This Study Tests BI 1467335 in Healthy Male Volunteers. The Study Tests How Different Doses of BI 1467335 Are Taken up and Handled by the Body: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for This Study Tests BI 1467335 in Healthy Male Volunteers. The Study Tests How Different Doses of BI 1467335 Are Taken up and Handled by the Body (NCT03382509), a randomized phase 1 study. The primary outcome is Fraction of [14C]-Radioactivity Excreted in Urine as Percentage of the Administered Oral Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe(Urine,0-t2)).

2. Clinical Question

The trial’s focus was drug disposition: how the radiolabelled compound and its metabolites were handled by the body, including mass balance, excretion pathways, and metabolism. Its primary endpoint was urinary recovery of radioactivity rather than a clinical outcome or a comparison of symptom improvement.

The registry describes a Phase I, open-label trial in healthy male volunteers. It lists randomized allocation but also labels the model as single group. The posted primary results are organized by single-dose and multiple-dose regimen. Because no untreated or placebo arm is reported, these results describe the measured excretion fractions in the two regimens; they do not establish a treatment effect against no treatment.

3. Trial Design

The registry describes a Phase I, open-label trial of [14C]BI 1467335 administered as an oral solution, with single-dose and multiple-dose components. It lists randomized allocation, no masking, and a single-group model. The reported outcome groups are the BI 1467335 10 mg single-dose group and the BI 1467335 10 mg multiple-dose group.

The posted primary endpoint summaries include 8 subjects in each regimen group. The registry record reports an overall enrollment of 16. The primary analysis population was the pharmacokinetic parameter analysis set: subjects from the trial set who provided at least one primary or secondary pharmacokinetic parameter not excluded because of a protocol deviation relevant to statistical evaluation of pharmacokinetic endpoints.

The trial’s stated primary objective was to assess mass balance, excretion pathways, and metabolism after a single oral dose of radiolabelled BI 1467335. The brief description notes that a selected number of subjects received the radiolabelled compound after preceding treatment with non-radiolabelled BI 1467335 once daily for 27 days. Secondary objectives concerned basic pharmacokinetics after single and multiple doses and the drug’s metabolites.

The registry’s secondary-outcome descriptions also refer to a 10 mg tablet once daily over 40 days, with a single 10 mg radiolabelled dose on Day 28. These descriptions are part of the registered outcome wording; the posted record does not provide a fuller account of the regimen or explain how the descriptions relate to one another. The trial is marked completed. Its start date is 2018-01-12, and its primary completion date is 2018-04-19.

The open-label designation means masking is listed as none. The record does not describe a separate placebo or untreated comparison group. Although allocation is listed as randomized, details of the randomization procedure 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 sites which would then ensured that all participants met all inclusion/exclusion criteria. Participants were not to be entered to trial treatment if any one of the specific entry criteria were not met.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic parameter analysis set (PKS): This subject set included all subjects of the TS who provided at least 1 primary or secondary PK parameter that was not excluded because of protocol deviations relevant to the statistical evaluation of PK endpoints.

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 set included all participants who received at least 1 dose of trial medication.

6. Primary Endpoint

The registry lists the primary outcome as Fraction of [14C]-Radioactivity Excreted in Urine as Percentage of the Administered Oral Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe(Urine,0-t2)), measured over 2 hours (h) prior to drug intake at Day 1 (SD group) and at the following intervals on Day 1 (SD group) and Day 28 (MD group): 0 to 4, 4 to 8, 8 to 12, 12 to 24 hours and every 24 hours thereafter from day 1 to day 14 following drug intake..

The primary endpoint is the fraction of administered [14C] radioactivity excreted in urine, expressed as a percentage of the oral dose, from the start of collection through the last quantifiable time point. The registry identifies the reported summary measure as a geometric mean and the dispersion measure as a geometric coefficient of variation.

This endpoint addresses drug disposition. After a radiolabelled dose, measured radioactivity can be used to track the administered compound and material derived from it. Urinary recovery therefore contributes information about an excretion pathway and about the amount of administered radioactivity accounted for in urine during the stated collection period. It does not, by itself, describe all routes of elimination or identify every chemical form present in the urine.

The collection schedule begins with a pre-dose interval and then specifies intervals on Day 1 for the single-dose group and Day 28 for the multiple-dose group, followed by daily intervals through Day 14 after drug intake. The endpoint definition refers to the last quantifiable time point, so the result depends on the recorded measurements being quantifiable over the collection period.

In general, a geometric mean summarizes values on a multiplicative scale and is often used for pharmacokinetic measures that are not well represented by an arithmetic average. The geometric coefficient of variation describes relative variability on that scale. Neither summary indicates the full distribution of individual measurements, and the registry does not provide individual-level values in the posted primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a pharmacokinetic disposition measure: urinary excretion of administered [14C] radioactivity, expressed as a percentage of the oral dose. The registry reports a geometric mean and geometric coefficient of variation for each regimen group. The result is summarized separately for the single-dose and multiple-dose groups rather than as a reported estimate of a contrast between them.

What does the geometric mean describe?

In general, the arithmetic mean is formed by adding observations and dividing by the number of observations. The geometric mean instead summarizes values on a multiplicative scale. It is commonly used for pharmacokinetic measurements when values are positive and variation is more naturally described proportionally than by equal absolute increments. It can be useful when a few relatively large observations would strongly affect an arithmetic mean.

The registry identifies the endpoint parameter as a geometric mean, but does not provide the individual observations or a fuller description of the calculation. The posted figures should therefore be read as the registered group-level summaries, not as values that permit reconstruction of the underlying observations. The geometric mean is also not the same as a median, and the record does not report a median for this endpoint.

What does the geometric coefficient of variation describe?

In general, a coefficient of variation expresses variability relative to a measure of central tendency. A geometric coefficient of variation is used with summaries on a geometric scale. It conveys relative dispersion, whereas a confidence interval conveys uncertainty about an estimated quantity. The two have different interpretations: a dispersion measure describes variation among observations, while a confidence interval describes the precision of an estimate under a specified statistical model.

The posted geometric coefficients of variation are 2.68 in the single-dose group and 2.12 in the multiple-dose group. They are not confidence limits, and they do not show the minimum and maximum observed values. The registry does not report confidence intervals for the primary endpoint.

Why is a formal comparison not available?

The registry lists two regimen groups and records randomized allocation, but it also identifies the trial model as single group. It posts group summaries for the primary endpoint, while the analyses count is zero. No between-group estimate, standard error, confidence interval, or p-value is reported. Thus the numerical ordering of the two geometric means is descriptive; it should not be recast as a statistically tested difference.

In general, a comparative analysis needs a clearly defined contrast and a method for quantifying uncertainty around that contrast. Randomized allocation can support a comparison when the design and analysis are appropriately specified, but the allocation label alone does not provide those details. The registry does not report the randomization procedure or a statistical model for comparing the regimen groups.

How should the sample-size illustrations be read?

In general, a planning calculation asks how many participants might be needed under stated assumptions to detect a specified effect at a chosen significance level and power. Such a calculation is not a measure of the probability that a completed trial’s result is correct. The registry’s planning description characterizes its calculations as illustrations based on an observed effect, equal allocation, a two-sided significance level of 0.05, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect.

These planning illustrations are not the trial’s original design justification and are not observed power. The registry does not report the trial’s own sample-size justification. The calculations also do not replace a confidence interval or a formal analysis of the posted endpoint. No planning values are reported in the registry record for this endpoint in the registry record for the posted results.

What assumptions remain unknown?

In general, statistical estimates rely on choices about the analysis population, measurement handling, and missing observations. The registry defines the pharmacokinetic parameter analysis set, but does not report how the primary endpoint was handled for subjects with incomplete collections or measurements below quantification. It does not describe an imputation procedure, a sensitivity analysis, or a model for repeated measurements.

Over-dispersion is a general concern when observed variability exceeds what a simple model assumes. If a method assumes less variability than is present, its uncertainty estimates can be too narrow. The registry does not report a comparison model or its variance assumptions for this endpoint, so no claim about over-dispersion in the analysis can be made. The geometric coefficient of variation is a descriptive measure and does not establish whether a model’s assumptions were met.

The primary results are therefore best read as concise descriptive summaries of urinary recovery in the two listed regimen groups. They provide neither a full account of individual pharmacokinetic profiles nor inferential estimates for a between-group difference.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists eight secondary outcomes, including plasma concentration and area-under-the-curve measures for radiolabelled equivalence and BI 1467335. No secondary results are posted, and the registry reports zero analyses. The record does not describe a plan for controlling multiplicity across the primary and secondary outcomes, such as a testing hierarchy or adjustment for multiple comparisons. That plan is not reported in the registry record.

Multiplicity matters in general because examining multiple outcomes or contrasts can increase the chance of at least one apparently unusual result when each is assessed separately. Whether and how that concern was addressed cannot be determined from the posted record. Since no secondary outcome results or formal tests are reported, the secondary outcomes should not be treated as corroborating or conflicting evidence about the primary endpoint.

The registry defines the pharmacokinetic parameter analysis set as subjects who provided at least one primary or secondary pharmacokinetic parameter that was not excluded because of a protocol deviation relevant to statistical evaluation. This describes an eligibility rule for the analysis population, but does not give a participant flow or show how many subjects were excluded from a particular endpoint analysis.

Missing-data procedures are not reported in the registry record. In particular, the record does not state how incomplete urine collections, missing time points, or measurements below quantification were handled. It also does not report a sensitivity analysis to assess the effect of missing measurements. These details limit assessment of how representative the group summaries are of all enrolled subjects and how the last quantifiable time point was determined for each subject.

The registry reports 8 subjects in each primary-result group, but does not separately report endpoint-specific completeness. The posted summaries should not be interpreted as proof that all measurements were available for every subject or collection interval.

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 serious adverse event figures are reported separately for the multiple-dose and single-dose groups. In the multiple-dose group, 0 serious adverse events are reported among 8 subjects at risk; in the single-dose group, 0 are reported among 8 subjects at risk. The registry also reports 0 deaths in each group. These are counts from the posted record, not estimates of the probability of a serious event.

The record lists other adverse events for 8 of 8 subjects in the multiple-dose group and 6 of 8 subjects in the single-dose group. The “other” category is distinct from the serious adverse event count in the record. It does not specify, in the information, the event types, severity, duration, or whether an event was considered related to treatment. No top serious adverse-event terms are listed.

Zero reported serious events does not demonstrate that serious events are impossible or that a regimen is safe in other populations. A small study in healthy male volunteers has limited ability to characterize uncommon events. The registry record does not provide further detail on event collection, attribution, or follow-up in the posted safety summary, so the counts should be interpreted narrowly.

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

The results describe urinary recovery of radiolabelled material after BI 1467335 in healthy male volunteers. For the primary endpoint, the registry reports geometric mean excretion fractions of 79.0 for the single-dose group and 83.7 for the multiple-dose group. The corresponding geometric coefficients of variation are 2.68 and 2.12. These values summarize the posted endpoint; they do not show the full distribution of individual measurements.

The numbers do not provide a formal comparison of the two regimens. No effect estimate for a between-group contrast, confidence interval, or hypothesis test is reported. The numerically larger mean in the multiple-dose group should not be interpreted as a statistically established difference. Nor does the urinary recovery endpoint by itself account for all routes of excretion or identify all chemical forms of the radiolabelled material.

The trial was designed around mass balance, metabolism, excretion, and pharmacokinetics, not a clinical outcome. The record therefore does not establish whether BI 1467335 improves or worsens a health outcome. It also does not support conclusions about use in patients or in populations beyond the healthy male volunteers described in the registry.

The safety counts show no serious adverse events and no deaths in either reported group. Other adverse events are reported in the groups, but the posted summary does not identify their nature or relationship to treatment. These observations are limited to the recorded trial groups and should not be generalized as proof that serious harms cannot occur.

Overall, the posted results are descriptive pharmacokinetic findings. They indicate the recorded group-level urinary recovery and safety counts, while leaving uncertainty about comparative effects, individual variability, incomplete measurements, and the broader clinical meaning of the observations.

13. Why This Trial Matters Statistically

Early pharmacokinetic studies help characterize what happens to a drug after administration. A radiolabelled dose can support tracking of drug-related material, and urinary recovery is one part of a mass-balance assessment. In this trial, the primary endpoint focuses specifically on the fraction of administered radioactivity recovered in urine over the stated collection period.

Statistically, the distinction between a descriptive result and a comparative claim is central. The registry reports geometric mean summaries and geometric coefficients of variation for the single-dose and multiple-dose groups, but does not report a formal test or uncertainty interval for a contrast. This means that the posted figures describe each group without quantifying the precision of a difference between regimens.

The design information also deserves careful reading. Randomized allocation is listed, while the model is identified as single group and the available results are presented by regimen. Without a reported comparison analysis or further details of the allocation and analysis, the design label alone cannot supply the missing inferential information.

The endpoint’s scale is another statistical consideration. Pharmacokinetic measures are often summarized geometrically because proportional variation may be more meaningful than absolute variation. A geometric mean and geometric coefficient of variation are therefore useful summaries, but neither replaces individual data, a confidence interval, or a fully described analysis.

Finally, a small early-phase study can be informative about the measured pharmacokinetic question while remaining limited for safety characterization and broader clinical conclusions. The value of the record is its focused description of urinary excretion and related study objectives, alongside a clear view of what is not reported: formal comparative inference, detailed missing-data handling, and results for the listed secondary 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 record reports group-level summaries but no individual observations. It therefore does not permit assessment of the shape of the endpoint distribution, influential observations, or subject-level variation over time. The geometric coefficients of variation provide a relative dispersion summary, but do not resolve those questions.

No confidence intervals or formal comparisons are reported for the primary endpoint. The posted results consequently do not quantify the precision of the group means or the uncertainty around any difference between regimens. Details of the randomization method are also not reported in the registry record, despite the allocation label.

The primary endpoint depends on urine collection and quantification through the last quantifiable time point. The record does not explain how incomplete collections, values below quantification, or endpoint-specific missingness were handled. It also does not report the number of subjects contributing complete data at each collection interval.

The regimen descriptions include preceding treatment for 27 days in the brief description and refer to once-daily dosing over 40 days in secondary-outcome wording. The registry does not provide a fuller explanation of how these descriptions relate. This limits interpretation of the exact regimen chronology from the posted text alone.

The trial involved healthy male volunteers and was focused on pharmacokinetics and drug disposition. The record does not support extrapolation to patients or other populations. The safety summary provides counts without details on event types, severity, attribution, or follow-up. Secondary outcome results and a multiplicity plan are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: This Study Tests BI 1467335 in Healthy Male Volunteers. The Study Tests How Different Doses of BI 1467335 Are Taken up and Handled by the Body — NCT03382509.
• Registry record last updated 2021-06-22; status last verified 2021-06.
• Results first posted 2021-06-07.
• 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

NCT03382509 is a completed Phase I, open-label trial of BI 1467335 in healthy male volunteers. The registry lists randomized allocation and a single-group model. Its primary objective concerned mass balance, excretion pathways, and metabolism after an oral radiolabelled dose.

The primary endpoint was the percentage of administered [14C] radioactivity excreted in urine through the last quantifiable time point. The registry reports geometric mean values of 79.0 for the single-dose group and 83.7 for the multiple-dose group, with geometric coefficients of variation of 2.68 and 2.12, respectively. It reports 8 subjects in each group and no formal primary analysis.

The registry lists eight secondary outcomes, but no secondary results or analyses are posted. Safety summaries report no serious adverse events or deaths in either group. Missing-data methods, multiplicity handling, and a formal comparison between regimens are not reported in the registry record.