A Study in Healthy Men to Test How Zongertinib (BI 1810631) is Taken up and Processed by the Body: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in Healthy Men to Test How Zongertinib (BI 1810631) is Taken up and Processed by the Body (NCT05879991), a non-randomized phase 1 study. The primary outcome is Part A - Fraction Excreted in Urine and Faeces as Percentage of the Administered Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe0-tz).

2. Clinical Question

The central Part A question is about drug disposition and recovery, rather than a clinical treatment effect. Radioactivity measurements track zongertinib-related material, including the drug and its radioactive metabolites. The registry record describes the collection schedule and endpoint definition, but the observed recovery values are not reported in the registry record.

Part A also assessed plasma concentrations of zongertinib and total radioactivity. Part B examined dose-normalized plasma concentration measures as secondary outcomes. Those objectives characterize how the compound and related material appear in blood; they do not by themselves establish a clinical benefit or harm. Results for those outcomes are not reported in the registry record.

3. Trial Design

This was a phase I, open-label trial conducted in two parallel parts. The allocation was non-randomized, and masking was not used. The registry record lists an enrollment of 15 and a completed study. The recorded study dates are 2023-08-10 for the start and 2023-10-19 for primary completion.

Part A focused on mass balance after a single oral dose of radioactive zongertinib solution. Participants took the solution with 240 mL of water after an overnight fast of at least 10 h. The main objective was to assess recovery of radioactivity in urine and faeces. Plasma concentrations of zongertinib and radioactive material were secondary objectives.

Part B focused on absolute bioavailability. Participants took one film-coated tablet orally with 240 mL of water after an overnight fast of at least 10 h. Two hours later, they received a single solution of radioactive zongertinib as an intravenous microtracer reference treatment. This sequence is the basis for the Part B objective; it is not a randomized comparison of independent treatment groups.

The registry record describes the two parts as parallel, but does not report the detailed assignment process or participant flow between parts. It also does not report whether any participants discontinued or were excluded from particular analyses. The safety groups listed in the registry record include 8 participants in Part A and 7 in Part B. These group-specific safety counts do not supply a full account of enrollment, completion, or analysis exclusions.

Because this was an open-label, non-randomized pharmacokinetic study in healthy volunteers, its design is suited to describing drug disposition under the specified dosing and sampling conditions. It does not provide a randomized estimate of a clinical outcome against a control treatment. The protocol's detailed statistical plan, sample-size justification, and any interim analyses 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 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) parameter analysis set (PKS) restricted to Part A included all part A subjects in the TS who provided 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.

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

6. Primary Endpoint

The registry lists the primary outcome as Part A - Fraction Excreted in Urine and Faeces as Percentage of the Administered Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe0-tz), measured over Within 18 h (urine) or 48 h (faeces) before drug intake; at 0-4, 4-8, 8-12, 12-24 (urine); and at 24 h sampling intervals until 336 h after drug intake (both). Both: after 336 h, every 7 days, up to day 42. Continues in description..

The Part A primary endpoint is the fraction of the administered oral dose recovered in urine and faeces as a percentage of the dose, measured from dosing through the last quantifiable time point. The registry record describes separate urine and faeces fractions based on radioactivity assessed as zongertinib-equivalent material. The endpoint is reported using a geometric mean and geometric coefficient of variation.

Mass-balance assessments are used to describe how much administered radioactive material is recovered through the measured routes and over the specified collection period. This helps characterize disposition and recovery of drug-related material. It does not, on its own, identify the amount of unchanged parent drug absorbed, establish the activity of metabolites, or demonstrate a clinical effect.

Urine was collected before dosing and at specified intervals after dosing. Faeces collection was scheduled at 24 h intervals after dosing. After 336 h, additional 24 h collections could be performed every 7 days on days 21, 28, 35, and 42 if warranted. Collection stopped when release criteria for radioactivity recovery were met, with stopping possible as early as Day 15. The registry record also describes an initial collection schedule and notes that the timing information continues in the endpoint description.

The observed geometric mean, its geometric coefficient of variation, and the number of participants contributing to the primary endpoint are not reported in the registry record. Therefore, the extent of recovery and its precision cannot be assessed from the reported endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the Part A primary measure as a geometric mean with geometric coefficient of variation. It does not provide the numerical endpoint estimates, detailed model specification, transformations, confidence intervals, or hypothesis tests. The following statistical explanations are general; they clarify the measures named in the registry record but do not describe unreported analysis decisions.

What does a geometric mean describe?

General: A geometric mean summarizes positive measurements on a multiplicative scale. It is often useful for pharmacokinetic quantities, which can be right-skewed: a small number of comparatively large values may make an arithmetic mean less representative of a typical participant. Conceptually, the geometric mean is obtained by averaging log-transformed values and transforming the average back to the original scale. The registry record does not state the precise calculation procedure used for the endpoint.

A geometric mean is not interchangeable with an arithmetic mean. It summarizes the central tendency in a way that reflects multiplicative variation. Without the observed value and its uncertainty, however, naming the summary measure does not tell the reader where the study's results lie or how well the estimate is determined.

What does geometric coefficient of variation describe?

General: A coefficient of variation expresses dispersion relative to a central value. A geometric coefficient of variation is designed for data summarized geometrically and describes multiplicative spread on that scale. A larger value indicates more variability in the measured values relative to their geometric center. It is not a confidence interval and does not directly state how precisely the geometric mean has been estimated.

The registry record names this dispersion measure for the primary endpoint but does not report its value. It also does not provide a confidence interval for the geometric mean. The precision of the primary endpoint therefore cannot be assessed from the endpoint specification alone.

Why measure radioactivity in urine and faeces?

General: After administration of a radiolabelled compound, measurement of radioactivity in collected excreta can support a mass-balance assessment. It tracks drug-related radioactive material, which may include parent compound and metabolites. The amount recovered is interpreted in relation to the administered dose and collection period. It is not automatically a direct measure of unchanged drug, absorption, or pharmacological activity.

Collection duration and completeness are relevant because material still present in the body or excreted after collection ends will not be captured in the measured total. The registry record describes scheduled collections and stopping conditions, including possible additional collections after 336 h and stopping when radioactivity-recovery release criteria were met. The actual collection duration and observed recovery for participants are not reported in the registry record.

How does the Part B objective differ?

General: Absolute bioavailability concerns the proportion of a dose reaching systemic circulation after administration by a particular route, compared with intravenous administration. An intravenous reference is used because it enters the circulation directly. In this study, the registry record describes an oral film-coated tablet followed two hours later by an intravenous microtracer dose. Dose-normalized plasma exposure measures are listed as secondary outcomes. The detailed calculation method and any resulting bioavailability estimate are not reported in the registry record.

Maximum measured concentration and area under the concentration-time curve address different aspects of plasma exposure. The maximum concentration describes the highest measured concentration during the sampling period. The area under the curve summarizes concentration over time through the last quantifiable time point. Dose normalization expresses these measures in relation to the administered dose, supporting comparison when doses differ. The registry record names these outcomes but does not report their values or the specific analysis procedures.

What can a planning illustration establish?

General: A sample-size planning illustration based on an observed effect is not observed power. It asks how many participants might be needed under stated assumptions to detect a chosen effect size. The registry record describes planning assumptions of a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. It also distinguishes total events for time-to-event calculations from participants per arm for other calculations.

These assumptions describe an illustration, not the original study's design justification. The registry record does not report the trial's own sample-size justification, and the observed endpoint estimates needed to understand any such illustration are not reported in the registry record. A planning calculation cannot substitute for the study's observed results or their uncertainty.

More broadly, the registry record does not report the detailed statistical analysis plan, model choices, handling of values below quantification limits, confidence-interval procedures, or interim analyses. Those details should not be inferred from the named summary measures or objectives.

10. Multiplicity, Missing Data and Analysis Populations

The study has multiple objectives and outcomes across its two parts. Part A's primary objective concerns mass balance and total recovery of radioactivity, while plasma concentration measures are secondary. Part B's primary objective concerns absolute bioavailability, and its listed secondary outcomes include dose-normalized maximum concentration and area under the concentration-time curve. The registry record lists 8 outcome measures and 3 analyses, but does not report their detailed statistical specifications.

When several outcomes are tested, multiplicity can increase the chance of at least one nominally positive finding if each is assessed separately. Statistical plans may address this through a testing hierarchy, adjusted significance thresholds, or other approaches. The registry record does not report whether multiplicity was controlled, how outcomes were prioritized for inference, or whether any confirmatory hypothesis tests were planned. No adjustment method should be assumed.

The Part A primary endpoint population is described as a restricted pharmacokinetic parameter analysis set. It includes Part A participants in the treatment set who provided at least one primary or secondary pharmacokinetic endpoint and were not excluded because of a relevant protocol deviation or pharmacokinetic non-evaluability. The number of participants meeting this definition is not reported in the registry record. The record also does not report the corresponding analysis population definitions for every other outcome.

Missing-data methods are not reported in the registry record. The record does not specify how incomplete urine or faeces collections, missing samples, values below quantification limits, or other non-evaluable measurements were handled. It also does not report the extent of missingness or the reasons for any exclusions. These gaps limit assessment of how the analyzed participants and measurements relate to all enrolled participants and scheduled observations.

The study's non-randomized structure and its distinct Part A and Part B objectives also mean that results should not be interpreted as a single randomized treatment comparison. Detailed inferential procedures, including any handling of multiple comparisons, are not reported in the registry record.

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 posted safety figures list serious adverse events, other adverse events, and deaths separately for the two treatment groups. In Part A, no serious adverse events were reported among 8 participants at risk; 7 participants were affected by other adverse events, and deaths were 0. In Part B, no serious adverse events were reported among 7 participants at risk; 2 participants were affected by other adverse events, and deaths were 0.

These are participant counts, not event counts. The figures indicate how many participants in each safety group were affected within the listed categories; they do not show how many separate events each participant experienced. No serious adverse-event terms are listed in the registry record.

The figures do not establish whether events were caused by treatment, and they do not support a randomized comparison of safety between groups. The study was non-randomized, open-label, and organized around different pharmacokinetic objectives in Part A and Part B. The registry record does not provide event descriptions, severity details for the other adverse events, or further information about attribution. The counts should therefore be read as a limited descriptive account of the posted safety groups, not as a comparative estimate of risk.

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

The study was designed to characterize how zongertinib and radioactive drug-related material are handled by the body in healthy male volunteers. Part A measured radioactivity recovered in urine and faeces after an oral solution dose. Part B investigated absolute bioavailability using an oral tablet and an intravenous microtracer reference. These are pharmacokinetic questions about exposure, disposition, and recovery.

The registry record does not report the numerical primary endpoint result, the Part B bioavailability estimate, or the listed plasma concentration outcomes. Consequently, readers cannot determine the magnitude of recovery or bioavailability, the variability of these estimates, or their statistical precision from the information reported. A stated objective is not evidence that the objective was met in a particular way.

Even if numerical pharmacokinetic results were available, they would describe measurements under the study's dosing and collection conditions. They would not, by themselves, establish a clinical benefit, lack of benefit, or clinical safety in a patient population. Participants were healthy male volunteers, and the study was a phase I investigation rather than a randomized clinical-outcome comparison.

The safety counts provide a limited descriptive account: no serious adverse events or deaths were listed in either group, while other adverse events were recorded for participants in both groups. These counts do not establish causality or permit a reliable treatment comparison. The registry record's non-randomized design further limits such comparisons.

The appropriate interpretation is therefore bounded by the information recorded: the study objectives, treatment sequence, collection procedures, endpoint definitions, analysis population description, and safety counts are available, while the principal pharmacokinetic estimates and many statistical details are not reported in the registry record. Neither the absent results nor the design should be used to infer an unreported conclusion.

13. Why This Trial Matters Statistically

Pharmacokinetic studies answer questions that are distinct from whether a treatment changes a clinical outcome. A mass-balance assessment tracks recovery of radioactive drug-related material, while an absolute-bioavailability assessment compares exposure after oral dosing with an intravenous reference. Distinguishing these aims helps readers understand what a study can establish and what lies outside its scope.

This study also illustrates why an endpoint definition is not a result. The registry record describes the radioactivity collection schedule, the geometric summary measures, and the Part A analysis population, but it does not report the observed endpoint estimates. Without those estimates and their uncertainty, the central quantitative question remains unanswered in the registry record.

The design matters statistically as well. The trial was open-label and non-randomized, with separate objectives across two parts. Part B's oral and intravenous treatments were administered in a specified sequence. These features should shape interpretation of any comparison and discourage treating the groups as randomized, interchangeable arms. The record itself notes that the arms are not a like-for-like control comparison.

Finally, the listed safety counts show why denominators and outcome categories need to be kept clear. Serious adverse events, other adverse events, and deaths are distinct categories, and the counts are participants affected rather than a complete description of each event. Without event details or randomized allocation, the counts are descriptive rather than comparative evidence.

Reading the registry record this way separates the study's scientific purpose from conclusions that require unreported numerical results. It also makes clear which questions concern drug disposition and which would require evidence from other kinds of clinical research.

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 consequential limitation for interpretation is that the registry record does not report the numerical primary endpoint results. It also does not report the Part B bioavailability estimate or the values for the listed plasma pharmacokinetic outcomes. The size, variability, and precision of the observed pharmacokinetic measurements therefore cannot be assessed from the registry record.

The study was non-randomized and open-label, and the two parts addressed different objectives. Part A was a mass-balance assessment; Part B used an oral tablet followed by an intravenous microtracer. The registry record cautions that the arms are not a like-for-like control comparison. This design does not support treating the groups as randomized controls for comparative conclusions.

The study population was healthy male volunteers. The registry record does not establish how the measurements generalize beyond that population. The listed enrollment was 15, and the safety groups included 8 participants in Part A and 7 in Part B. The registry record does not provide a detailed participant-flow account or state how many participants contributed to each endpoint.

For the primary endpoint, recovery depends on collected samples and the observation period. Although the registry record describes collection schedules and stopping criteria, it does not report actual collection durations, completeness, missing samples, or handling of non-evaluable measurements. The missing-data procedures and detailed statistical plan are not reported in the registry record.

The registry record also does not report the study's sample-size justification, interim analyses, multiplicity handling, or full inferential procedures. The planning assumptions described for an illustration should not be mistaken for the trial's own design rationale. These limitations leave important questions about analysis conduct and precision unresolved.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study in Healthy Men to Test How Zongertinib (BI 1810631) is Taken up and Processed by the Body — NCT05879991.
• Registry record last updated 2025-10-06; status last verified 2025-09.
• Results first posted 2025-09-22.
• 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

The registry record describes NCT05879991, a completed phase I, open-label, non-randomized study in healthy male volunteers, with 15 participants enrolled. It had two parallel parts: Part A assessed mass balance after a single oral dose of radioactive zongertinib solution, and Part B investigated absolute bioavailability after an oral tablet followed by an intravenous radioactive microtracer.

The Part A primary endpoint was the fraction of the administered dose recovered in urine and faeces through the last quantifiable time point, summarized using a geometric mean and geometric coefficient of variation. The registry record describes the sampling schedule and the Part A pharmacokinetic analysis population. It does not report the primary endpoint estimates or the Part B bioavailability result.

The posted safety groups list no serious adverse events and no deaths in either part. Other adverse events affected 7 participants in Part A and 2 in Part B. Because allocation was non-randomized and the two parts had different objectives, these groups are not a like-for-like control comparison.