only on models, but also on clear reporting of analysis populations, estimates, uncertainty, and outcome detail.

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 most important limitation for interpretation is that the registry record does not report the numerical primary endpoint result. It gives the endpoint definition and model description, but not the adjusted geometric least squares means, standard errors, a treatment comparison, a confidence interval, or a numerical bioavailability estimate. The magnitude and precision of the primary finding therefore cannot be assessed from this record.

The enrollment was 6, and the study population was healthy male volunteers. Findings from this population and study setting would not, by themselves, establish how exposure behaves in other populations or under other conditions. The record describes a single-group design and no masking; it is not a randomized comparison between separate groups. The intravenous microtracer functions as the reference treatment in the route assessment, but should not be mistaken for an independent control arm.

The record specifies sampling schedules, but does not report how complete the concentration profiles were, the number of participants included in the pharmacokinetic set, or the details of any endpoint exclusions. It does not explain the method used to estimate the portion of AUC extending to infinity or report sensitivity analyses. Missing-data procedures and the extent of any missing observations are not reported in the registry record.

The registry lists a secondary Cmax outcome, but its numerical result is not reported. A multiplicity strategy is also not reported in the registry record. The adverse-event summary gives aggregate counts but does not provide the terms for the other adverse events in the available record. Finally, although the registry includes planning assumptions for sample-size illustrations, the original sample-size justification and statistical plan are not reported. These gaps limit assessment of both result-level precision and analysis robustness.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study in Healthy Men to Measure the Amount of BI 425809 in the Blood When Taken as a Tablet — NCT03783000.
• Registry record last updated 2026-03-27; status last verified 2026-02.
• Results first posted 2026-03-27.
• 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

NCT03783000 is a completed Phase 1 study sponsored by Boehringer Ingelheim. It enrolled 6 healthy male volunteers and investigated pharmacokinetics and absolute oral bioavailability of BI 425809. Participants received a single oral 25 milligram tablet dose and an intravenous 30 microgram [C-14]-BI 425809 microtracer infusion.

The primary endpoint was dose-normalised AUC0-∞ for the oral and intravenous analytes. The record describes a log-scale analysis of variance model with formulation as a fixed effect and subject as a random effect. It lists a secondary Cmax outcome. Numerical primary and secondary results are not reported in the registry record.

The safety summary lists 0 serious adverse events and 3 participants with other adverse events, among 6 at risk. The record does not provide further event terms for the other adverse events in the available information.