A Study in Healthy Men to Test How Well Different Doses of BI 3731579 Are Tolerated: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in Healthy Men to Test How Well Different Doses of BI 3731579 Are Tolerated (NCT06429137), a randomized phase 1 study. The primary outcome is Occurrence of Any Treatment-emergent Adverse Event (AE) Assessed as Drug-related by the Investigator.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, single-blind, parallel-group, placebo-controlled trial of single rising doses of BI 3731579 in healthy male subjects. The registry describes the design as partially randomized. It lists eight active-dose groups, ranging from 6 mg through 600 mg, and a placebo group. Each active-dose group had 6 participants in the posted primary outcome results; the placebo group had 15. These are group-specific figures, not a basis for inferring allocation beyond what the record states.

Each active-dose group received one oral dose of BI 3731579 as film-coated tablets. The placebo group received a single oral dose of matched placebo in the same form. The arm descriptions specify administration with water following an overnight fast of at least 10 hours. Parallel-group means that the groups are described as separate groups rather than as participants who each received every dose. The registry does not report further details about dose escalation, sequence decisions, or whether any participant could enter more than one group.

The primary safety endpoint concerned investigator-assessed drug-related treatment-emergent adverse events. Its observation window began at drug administration and continued through the residual effect period, up to 4 days (96 hours). The treated set included participants who received at least 1 dose of trial drug and was used for safety analyses. The registry also lists pharmacokinetic outcomes: plasma area under the concentration-time curve over two intervals and maximum measured plasma concentration.

The trial is marked completed. Its recorded start date is 2024-07-08, and its primary completion date is 2025-05-19. The registry lists enrollment as 63. Details such as the randomization sequence, concealment procedures, planned dose-escalation rules, and the rationale for the group sizes 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 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.

Only the first 6 of 9 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The treated set (TS) included all subjects who were treated with at least 1 dose of trial drug and was used for the safety analyses.

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: The treated set (TS) included all subjects who were treated with at least 1 dose of trial drug.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Occurrence of Any Treatment-emergent Adverse Event (AE) Assessed as Drug-related by the Investigator, measured over From timepoint of drug administration plus the residual effect period, up to 4 days (96 hours) after drug administration..

The primary endpoint counts participants with any treatment-emergent adverse event that the investigator assessed as drug-related. A treatment-emergent event is one occurring after trial treatment begins; the registry specifies the observation period as from drug administration through the residual effect period, up to 4 days (96 hours). The reported measure is a count of participants, not a measure of event severity or duration.

This kind of endpoint is used in an early-phase trial to describe observed safety and tolerability after exposure to the study drug. Recording investigator-assessed relatedness distinguishes the endpoint from a count of every event, regardless of whether the investigator considered it related to treatment. That attribution is an assessment, not proof that the drug caused an event.

The posted primary results report zero participants in the placebo group and in dose groups 1 through 5 and dose group 7; the count is 2 in dose group 6, which received 360 mg, and 4 in dose group 8, which received 600 mg. These are counts, and the registry does not provide an inferential comparison or confidence intervals for this endpoint. The endpoint alone does not summarize all adverse events: the registry separately reports serious adverse events and other adverse events. Nor does it provide the pharmacokinetic results named among the secondary outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents the primary outcome as a binary event measure: each participant either was or was not counted as having an investigator-assessed drug-related treatment-emergent adverse event within the endpoint window. The posted values are counts of participants, rather than percentages or model-based estimates. Counts make the observed events transparent, but they do not by themselves express uncertainty or account for differences between groups.

What does a count of participants represent?

For this endpoint, a count records how many participants in a group met the endpoint definition. The corresponding group size is also reported: 15 for placebo and 6 for each active-dose group. A count of zero means no participant in that group was counted for this particular endpoint during its stated window. It does not mean that no other kind of adverse event occurred, that no event occurred outside the window, or that the underlying risk is zero. The registry separately records other adverse events and serious adverse events, which use different categories.

In general, binary outcomes can be compared using an absolute difference in event proportions, a relative measure, or a statistical model. Such comparisons require a clearly specified analysis and suitable handling of uncertainty. The registry does not report an inferential comparison for this primary outcome. It also flags that values were missing or not estimable for a two-arm binary comparison. No comparison estimate, confidence interval, or p-value for the primary endpoint is reported in the registry record.

Why is uncertainty important with small groups?

In general, estimates based on few participants can be imprecise: one or a few additional observations can materially change the estimate. This is especially relevant when event counts are zero or low. A zero observed count is not equivalent to evidence that an event cannot occur. Confidence intervals are one way to communicate uncertainty around an estimate; their width depends on the data and the method. No confidence intervals are reported for these outcome counts, so the degree of statistical precision cannot be assessed from the posted results.

In general, tests of significance address compatibility between data and a specified null hypothesis under stated assumptions. They do not establish that groups are equivalent when a test is not significant, and they do not replace an estimate with an uncertainty interval. Since the registry does not report an inferential test for the primary safety outcome, the counts should not be described as statistically significant or not statistically significant.

What do the secondary measures concern?

The listed secondary outcomes are AUC0-tz, the area under the plasma concentration-time curve from time 0 to the last quantifiable data point; AUC0-∞, the area under that curve from time 0 extrapolated to infinity; and Cmax, the maximum measured plasma concentration. These are pharmacokinetic measures, not adverse-event counts. In general, pharmacokinetic outcomes describe drug concentrations over time or a peak concentration. The numerical values, variability estimates, and analysis methods for these outcomes are not reported in the registry record.

The record lists four outcome measures and three secondary outcomes, but it does not report analyses for them. In general, analysis of pharmacokinetic measures may use summaries suited to their distributions and may examine dose relationships. The registry does not state which methods were used, whether values were transformed, how below-quantification observations were handled, or whether any dose-response model was fitted. Those details should not be inferred from the outcome names.

What can be inferred about planning?

The registry records sample-size planning assumptions for an illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with planning for a stated fraction of the observed effect. Such illustrations are planning scenarios, not observed power and not evidence that the trial was designed around a particular power target. The registry does not report a protocol-based sample-size justification or the underlying values for a planning calculation in this record.

In general, a planning calculation estimates the group size that would be needed to detect an effect under chosen assumptions. It does not describe the uncertainty of the observed trial result, and it cannot establish that a study had adequate power after the fact. The posted illustration should therefore be distinguished from the actual design and the reported group counts. The registry does not report the trial’s own sample-size rationale, any interim analyses, or a detailed statistical analysis plan.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Placebo", "Dose Group (DG) 1, 6 mg BI 3731579", "DG 2, 21 mg BI 3731579", "DG 3, 60 mg BI 3731579", "DG 4, 120 mg BI 3731579", "DG 5, 210 mg BI 3731579")
n      <- c(15, 6, 6, 6, 6, 6)
events <- c(0, 0, 0, 0, 0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Placebo  15  0  0.0  0.0  21.8  0.0  20.4  0.2  20.6
ARM  Dose Group (DG) 1, 6 mg BI 3731579  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  DG 2, 21 mg BI 3731579  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  DG 3, 60 mg BI 3731579  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  DG 4, 120 mg BI 3731579  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  DG 5, 210 mg BI 3731579  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The record identifies one primary safety endpoint and lists three secondary pharmacokinetic outcomes: AUC0-tz, AUC0-∞, and Cmax. It does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified strategy for controlling the risk of false-positive findings across multiple tests. Because numerical secondary-outcome analyses are not reported, the registry record does not allow assessment of how those outcomes were analyzed or interpreted.

The posted results list no outcome analyses for a two-arm binary comparison and indicate that values were missing or not estimable for that comparison. The registry does not report a statistical comparison for the primary endpoint. It is therefore not possible to describe a planned or completed inferential procedure beyond the descriptive counts presented.

The treated set is defined as participants who received at least 1 dose of trial drug and was used for safety analyses. This definition identifies the population for the reported safety results. The registry does not describe how missing endpoint information was handled, whether any participants had incomplete follow-up, or whether any imputation or sensitivity analysis was used. It does not report a separate analysis population for the pharmacokinetic outcomes.

In general, missing observations can affect an estimate if the likelihood of missingness is related to treatment or outcome. How important that issue is depends on how much data are missing and why. Those details are not reported in the registry record, so no assumption about the missing-data mechanism or its impact is warranted. The record also does not report interim analyses, stopping rules, or a detailed analysis plan. These omissions limit evaluation of multiplicity and analysis decisions; they do not imply that a particular procedure was or was not used outside what the registry records.

12. 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 counts of participants with serious adverse events, alongside the number at risk in each group. The registry reports zero serious adverse events in placebo and in every BI 3731579 dose group. It also reports zero deaths in every group, and the list of top serious-event terms is empty. These are the serious-event results recorded for this trial.

A zero count means no serious adverse event was recorded among the participants represented in that group during the registry’s reporting. It does not prove that the underlying chance of a serious event is zero. The active-dose groups each list 6 participants at risk, and placebo lists 15; with these group sizes, the record offers limited information about uncommon events. No confidence intervals or comparative statistical tests for serious adverse events are reported.

Serious adverse events are not the same category as all adverse events or as the primary endpoint. The primary endpoint counts events assessed by the investigator as drug-related, while the separate adverse-event data also list other adverse events. A serious-event count of zero should therefore not be read as a claim that there were no adverse events of any kind. The record reports other adverse-event counts in several groups, and those are a distinct safety summary.

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

The posted results describe a Phase 1 trial of single oral doses of BI 3731579 in healthy men. For the primary endpoint, the registry records no investigator-assessed drug-related treatment-emergent adverse events in placebo or in the 6 mg, 21 mg, 60 mg, 120 mg, and 480 mg groups. It records 2 participants for the 360 mg group and 4 for the 600 mg group. The observation window extended from drug administration through the residual effect period, up to 4 days (96 hours).

These findings are descriptive counts from the groups studied. They do not establish that the drug caused the reported events, nor do they establish that events in groups with zero counts cannot occur. Relatedness was assessed by the investigator. The separate serious adverse-event data show zero serious events and zero deaths in each group, but this does not mean that no other adverse events were recorded. Other adverse events are reported separately.

The registry does not report a statistical comparison, confidence intervals, or p-values for the primary endpoint. It therefore does not quantify the precision of a difference between any dose group and placebo. The group sizes are small, so the observations are limited in their ability to characterize uncommon events or to define event patterns reliably. The non-monotonic counts across dose groups also do not establish a dose-response relationship.

The record states that the trial aimed to investigate pharmacokinetics, and it names AUC0-tz, AUC0-∞, and Cmax as secondary outcomes. Their numerical results are not reported in the registry record. Accordingly, the posted safety counts cannot answer questions about plasma exposure or peak concentration. The record also does not provide results that support conclusions about repeated dosing, longer-term safety, or populations beyond the healthy male participants studied.

In general, an early-phase safety study can describe observations under its particular dose and follow-up conditions. It is not, by itself, a guarantee of safety or a definitive estimate of risk for other settings. The registry record supports a narrow account of the events counted during this trial and does not establish broader clinical effects.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how early-phase safety outcomes can be reported across several dose groups. The primary result is a set of participant counts, with the same reported group size for each active dose and a larger placebo group. That layout makes the observed pattern visible, while also emphasizing that the evidence comes from small groups and should be interpreted descriptively.

One important distinction is between an observed zero and a demonstrated absence of risk. In general, when few participants are observed, zero events can occur even when the underlying event probability is not zero. The record does not provide uncertainty intervals that would quantify this limitation. This matters when readers interpret groups with no recorded primary-endpoint events alongside groups with nonzero counts.

The trial also separates the primary endpoint from broader safety summaries. Investigator-assessed drug-related treatment-emergent adverse events are not interchangeable with other adverse events or serious adverse events. Reading those categories separately avoids treating different definitions as if they were the same outcome. The serious-event record reports zero serious events and zero deaths, while other adverse events are recorded in several groups.

Finally, the registry lists pharmacokinetic outcomes but does not report their numerical results or analyses. That gap illustrates why outcome names alone cannot answer the scientific question: interpretation requires estimates, measures of variability, and a description of the analysis. The record reports no inferential comparison for the primary binary outcome, so the observed counts should not be converted into claims of statistical evidence for differences. The trial’s value for statistical interpretation lies in understanding both what its descriptive data show and what remains unquantified.

15. 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 of the posted primary safety results is the small size of each active-dose group: 6 participants are listed in each. The placebo group has 15 participants. These group sizes restrict how much the counts can reveal about uncommon events, and no confidence intervals are reported to show the uncertainty around an estimated event frequency or group difference. The counts should not be treated as precise estimates of risk.

The registry does not report a statistical comparison for the primary binary outcome; it records that values were missing or not estimable for a two-arm comparison. No p-value or comparative confidence interval is available in the record. This prevents formal interpretation of differences between any dose and placebo. The registry also does not provide numerical results for the named pharmacokinetic outcomes, despite listing them as secondary outcomes.

The endpoint captures investigator-assessed drug-related events over a limited period: from administration through the residual effect period, up to 4 days (96 hours). It does not describe events outside that period. The registry’s primary endpoint and its broader other-adverse-event category differ, so their counts answer different questions. The record does not provide detail on missing outcome information, completeness of follow-up, or procedures for handling missing data.

Applicability is limited by the stated population of healthy male subjects and the single-dose design. The record does not establish how results would generalize to other populations or to repeated dosing. It also does not report detailed randomization procedures, the rationale for the sample size, an analysis plan, or interim-analysis information. These details are not reported in the registry record and should not be inferred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study in Healthy Men to Test How Well Different Doses of BI 3731579 Are Tolerated — NCT06429137.
• Registry record last updated 2026-08-10; status last verified 2026-06.
• Results first posted 2026-08-10.
• 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.

19. Record Summary

The registry record describes NCT06429137, a completed Phase 1, randomized, single-blind, parallel-group, placebo-controlled trial of single rising doses of BI 3731579 in healthy male subjects. Enrollment is listed as 63. The recorded start date is 2024-07-08, and primary completion is dated 2025-05-19.

The trial included placebo and BI 3731579 dose groups of 6 mg, 21 mg, 60 mg, 120 mg, 210 mg, 360 mg, 480 mg, and 600 mg. The primary endpoint was the count of participants with any treatment-emergent adverse event assessed as drug-related by the investigator during the period from administration through the residual effect period, up to 4 days (96 hours). The posted counts are 2 for the 360 mg group and 4 for the 600 mg group, and zero for placebo and the other active-dose groups.

The separate adverse-event record reports zero serious adverse events and zero deaths in each group. Three secondary pharmacokinetic outcomes are listed, but their numerical results are not reported in the registry record. No inferential comparison for the primary binary outcome is reported.