A Study in Healthy Men to Test How BI 730357 is 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 BI 730357 is Processed by the Body (NCT03664011), a na phase 1 study. The primary outcome is Mass Balance Recovery of Total [14C]-Radioactivity in Urine (Feurine, 0-tz).

2. Clinical Question

3. Trial Design

This was a Phase I, open-label, single-dose, single-group study in healthy male volunteers. The registry lists an enrollment of 6 and records the study as completed. The intervention was an oral dose of 50 mg BI 730357 containing [C-14]-labelled and unlabelled drug substance. No separate control arm or randomized allocation is described, so the design is not a like-for-like comparison of treatments.

The stated objectives were to assess mass-balance recovery of BI 730357 radioactivity in urine and faeces after dosing and to obtain plasma, urine, and faecal samples for metabolite profiling and structural identification. The primary endpoint in the record concerns urinary recovery; it is not a measure of a clinical health outcome or a comparison of treatment effects.

Urine collection was scheduled across intervals beginning with a predose period and continuing through successive post-dose intervals. The schedule describes collection through 312–336 hours after dosing, continued in 24-hour intervals, and collection every 7 days from Day 21 until Day 50. The endpoint definition uses the latest quantifiable data point across participants to set the end of the cumulative interval.

The record lists maximum measured concentration and area under the concentration-time curve for 14C-BI 730357-equivalent material and BI 730357 among secondary outcomes. It does not report the numerical outcome results, the number included in the pharmacokinetic analysis set, or a detailed statistical analysis plan. The record gives study dates of 2018-09-10 and 2018-11-13 for start and primary completion, respectively.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS included all subjects in the TS who provided at least one value for primary or secondary PK endpoints and were not excluded due to relevant protocol deviations 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) :This subject set included all participants who were documented to have received one dose of trial medication.

6. Primary Endpoint

The registry lists the primary outcome as Mass Balance Recovery of Total [14C]-Radioactivity in Urine (Feurine, 0-tz), measured over Within 18 hours (h) predose, 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240, 240-264, 264-288, 288-312, 312-336 h after dosing on Day 1, continued in 24 h intervals, every 7 days from Day 21 until Day 50..

The primary endpoint is mass-balance recovery of total [14C]-radioactivity in urine. It represents the amount of radioactivity excreted in urine from dosing through the latest quantifiable time point across participants, expressed as a percentage of the administered dose. The record specifies a geometric mean as the summary measure and a geometric coefficient of variation as the dispersion measure.

Radiolabeling allows drug-related material to be tracked even when the original compound has been transformed into metabolites. Urinary recovery is one component of a mass-balance assessment: it describes radioactivity collected in urine, while the study objectives also refer to faecal recovery. This endpoint does not, by itself, identify every compound carrying the label or establish the route and timing of all drug-related material. Metabolite profiling and structural identification require examination of the collected biological samples.

The collection schedule spans multiple post-dose intervals, with later collection periods specified as well. The cumulative endpoint depends on the latest quantifiable data point across participants, rather than on a fixed endpoint time that is necessarily observed for everyone. The record does not report the observed geometric mean, the geometric coefficient of variation, or the amount recovered in urine. Those numerical findings are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as a geometric mean with geometric coefficient of variation. These summaries are often used for pharmacokinetic measurements because concentrations, exposure measures, and recovery measures can vary multiplicatively and may have skewed distributions. A geometric mean summarizes values on a logarithmic scale and expresses a central level after transforming back to the original scale. The geometric coefficient of variation describes relative spread on a multiplicative scale. This is general statistical context; the record does not provide the actual summaries or the individual observations.

What does the endpoint summarize?

The urinary recovery measure is cumulative over time: it is the fraction of the administered radioactivity excreted in urine through the latest quantifiable time point across participants, expressed as a percentage of the administered dose. In general, a cumulative measure combines information across collection intervals up to its endpoint. Its interpretation depends on the completeness and timing of sample collection, the measurement process, and how the end of the interval is determined. The registry specifies a detailed collection schedule, but it does not report collection completeness or the observed endpoint value.

The endpoint is described as total [14C]-radioactivity rather than solely unchanged BI 730357. General pharmacokinetic interpretation distinguishes tracking a radiolabel from measuring the parent drug alone: radioactivity can remain associated with drug-derived material after metabolism. The record separately lists maximum measured concentration and area under the concentration-time curve for both 14C-BI 730357-equivalent material and BI 730357. The registry does not provide numerical results for those outcomes or details of their calculation beyond their stated definitions.

Why use geometric summaries?

For positive measurements that vary by proportional rather than additive amounts, taking logarithms can make a distribution more suitable for familiar summaries and analyses. A geometric mean then reflects a central multiplicative level, while a geometric coefficient of variation expresses dispersion in relation to that level. These summaries are not interchangeable with an arithmetic mean and standard deviation. The choice of summary can affect how readers understand the distribution, so the stated measure and dispersion should be considered together. No distributional plots, participant-level values, or numerical geometric summaries are reported in the registry record.

Over-dispersion is a general concern when observed variability exceeds what a simple statistical model assumes. If a model understates variability, uncertainty estimates may be too narrow and tests may appear more decisive than warranted. For a small pharmacokinetic study, variability among participants and within collection measurements can affect precision. The registry record does not describe a model for over-dispersion, report a dispersion-adjusted analysis, or provide enough numerical results to assess this issue. This is a general methodological point, not a claim about the study's observed data.

What can a confidence interval tell a reader?

In general, a confidence interval conveys the precision of an estimated quantity by giving a range of values compatible with the data under the method's assumptions. A narrow interval indicates greater precision than a wide interval, but it does not remove possible bias or limitations in measurement and design. The registry record does not report confidence intervals for the primary endpoint or the listed secondary outcomes. No precision range should therefore be inferred from the enrollment figure alone.

The primary endpoint's definition uses the latest quantifiable data point across participants. In general, quantifiability limits can matter because measurements below an assay's quantification threshold may not be represented as ordinary numeric values. How such observations are handled can affect a cumulative endpoint, particularly at later collection times. The registry does not report the assay's quantification limit or the method used for values that were not quantifiable. It is therefore not possible to evaluate those choices from the record.

What does the planning illustration represent?

Any sample-size calculations described as planning illustrations are hypothetical design calculations based on an observed effect, not observed power for this completed study. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of the observed effect. Those assumptions describe a two-arm planning framework, whereas this study is recorded as single-group with no treatment comparator. Such illustrations do not establish the study's original design rationale, and the sample-size justification is not reported in the registry record. No numerical planning result is stated in the record.

In general, a planned sample size depends on the outcome, variability, target effect, analysis method, and desired operating characteristics. A planning calculation is not a substitute for observed uncertainty, and it cannot remedy missing outcome reporting. The record does not report an original sample-size justification, interim analysis plan, or detailed statistical plan. In particular, it does not identify a model for the primary endpoint, describe how missing or non-quantifiable measurements were treated, or state whether sensitivity analyses were conducted.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary urinary mass-balance endpoint and lists secondary outcomes for maximum measured concentration and area under the concentration-time curve for 14C-BI 730357-equivalent material and BI 730357. It reports four outcome measures overall, but descriptions for all of those measures are not reported in the registry record. The record also lists 0 analysis records. The existence of several outcomes does not show that statistical testing was performed, and no multiplicity adjustment or testing hierarchy is reported.

Multiplicity is a general issue that arises when several hypotheses are tested: without an appropriate plan, the chance of at least one apparently noteworthy result can increase. How that issue should be handled depends on the study questions and analysis plan. The registry record does not report an inferential testing strategy, adjustment method, or prespecified hierarchy, so the impact of multiplicity cannot be assessed from the available description.

The pharmacokinetic analysis set is defined as participants who provided at least one primary or secondary pharmacokinetic endpoint value and were not excluded for relevant protocol deviations or pharmacokinetic non-evaluability. The number meeting that definition is not reported. The record does not give participant-level missingness, reasons for missing measurements, or the handling of incomplete collections and values that were not quantifiable. Those details matter because the urinary endpoint is cumulative and its end point is defined by quantifiability across participants.

The registry does not describe imputation, sensitivity analyses, or the statistical handling of missing data. No conclusion about whether missingness could have affected the estimated endpoint is possible without those details and the numerical results. The analysis population and missing-data methods should therefore be regarded as incompletely documented 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 safety record lists 6 participants at risk for serious adverse events, with 0 affected, and records 0 deaths. For other adverse events, 6 participants were at risk and 4 were affected. These are counts recorded for the BI 730357 group. The record does not identify serious adverse-event terms, and its list of top serious terms is empty.

These figures describe events observed and recorded during the study; they are not comparative estimates. With no separate control group, the counts cannot show whether event frequency differed from another treatment or from a background rate. The registry does not provide event-level descriptions for the other adverse events in the information available for this summary, so their type, severity, timing, and relation to treatment cannot be characterized.

A zero count of serious events or deaths in this study does not establish that such events cannot occur. In general, safety interpretation depends on the size and duration of observation, event definitions, ascertainment, and the population studied. The record describes healthy male volunteers receiving a single dose, so these counts should be understood within that study context rather than generalized beyond it.

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

This study is designed to characterize the handling of a radiolabelled single oral dose of BI 730357 in healthy male volunteers. Its primary endpoint concerns recovery of administered radioactivity in urine, and its stated objectives also include faecal recovery and metabolite profiling. That design can address pharmacokinetic and mass-balance questions when the corresponding measurements and analyses are reported.

The registry record does not report the numerical primary endpoint result. It therefore does not show the observed urinary recovery percentage or its variability. Although the record names secondary pharmacokinetic outcomes, it does not report their numerical results either. The objectives and outcome definitions cannot be treated as findings, and no recovery amount or metabolite profile should be inferred from them.

The study is single-group and open-label, with no randomized comparator. It cannot establish a treatment difference against another intervention. It also does not answer whether the drug changes a clinical outcome: the described measurements concern radioactivity recovery and pharmacokinetics. The population is limited to healthy male volunteers, and the record does not support conclusions about other populations or treatment settings.

The safety counts indicate that no serious adverse events and no deaths were recorded, while other adverse events were recorded among participants. Those observations do not provide a controlled comparison or a definitive characterization of safety. The registry record gives limited detail about event types and does not report a comparative safety analysis.

The defensible interpretation is consequently narrow. The registry describes the design, objectives, endpoint definition, sample-collection schedule, and some safety counts. It does not report the numerical pharmacokinetic findings needed to answer the primary mass-balance question. A reader can understand what the study was intended to measure, but not determine from the record how much radioactivity was recovered or how precisely that quantity was estimated.

13. Why This Trial Matters Statistically

This study illustrates the difference between describing an endpoint and reporting its result. The registry gives a clear definition of urinary recovery as a percentage of administered radioactivity, identifies the summary measure, and outlines collection over time. Those elements help readers understand what the study set out to quantify. Without the observed estimate and its dispersion, however, the central mass-balance question remains unanswered in the registry record.

It also illustrates why study design must shape statistical interpretation. A single-group, open-label study can describe pharmacokinetic observations after dosing, but it does not provide a randomized treatment contrast. The appropriate focus is therefore on the quality, completeness, and precision of the measured recovery and exposure data, rather than on between-treatment effects.

The endpoint combines a radiolabel-based measurement with a collection schedule that extends across multiple intervals. In general, such measurements require attention to sample collection, quantifiability, and the definition of the cumulative endpoint. The registry provides some of that operational definition, including use of the latest quantifiable time point across participants, but does not report the data or analysis details needed to evaluate precision and completeness.

Finally, the record demonstrates that safety counts and pharmacokinetic objectives answer different questions. The event counts describe observations in the study group, while the primary endpoint concerns recovery of radioactivity. Neither should be interpreted as a comparative clinical effect. Clear separation of these questions is essential when reading early-phase studies, particularly when the record does not include numerical results for its principal pharmacokinetic outcomes.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpretation is that the registry record does not report the numerical result for the primary urinary recovery endpoint. It also does not report numerical findings for the listed secondary pharmacokinetic outcomes. As a result, the amount recovered, the variability of recovery, and the precision of the estimates cannot be evaluated.

The study has no comparator arm and is recorded as single-group and open-label. It cannot support a randomized comparison of treatments. The healthy male volunteer population and single-dose design also constrain the setting to which the described measurements apply; the record does not establish findings for other populations or dosing regimens.

The number in the pharmacokinetic analysis set is not reported, even though the record defines inclusion and exclusion criteria for that set. Participant-level completion of urine collections, handling of values that were not quantifiable, and missing-data methods are not reported. These omissions limit assessment of whether the cumulative endpoint represents complete collection through its specified time point.

The record does not report a detailed statistical analysis plan, confidence intervals, an original sample-size justification, or methods for multiplicity. It lists four outcome measures overall, while descriptions of all measures are not reported. Safety information is also limited: the record provides counts but does not provide further detail on other adverse events in the information available for this summary. These limitations concern what can be concluded from the registry record and do not establish that additional study information does not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study in Healthy Men to Test How BI 730357 is Processed by the Body — NCT03664011.
• Registry record last updated 2023-07-12; status last verified 2022-08.
• Results first posted 2023-07-12.
• 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 record describes a completed Phase I, open-label, single-group study in healthy male volunteers, with enrollment of 6. Participants received a single oral dose of 50 mg BI 730357 containing [C-14]-labelled and unlabelled drug substance. The primary endpoint concerns cumulative urinary recovery of total [14C]-radioactivity as a percentage of the administered dose, summarized by a geometric mean and geometric coefficient of variation.

The study objectives also include faecal recovery and metabolite profiling. The record lists secondary pharmacokinetic outcomes for maximum measured concentration and area under the concentration-time curve. Numerical results for the primary and listed secondary outcomes are not reported in the registry record. The safety record reports 0 serious adverse events, 0 deaths, and 4 participants affected by other adverse events. No separate comparator group is described.