A Study in Healthy Men to Test How BI 1265162 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 BI 1265162 is Taken up and Processed by the Body (NCT04267276), a non-randomized phase 1 study. The primary outcome is Part 1: Mass Balance Recovery of Total (C-14) BI 1265162-radioactivity in Urine.

2. Clinical Question

The study’s broader objective was to characterize how BI 1265162 is taken up and processed by the body. The registry describes intended assessment of excretion routes, mass balance, pharmacokinetics of the parent drug and known metabolites, total radioactivity, metabolite profiling and identification when suitable assays were available, and safety and tolerability. These aims are descriptive and pharmacokinetic; the record does not describe a comparison of clinical benefit against a control treatment.

Part 1 focused on intravenous administration, including the primary urine mass-balance endpoint. Part 2 investigated oral administration. The record also lists secondary pharmacokinetic outcomes for Part 1, including concentration-time measures for total radioactivity, BI 1265162, and metabolite M582, as well as a safety outcome. The listed outcomes indicate the kinds of measurements planned, but they do not establish that numerical findings were posted for each measure.

The enrollment is 7. The record does not say how those participants were distributed across the two parts, or whether both parts were completed. It therefore does not support a direct comparison between oral and intravenous administration. The primary question that can be addressed from the posted information is limited to the intended Part 1 urine-recovery measure; its observed value is not reported in the registry record.

3. Trial Design

This is a Phase 1 study sponsored by Boehringer Ingelheim. The registry lists a start date of 2020-02-18, a primary completion date of 2020-04-02, and a status of TERMINATED. Enrollment is 7, and the condition is Healthy Volunteers. The title specifies healthy male subjects.

The study is described as non-randomized, open-label, single-dose, and single-arm per trial part, with a mass-balance design. Part 1 investigated BI 1265162 administered intravenously; Part 2 investigated BI 1265162 administered orally. A single-arm design means the described part does not include a concurrent control arm. Open-label means masking is listed as none. The record does not report a randomized allocation process or a blinded assessment procedure.

The different routes are identified as separate trial parts, not as randomized treatment groups. The registry explicitly cautions that the arms are not a like-for-like control comparison. Accordingly, results from the two routes should not be interpreted as a controlled estimate of a route effect. The record does not state how many participants took part in each part, whether participants contributed data to both parts, or why the study was terminated.

The primary endpoint belongs to Part 1 and concerns urinary recovery of total C-14 BI 1265162 radioactivity after intravenous administration. The record describes a collection schedule extending from pre-dose through 192 hours after administration. It also lists concentration-time outcomes for radioactivity, the parent compound, and metabolite M582, plus a Part 1 adverse-event outcome. These descriptions characterize intended assessments; they are not numerical findings.

The registry does not report a sample-size justification, an enrollment target distinct from the listed enrollment, or a statistical analysis plan. It also does not report whether the study had interim analyses, whether Part 2 was completed, or the reason for termination. Those omissions limit what can be inferred about the conduct and intended analysis beyond the design features explicitly recorded.

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 parameter analysis set (PKS): This set includes all participants from the treated set (TS) who provide at least one pharmacokinetic endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetics or due to pharmacokinetic non-evaluability (as specified in the following subsection 'Pharmacokinetics'). Descriptive analyses of pharmacokinetic parameters will be based on the PKS.

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): The treated set includes all participants who were entered and treated with one dose of trial drug. The treated set will be used for safety analyses.

6. Primary Endpoint

The registry lists the primary outcome as Part 1: Mass Balance Recovery of Total (C-14) BI 1265162-radioactivity in Urine, measured over On Day -1 or Day 1 pre-dose (blank) sample, on Day 1 prior to start of urine collection voiding of the bladder, 0-4 , 4-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, and 168-192 hours after administration of BI 1265162 (C-14)..

The primary endpoint is Part 1 mass-balance recovery of total C-14 BI 1265162 radioactivity in urine. It is expressed as a percentage of the administered dose and refers to the total amount recovered over the interval from 0 to 192 hours after a single intravenous administration. The registry describes urine sampling at pre-dose and at intervals through the end of that collection period.

Mass balance is used to describe the measured recovery of a labeled compound and its radioactive material in collected excreta. In general, such measurements help characterize how much of the administered radioactive dose is accounted for in the collected material over the observation period. This endpoint is specifically urinary recovery; it is not, by itself, a complete measure of recovery through every possible route, nor does it identify the chemical form of every radioactive component.

The registry specifies that the endpoint is summarized using a geometric mean and a geometric coefficient of variation, calculated by noncompartmental analysis. A geometric mean is a summary suited to positive measurements that may be distributed asymmetrically. A geometric coefficient of variation describes relative spread on a multiplicative scale. These are general interpretations of the stated summaries, not additional results from this study.

The numerical geometric mean and geometric coefficient of variation are not reported in the registry record. Thus, the endpoint definition and analysis approach are available, but the observed urine recovery and its variability cannot be described from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: Pharmacokinetic studies describe how measured drug-related material changes over time and how it is distributed among collected samples. A mass-balance assessment focuses on accounting for administered labeled material in collected excreta. These methods describe exposure, recovery, or disposition; they do not automatically establish a clinical treatment effect.

What does the primary summary represent?

The primary endpoint is urinary recovery of total C-14 BI 1265162 radioactivity as a percentage of the administered dose over 0 to 192 hours after intravenous administration. The record specifies a geometric mean and geometric coefficient of variation, calculated by noncompartmental analysis. The geometric mean summarizes the central tendency of positive observations using a multiplicative scale. The geometric coefficient of variation describes relative dispersion on that scale, rather than the absolute distance between observations. These explanations are general; the registry does not report the actual summary values for this endpoint.

Noncompartmental analysis is a general approach to pharmacokinetic data that uses observed concentration-time measurements and numerical summaries without requiring the data to follow a specified compartment model. The registry identifies this approach for calculation of the geometric mean and geometric coefficient of variation. It does not report further implementation details, such as the specific data-handling rules or software used.

How should the concentration-time outcomes be understood?

The listed secondary outcomes include area under the concentration-time curve over 0 to 192 hours for total radioactivity, BI 1265162, and metabolite M582. In general, an area-under-the-curve measure summarizes concentration over time during a stated interval. The listed outcomes also include maximum measured concentration, commonly used to describe the highest observed concentration in the sampled profile. These definitions explain the types of quantities named in the registry; no numerical estimates for these outcomes are reported in the registry record.

The registry’s secondary-outcome descriptions concern Part 1. They do not provide a numerical oral-versus-intravenous contrast. More generally, comparing descriptive pharmacokinetic summaries across non-randomized trial parts would not be equivalent to a randomized route comparison, particularly when participant allocation and part-specific counts are not reported.

What does variability add?

General statistical context: a measure of central tendency alone does not show how much individual observations vary. A dispersion measure helps convey whether participants’ values cluster closely or are spread more widely. The geometric coefficient of variation is a relative measure that is suited to multiplicative variability in positive data. Its interpretation depends on the observed data and analysis details; neither the coefficient nor the individual observations are reported for the primary endpoint in this registry record.

A confidence interval, in general, describes a range of values compatible with the data and a specified statistical procedure, reflecting sampling uncertainty under the method’s assumptions. The record does not report a confidence interval for the primary endpoint, nor does it state that one was calculated. It is therefore not possible to describe the precision of the estimated mass-balance recovery using an interval.

How should the study structure affect interpretation?

The title describes a non-randomized, open-label, single-dose, single-arm design per trial part. There is no concurrent control group described. The intravenous and oral routes appear as separate interventions in separate parts, and the registry’s own caution says the arms are not a like-for-like control comparison. The general consequence is that descriptive values can characterize observations in a trial part, but they do not isolate a route effect from differences in participants, conduct, or other conditions. The record does not report enough detail to assess such factors.

The study’s enrollment is 7, and the adverse-event group is listed with 7 participants at risk. Small studies generally provide limited information about uncommon outcomes and may yield uncertain estimates, even when the reported counts are complete. This is a general statistical consideration, not a calculated power assessment or a claim about the study’s observed precision. The registry does not report a sample-size justification or a formal precision target.

There are no analyses listed in the registry record. It does not report model specifications beyond the stated noncompartmental analysis for the primary summary, inferential tests, confidence intervals, covariate adjustment, or a prespecified hierarchy among outcomes. These absences mean that the posted record permits only a limited description of the analysis approach. They should not be filled in by assuming common practice.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary pharmacokinetic and safety outcomes. It does not report a statistical analysis plan describing how these outcomes were prioritized for inference, whether tests were planned, or whether any adjustment for multiple comparisons was intended. Multiplicity is a general concern when many outcomes or statistical tests are considered: without a prespecified strategy, the chance of at least one apparently unusual result can increase. No adjustment method or inferential results are reported, so no conclusion about multiplicity control can be made.

The record gives a primary pharmacokinetic analysis set definition: it includes treated-set participants who provide at least one primary or secondary pharmacokinetic endpoint and are not excluded because of a protocol deviation relevant to pharmacokinetic evaluation. The wording of that definition in the registry record ends incompletely. The record does not provide a full account of exclusions, participant-level analysis-set membership, or whether the stated set was used for every listed outcome.

Missing-data handling is not reported in the registry record. There is no description of how missing samples, measurements below assay limits, incomplete urine collections, or participant withdrawals were addressed. These are general issues that can affect pharmacokinetic and mass-balance summaries; whether any arose in this study is not reported. The record also does not report an imputation method or sensitivity analysis.

The enrollment is listed as 7, but the record does not state how many participants contributed to the primary endpoint. It therefore does not establish the analysis denominator for that outcome. Neither a sample-size justification nor a planned interim-analysis approach is reported. No additional design or analysis assumptions should be inferred from the listed enrollment alone.

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

For the group titled BI 1265162 - Intravenous, the registry lists 7 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 7 participants at risk and 4 affected. Deaths are listed as 0. The record provides no top serious adverse-event terms.

These counts describe participants in the recorded group. They do not give event counts, because one participant may have experienced more than one event; the registry summary does not report the number of individual events. It also does not report the specific terms for the other adverse events, their timing, severity details, or whether investigators judged them related to BI 1265162. The absence of serious-event terms is consistent with the reported count of 0 affected participants, but does not provide additional event-level information.

General statistical context: a zero count in a small study is not evidence that the underlying risk is zero. These safety data are descriptive and lack a concurrent control group, so they cannot distinguish events associated with study participation from events that might occur otherwise. Part-specific safety figures for oral administration are not reported in the registry record.

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

The record establishes that the study was designed to investigate mass balance, pharmacokinetics, metabolism, excretion, safety, and tolerability of BI 1265162 in healthy male subjects. It specifies an intravenous Part 1 and an oral Part 2, with a single-dose, open-label, non-randomized, single-arm design per part. For Part 1, the primary endpoint was the percentage of the administered intravenous dose recovered as total C-14 radioactivity in urine through 192 hours.

The primary endpoint’s numerical result is not reported in the registry record. The record therefore does not show the amount of urinary recovery, the variation among participants, or the precision of the estimate. Numerical results for the listed concentration-time outcomes are also not reported. The endpoint descriptions should not be mistaken for observed pharmacokinetic findings.

The safety summary records 0 participants with serious adverse events, 4 with other adverse events, and 0 deaths among 7 listed at risk in the intravenous group. These are descriptive counts. They do not establish causality, comparative safety, or the frequency of particular event types, and no corresponding oral-group figures are reported.

The posted information does not establish a difference between routes, a treatment effect, or a clinical benefit. It also does not provide enough detail to evaluate the analysis population for the primary outcome, missing observations, the reason for termination, or the intended statistical handling of the multiple outcomes. The study’s design can support descriptive characterization when results are available, but the numerical findings needed for that characterization are absent from the registry record.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between an endpoint definition and an endpoint result. The registry gives a clear description of a mass-balance measure, its unit, collection interval, and stated summary method. Yet without the numerical estimate and its variability, the principal quantitative question cannot be answered from the posted record. Statistical reporting needs both a defined estimand and observed results to communicate what the data indicate.

The design also highlights why study structure matters. A non-randomized, open-label, single-arm trial part can describe pharmacokinetic observations, but it does not create a concurrent control comparison. Although intravenous and oral administration are both named, they are separate parts, and the record cautions against treating their arms as like-for-like controls. That distinction prevents descriptive measurements from being read as a causal route comparison.

The adverse-event summary offers another useful reporting lesson. Counts of affected participants are informative as a basic description, but they do not reveal event terms, attribution, event-level frequency, or comparative risk. The count of 0 serious adverse events in the listed intravenous group should be understood within the limited enrollment and the absence of a control group, rather than as a broad estimate of safety.

Finally, a registry record can document intended assessments while leaving key analytic details unresolved. Here, the record does not report a statistical plan, sample-size justification, missing-data methods, or numerical pharmacokinetic results. Recognizing these gaps is part of sound statistical interpretation: it separates what the study set out to measure from what its posted record allows readers to conclude.

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 principal limitation for interpretation is that the numerical primary endpoint is not reported in the registry record. Although the geometric mean, geometric coefficient of variation, and noncompartmental analysis are specified, the values needed to describe recovery and its variability are absent. Numerical estimates for the listed secondary pharmacokinetic outcomes are also not reported.

The record lists enrollment of 7 but does not report how many participants contributed to the primary endpoint or how participants were distributed between the intravenous and oral parts. It also does not state whether both parts were completed. The study status is TERMINATED, but the reason for termination is not reported in the registry record.

The design has no randomized comparator, and the registry cautions that the arms are not a like-for-like control comparison. Consequently, the record cannot support a controlled comparison of administration routes. The available safety summary is limited to the intravenous group and does not include event terms for the other adverse events, attribution, or a comparator group.

Important analysis details are not reported, including the sample-size justification, statistical analysis plan, missing-data handling, and any multiplicity strategy. The pharmacokinetic analysis-set description is incomplete in the registry record, and participant-level analysis-set membership is not given. Without these details and the numerical endpoint results, assessment of precision, robustness, and potential bias is limited.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study in Healthy Men to Test How BI 1265162 is Taken up and Processed by the Body — NCT04267276.
• Registry record last updated 2022-06-01; status last verified 2022-05.
• Results first posted 2022-02-23.
• 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

NCT04267276 is a Phase 1 study sponsored by Boehringer Ingelheim in healthy male subjects. It is described as non-randomized, open-label, single-dose, and single-arm per trial part, with intravenous BI 1265162 in Part 1 and oral BI 1265162 in Part 2. Enrollment is 7; the status is TERMINATED. The registry lists a start date of 2020-02-18 and a primary completion date of 2020-04-02.

The primary Part 1 endpoint is urinary recovery of total C-14 BI 1265162 radioactivity as a percentage of the administered intravenous dose over 0 to 192 hours, summarized by geometric mean and geometric coefficient of variation using noncompartmental analysis. The numerical result is not reported in the registry record. For the intravenous safety group, 0 participants had serious adverse events, 4 had other adverse events, and 0 deaths were listed among 7 at risk. The record does not describe a controlled route comparison or report numerical pharmacokinetic estimates.