A Study to Test How Different Doses of BI 3731579 Are Tolerated by Healthy People: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Test How Different Doses of BI 3731579 Are Tolerated by Healthy People (NCT06716190), a randomized phase 1 study. The primary outcome is Occurrence of Any Treatment-emergent Adverse Event Assessed as Drug-related by the Investigator.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, single-blind, parallel-group trial in healthy volunteers. The registry lists an enrollment of 30. Participants were assigned to placebo-matching BI 3731579 or one of three BI 3731579 dose groups: low, mid, or high. The trial also lists midazolam as an intervention. The record does not describe the details of sequence generation, allocation concealment, or how blinding was maintained, so those aspects are not reported in the registry record.

The trial’s stated objectives were to investigate safety, tolerability, pharmacokinetics, and pharmacodynamics after multiple rising doses. The brief summary describes dosing over 15 days. Arm descriptions state that participants in the active dose groups received single doses on Day 2 and Day 17, and twice-daily dosing from Day 4 to Day 16. The placebo-matching group also received tablets on Day 2 and Day 4 to Day 17. Midazolam was included in the trial, and the primary endpoint description specifically excludes its Day 1 microdose from the primary analysis.

The primary outcome was a safety measure: the number of participants with a treatment-emergent adverse event assessed by the investigator as drug-related. The registry also identifies plasma BI 3731579 exposure outcomes at steady state, including area under the concentration-time curve and maximum measured concentration. Numerical results for those pharmacokinetic outcomes are not reported in the registry record. A pharmacodynamic outcome is not described among the listed secondary outcomes.

The record gives a status of terminated, with a start date of 2024-12-18 and a primary completion date of 2025-05-19. The reason for termination is not reported in the registry record. No protocol-based sample-size justification or details of interim analyses are 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 prior to participation in the trial. The participants attended a specialist site which ensured that they (the participants) strictly met all inclusion and none of the exclusion criteria. The participants 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: Treated set (TS) - all participants who were treated with at least one dose of the trial drug.

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) - all participants who were treated with at least one dose of the trial drug.

6. Primary Endpoint

The registry lists the primary outcome as Occurrence of Any Treatment-emergent Adverse Event Assessed as Drug-related by the Investigator, measured over From first drug administration on Day 2 until last drug administration on Day 17, plus residual effect period (REP) for each intervention. Up to 19 days..

The primary endpoint counts participants who experienced at least one treatment-emergent adverse event that the investigator assessed as drug-related. It is a participant count, rather than a count of all adverse-event episodes. A participant with more than one qualifying event still contributes as a participant with an event for this endpoint.

The assessment period began with the first drug administration on Day 2 and continued until the last drug administration on Day 17, with the residual effect period for each intervention included. The registry gives the maximum duration as up to 19 days. The endpoint definition states that the primary analysis did not include the microdose of midazolam on Day 1.

In general, a drug-related adverse-event endpoint is used to describe the frequency of events considered by investigators to be related to treatment. Investigator attribution is a judgment, so the endpoint should not be read as proof that a drug caused an event. It also does not capture every aspect of safety: the count does not describe event severity, duration, recurrence, or the full clinical context. Those details are not included in the primary endpoint result presented in the registry record.

The endpoint is relevant to the trial’s safety and tolerability objective. It does not measure benefit for a health condition, and the study population consisted of healthy volunteers. Its results should therefore be interpreted as the reported safety observations within this trial and assessment period.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each treated participant either met the endpoint or did not, according to whether at least one treatment-emergent adverse event was assessed as drug-related by the investigator during the stated period. The registry reports counts by treatment group. These counts are descriptive; no inferential analyses are listed in the record.

What a participant count conveys

A participant count is a direct description of how many people met the endpoint in each group. It does not, by itself, quantify the precision of the underlying event frequency or establish whether group differences could be due to chance. Precision is commonly conveyed with a confidence interval. In general, a confidence interval describes a range of values compatible with the data under the method used; it is not a guarantee that the true value lies within that range. No confidence intervals for the primary endpoint are reported in the registry record.

Because the outcome is binary, comparisons can be expressed using measures such as a difference in event proportions or a relative measure. Such comparisons require a defined method and an estimate of uncertainty. The registry record does not report a two-arm estimate for this endpoint: the posted explanation says values are missing or not estimable for a binary-endpoint comparison. No comparison should be reconstructed from the displayed counts as though it were the sponsor’s analysis.

What the planning illustrations mean

The record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning calculations, not observed power and not evidence that the trial was designed with those assumptions. They do not establish that the study had an adequate sample size for its safety objective. Any sample-size figures should be read as hypothetical planning quantities under the stated assumptions, not as a description of what happened to participants.

In general, planning calculations depend on the chosen effect size, variability or event rate, significance level, allocation, and analysis method. If the observed effect is used as the starting point, the resulting illustration inherits uncertainty from the observed data. It is not an independent confirmation of an effect. The protocol’s own sample-size justification is not reported in the registry record.

Why sparse binary data need care

When event counts are small, estimates can be unstable, and some standard approximations may be unreliable. In general, methods for binary outcomes may use exact calculations or other approaches suited to sparse data, depending on the analysis plan. The statistical method actually used for a formal comparison is not reported in the registry record, and no formal analyses are listed. It would therefore be inappropriate to attribute a particular test or model to the trial.

Over-dispersion is a general issue in some data types when observed variability exceeds what a model assumes. It is more commonly relevant to count or clustered data than to a simple participant-level binary outcome. The primary endpoint is a participant count with an event, and the record does not report a model that accounts for over-dispersion. The essential reading point is that a small set of observed counts does not offer the same precision as a well-estimated comparative effect with uncertainty intervals.

How the analysis population affects interpretation

The primary analysis population is the treated set, defined as participants who received at least one dose of trial drug. This focuses the endpoint on participants exposed to trial treatment. It is not necessarily identical to the set of all participants enrolled or randomized, and the record does not provide a full account of participants excluded from this analysis population or their reasons. The endpoint description also states that the primary analysis excluded the Day 1 midazolam microdose. This boundary matters when interpreting which exposures contribute to the primary safety summary.

The registry lists secondary outcomes for BI 3731579 plasma exposure at steady state: area under the concentration-time curve over a uniform dosing interval and maximum measured concentration over that interval. Numerical values and statistical analyses for those outcomes are not reported in the registry record. The trial’s broader objectives include pharmacodynamics, but a numerical pharmacodynamic result is not reported among the listed secondary outcomes.

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-matching BI 3731579", "Low-dose Bid BI 3731579", "Mid-dose Bid BI 3731579", "High-dose Bid BI 3731579")
n      <- c(6, 8, 8, 8)
events <- c(0, 4, 0, 1)
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-matching BI 3731579  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Low-dose Bid BI 3731579  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8
ARM  Mid-dose Bid BI 3731579  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  High-dose Bid BI 3731579  8  1  12.5  0.3  52.7  2.2  47.1  2.8  48.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary safety endpoint and two secondary pharmacokinetic outcomes. It does not report a multiplicity strategy for handling several outcomes or comparisons. Without such a strategy, the record does not establish whether any formal testing across outcomes was planned or how the chance of false-positive findings would be addressed. No formal analyses are listed in the registry record.

Missing-data methods are not reported in the registry record. The posted primary counts do not describe how missing endpoint assessments, withdrawals, or incomplete follow-up were handled. The endpoint period is specified as extending from Day 2 through Day 17, plus each intervention’s residual effect period, up to 19 days, but the registry does not explain whether all participants completed that observation period.

The primary population is the treated set, defined as all participants treated with at least one dose of trial drug. This is the stated population for the primary endpoint. The registry record does not report a separate intention-to-treat analysis, per-protocol population, or sensitivity analysis. It also does not give enough detail to determine how participants who received different components of the trial interventions were included in every safety summary.

The primary endpoint explicitly excludes the Day 1 microdose of midazolam. This is an analysis-scope detail, not a general missing-data rule. The registry does not state whether interim analyses were conducted, and the analysis plan beyond the endpoint definition is not reported in the registry record. These omissions limit assessment of the planned handling of multiplicity, incomplete observations, and alternative analysis populations.

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 registry reports 0 related serious adverse events in each listed safety group: midazolam, placebo-matching BI 3731579, and the low-, mid-, and high-dose BI 3731579 groups. It also reports 0 deaths in every listed group. These are observed counts during the trial, not proof that serious events or deaths cannot occur.

The number at risk differs by group. The midazolam group lists 30 participants at risk; the placebo-matching group lists 6; and each BI 3731579 dose group lists 8. The registry reports other adverse events in 2 participants in the midazolam group, 3 in the placebo-matching group, 8 in the low-dose group, 1 in the mid-dose group, and 5 in the high-dose group. These are counts for the separate other-adverse-event category, not the primary drug-related endpoint.

The safety groups should not be added together to infer a total number of unique participants: the midazolam group may reflect exposure across the trial groups. The registry does not give event-level details or explain the relationship between all safety groupings and primary endpoint attribution. Serious-event counts, other-event counts, and investigator-assessed drug-related endpoint counts answer different questions and should be read separately.

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

The posted primary result describes the number of treated participants in each BI 3731579 group who experienced an investigator-assessed, drug-related treatment-emergent adverse event during the specified observation period. The counts were 0 of 6 for placebo-matching BI 3731579, 4 of 8 for low-dose BI 3731579, 0 of 8 for mid-dose BI 3731579, and 1 of 8 for high-dose BI 3731579. These results are descriptive observations from this trial.

They do not establish that BI 3731579 caused or did not cause any particular event. Investigator attribution is not the same as proof of causation, and the endpoint does not include every dimension of safety. The lack of a reported participant with the endpoint in a group does not demonstrate that the event risk is absent. The group sizes are limited, and the registry does not provide comparative estimates or confidence intervals for this binary outcome.

The results also do not show a consistent increase in the endpoint across the low-, mid-, and high-dose groups. The counts vary, with the largest count in the low-dose group, none in the mid-dose group, and 1 in the high-dose group. That pattern should not be overinterpreted as a dose-response finding or as evidence against one. The registry lists no formal analyses, and a two-arm comparison is not available for this endpoint.

The trial’s stated aims included pharmacokinetics and pharmacodynamics, but numerical results for the listed plasma exposure outcomes are not reported in the registry record. The posted primary result therefore does not answer those questions. The study was conducted in healthy volunteers, and the results do not establish what would occur in a different population. The reason the trial was terminated is not reported in the registry record; termination status alone does not explain the results.

14. Why This Trial Matters Statistically

This trial illustrates how safety outcomes can be reported as participant counts in randomized dose groups. A simple count is easy to interpret, but the group size is essential context: the same count can carry different levels of uncertainty depending on how many participants were observed. In this trial, the groups were small, and the registry does not provide confidence intervals or comparative estimates for the primary endpoint.

The endpoint also illustrates the distinction between an event and an event attributed to treatment. The primary outcome includes only treatment-emergent adverse events that the investigator assessed as drug-related. Separate safety summaries report serious adverse events, other adverse events, and deaths. These categories are not interchangeable. Clear interpretation depends on keeping the endpoint definition and its assessment period in view.

The trial’s randomized, single-blind, parallel-group design is relevant to how treatment groups were organized, but design labels alone do not establish the quality of allocation or blinding procedures. Those operational details are not reported in the registry record. Similarly, a stated statistical objective does not substitute for a documented analysis plan, and the registry lists no formal analyses for the primary endpoint.

Finally, planning illustrations based on the observed effect should not be confused with observed power or with the trial’s own sample-size justification. This distinction matters when interpreting small studies: planning calculations can show hypothetical requirements under assumptions, but they cannot add precision to the observed results. Here, the registry’s primary contribution is the set of reported safety counts, alongside clear limits on comparative inference.

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 primary endpoint is based on investigator assessment of whether an adverse event was drug-related. The registry does not provide event descriptions, severity, duration, timing by participant, or the reasoning behind those attribution judgments. The count therefore gives a limited view of the safety experience.

The group sizes are small: the placebo-matching group had 6 participants, and each BI 3731579 dose group had 8. The registry reports no confidence intervals or formal comparative analyses for the primary binary endpoint. The stated reason for the unavailable two-arm comparison is that values are missing or not estimable. This limits assessment of the precision of differences between groups.

The primary analysis population is the treated set, but the record does not describe participant flow in enough detail to assess incomplete follow-up, withdrawals, or missing endpoint observations. Missing-data handling and sensitivity analyses are not reported in the registry record. Further details of randomization, blinding, and the statistical analysis plan are also not reported in the registry record.

The primary safety outcome excludes the Day 1 midazolam microdose, while midazolam is separately represented in the safety summaries. These differences in scope require care when comparing endpoint counts with other adverse-event categories. The registry’s reason for termination is not reported, and the status itself does not explain whether the planned objectives were completed.

Although pharmacokinetics and pharmacodynamics are among the trial’s stated aims, numerical results for the listed pharmacokinetic outcomes are not reported in the registry record. The findings also come from healthy volunteers, so the population limits the scope of interpretation. These limitations mean the counts should be treated as descriptive trial observations rather than a precise estimate of comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Test How Different Doses of BI 3731579 Are Tolerated by Healthy People — NCT06716190.
• 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 describes a randomized, single-blind, parallel-group Phase 1 trial of BI 3731579 in healthy volunteers, with an enrollment of 30 and a status of terminated. Participants were assigned to placebo-matching BI 3731579 or low-, mid-, or high-dose BI 3731579; midazolam was also included. The primary endpoint counted treated participants with a treatment-emergent adverse event assessed as drug-related by the investigator, excluding the Day 1 midazolam microdose from the primary analysis.

The reported primary counts were 0 of 6 in the placebo-matching group, 4 of 8 in the low-dose group, 0 of 8 in the mid-dose group, and 1 of 8 in the high-dose group. The record lists 0 related serious adverse events and 0 deaths in the safety groups. It reports two secondary pharmacokinetic outcomes, but their numerical results are not reported in the registry record. The reason for termination, formal analyses, missing-data methods, and protocol-based sample-size justification are not reported in the registry record.