A Study to Test How Well Men Tolerate Different Doses of BI 3006337: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Test How Well Men Tolerate Different Doses of BI 3006337 (NCT05076422), a randomized phase 1 study. The primary outcome is Number of Subjects With Drug-related Adverse Events (AEs) After a Single Dose of BI 3006337.

2. Clinical Question

3. Trial Design

This completed Phase 1 study was randomized, single-blind, placebo-controlled, and used a parallel, sequential group design. It investigated single rising subcutaneous doses of BI 3006337 in healthy male subjects. The registry record lists an enrollment of 80. The dose groups were 0.2 mg, 0.5 mg, 1 mg, 2 mg, 4 mg, 8 mg, 15 mg, 30 mg, 50 mg, 100 mg, and 150 mg, alongside placebo.

The design description says randomization was partial and occurred within dose groups. It does not mean that every participant was randomized among every dose. Placebo participants were described as equally distributed across dose groups, but the registry record does not give further detail on the allocation procedure or the sequence used to progress through dose groups. The study was single-blind; which parties were masked is not reported in the registry record.

Each intervention was given once by subcutaneous injection after an overnight fast of at least 10 hours. The main objectives were safety, tolerability, and pharmacokinetics after single rising doses. The primary endpoint was the count of participants with drug-related adverse events. The registry also lists three secondary pharmacokinetic outcomes: area under the serum concentration-time curve from zero extrapolated to infinity, maximum measured serum concentration, and time to maximum measured serum concentration.

The study began on 2021-10-18, reached primary completion on 2023-03-03, and has completed status in the registry record. The record does not report a rationale for the enrollment target, details of dose escalation decisions, or a full statistical analysis plan. These omissions limit what can be concluded about design choices beyond the stated aims and structure.

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 12 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Treated set (TS): The treated set included all subjects who were entered and treated with any dose of the trial drug or placebo.

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 included all subjects who were entered and treated with any dose of BI 3006337 or placebo.

Only the first 6 of 13 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Drug-related Adverse Events (AEs) After a Single Dose of BI 3006337, measured over From 1 day pre-dose till end of trial, up to 40 days.

The primary endpoint counts participants who had an adverse event considered related to trial treatment after a single dose of BI 3006337. The assessment covered the period from 1 day pre-dose till end of trial, up to 40 days. A participant counts as having an event if at least one adverse event meets the registry’s treatment-relatedness criterion; the endpoint is a participant count, not a count of every event occurrence.

The registry description says medical judgment was used to decide whether there was a reasonable possibility that the event was causally related to the treatment. The judgment considered the reaction pattern, timing, de-challenge or re-challenge, and potential confounding factors, including concomitant medication, concomitant diseases, and relevant history. This means the endpoint combines clinical assessment of relatedness with a binary participant-level outcome: a participant either did or did not have a treatment-related event recorded for this measure.

Counting affected participants is useful in early-phase safety and tolerability research because it gives a direct account of how often participants experienced an event judged related to exposure. It does not describe the severity, duration, recurrence, or clinical consequences of each event. Those details are not captured by the primary count alone. Nor does a count establish causation; relatedness was determined through medical judgment, and the count reflects the registry’s reported classification.

The registry presents the endpoint as counts in each dose group and placebo group. Those counts should be read alongside the number of participants at risk in each group, while recognizing that the groups are small and differ in size.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary outcome is a count of participants who experienced at least one adverse event judged related to treatment. It is not a count of all adverse-event episodes. A participant with repeated events may still contribute to the endpoint as one participant with an event. This distinction matters because participant counts describe how many people were affected, whereas event counts describe the burden of all recorded episodes.

Because each participant is classified as having or not having the endpoint, the outcome is binary at the participant level. A group’s count must be interpreted in relation to the number of participants observed in that group. The registry gives both the affected count and the group size. The difference between groups in raw counts can be misleading when group sizes differ, so raw counts alone are not a sound basis for judging a treatment contrast.

Why is a comparison not available?

The registry record does not provide an estimated two-arm comparison for the binary primary endpoint. It notes that values were missing or not estimable for such a comparison. This is a limitation of the posted results, not evidence that the groups are equivalent. Without a comparative estimate, its uncertainty, and the method used to obtain it, the posted data do not quantify how much the endpoint may differ between a BI 3006337 dose group and placebo.

In general, a confidence interval describes uncertainty around an estimated quantity. For a binary outcome, an interval around a group frequency or difference can help show how much imprecision remains when the number of participants or events is limited. No such interval estimates for the primary endpoint are reported in the registry record. A formal statistical test would address a specified null hypothesis under stated assumptions, but no such test result is reported either. These general concepts explain what additional analyses might communicate; they do not supply missing results for this study.

How should zero counts be understood?

A zero count means no participant in that group was recorded as having the endpoint during the defined follow-up period. It is not the same as proving that the underlying event risk is zero. With limited observations, a group can have no recorded events even when the true chance of an event is not zero. General statistical methods can quantify uncertainty around a zero count, but the registry record does not report those estimates. The same caution applies to groups with one or two affected participants: those observations are descriptive and do not determine a stable underlying frequency.

What can be learned from the dose groups?

Multiple single-dose groups allow safety observations across a range of administered doses. However, a sequence of group counts does not itself constitute a dose-response analysis. Such an analysis would need a defined method for evaluating whether outcome frequency changes with dose and would need to account for the small, unequal group sizes and the placebo comparison. The registry record does not report a formal dose-response model, trend test, or inferential analysis of the primary endpoint. No dose-related pattern should therefore be inferred solely from which groups have zero, one, or two events.

The study is described as partially randomized within dose groups and parallel with sequential groups. These design features give context to the comparisons, but do not establish that the groups are interchangeable for every purpose. The registry record does not report enough detail to assess the randomization procedure, allocation concealment, or the exact sequencing decisions. Nor does it report an adjusted analysis of the endpoint.

What do the planning illustrations mean?

General sample-size planning uses assumptions about the effect to be detected, the significance level, allocation, and statistical approximation. The registry-linked planning illustrations are based on the observed effect, use a two-sided significance level of 0.05, assume equal allocation between two arms, and use a normal approximation. Their effect target is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, such planning values describe participants per arm; they are illustrations for future planning, not observed study results.

Such calculations do not show that the completed study had a particular probability of detecting an effect, and they do not replace a design-stage sample-size justification. The registry record does not report the study’s own sample-size justification or say that the planning assumptions were used to design the trial. No separate observed-power conclusion should be drawn from a calculation based on an observed effect.

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", "BI 3006337 0.2 mg", "BI 3006337 0.5 mg", "BI 3006337 1 mg", "BI 3006337 2 mg", "BI 3006337 4 mg")
n      <- c(19, 5, 6, 5, 6, 5)
events <- c(0, 0, 1, 0, 0, 2)
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  19  0  0.0  0.0  17.6  0.0  16.8  0.1  16.8
ARM  BI 3006337 0.2 mg  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  BI 3006337 0.5 mg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  BI 3006337 1 mg  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  BI 3006337 2 mg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  BI 3006337 4 mg  5  2  40.0  5.3  85.3  11.8  76.9  11.8  77.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary safety endpoint and three secondary pharmacokinetic outcomes: serum area under the concentration-time curve from zero extrapolated to infinity, maximum measured serum concentration, and time from dosing to maximum measured concentration. It does not report a multiplicity strategy, such as a hierarchy of hypotheses or an adjustment for testing several outcomes. The record also lists no analysis results for the secondary outcomes in the information used for this description. Without a reported testing strategy and results, no claim about confirmatory evidence across outcomes is warranted.

Missing-data methods are not reported in the registry record. The primary endpoint population is the treated set, defined as all subjects entered and treated with any dose of trial drug or placebo. That definition identifies who belongs in the intended safety population, but does not explain how incomplete follow-up, missing event assessments, or withdrawals were handled. The registry record does not report whether all treated participants contributed complete endpoint information through the stated follow-up period.

The registry record does not report an intention-to-treat analysis for this endpoint, a per-protocol population, imputation procedures, sensitivity analyses, or rules for handling participants with partial observation. These details affect how a count is interpreted if observation time differs or endpoint information is incomplete. The posted group counts should therefore be read as the reported treated-set results, without assuming unreported procedures for missing data or multiplicity control.

The record does not report interim analyses, a prespecified statistical analysis plan, or adjusted comparisons. These omissions do not prove that such procedures were absent; they mean that they are not reported in the registry record. Interpretation is accordingly limited to the described endpoint, population, time window, and posted arm-level counts.

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 report zero serious events in every listed group, including placebo and each BI 3006337 dose group. The corresponding numbers at risk are reported by group in the adverse-event results. No deaths are reported in any group. These figures are distinct from the primary endpoint, which counts participants with adverse events judged related to treatment; an event’s seriousness and its assessed relationship to treatment are separate classifications.

The adverse-event summary also reports participants with other, non-serious adverse events: 9 in the placebo group; 3 in each of the 0.2 mg, 0.5 mg, and 4 mg groups; 1 in each of the 1 mg and 2 mg groups; 0 in each of the 8 mg, 15 mg, and 30 mg groups; 3 in the 50 mg group; and 4 in each of the 100 mg and 150 mg groups. These are counts, not comparative estimates, and they should not be confused with the drug-related primary endpoint.

Zero serious events in this study means none were recorded among the participants at risk during the reported observation. It does not establish that serious events cannot occur, particularly when each group has limited observations. The registry record does not list serious-event terms or provide interval estimates for these safety counts. The figures are a descriptive account of what was recorded, not a guarantee about safety in other populations or settings.

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

The results describe a first-stage safety and tolerability investigation of single subcutaneous doses of BI 3006337 in healthy male subjects. They show the number of participants whom investigators judged to have had a treatment-related adverse event during the specified period. The registry reports nonzero primary endpoint counts in the 0.5 mg, 4 mg, 50 mg, 100 mg, and 150 mg groups, and zero counts in placebo and the remaining dose groups. Serious adverse events and deaths are recorded as zero across the groups.

These observations do not establish that BI 3006337 causes or prevents adverse events, nor do they demonstrate that one dose is safer than another. The study’s groups are small, the endpoint counts are sparse, and the registry does not report a comparative statistical estimate or a dose-response analysis. A zero count is not proof that an event is impossible, while a nonzero count is not by itself proof of causation. The primary endpoint’s relatedness classification is based on medical judgment, as described in the registry record.

The study also does not answer questions about repeated dosing, long-term exposure, use in people with health conditions, or use in populations other than healthy men. The intervention descriptions concern one dose and the primary safety observation period ends at up to 40 days. The registry record does not report results for the listed secondary pharmacokinetic outcomes in the information, so no pharmacokinetic findings should be inferred from the primary safety counts.

The strongest defensible reading is descriptive: the registry records few treatment-related events in these small groups, with counts varying across groups and no reported formal comparison. The results can inform understanding of what was observed in this trial, but do not provide a precise estimate of comparative risk or establish how the findings would apply elsewhere.

14. Why This Trial Matters Statistically

This trial illustrates why early-phase safety results are often most informative as careful descriptions rather than definitive comparisons. It includes placebo and multiple single-dose groups, creating an opportunity to observe adverse events over a range of administered doses. At the same time, the group sizes are limited and unequal, and the primary endpoint has few recorded events. Those features constrain the precision and interpretability of comparisons.

The primary outcome also demonstrates a distinction that matters in safety analysis: counting participants with an event is not the same as counting all event episodes, and treatment relatedness is not the same as seriousness. The registry reports separate information for the primary treatment-related endpoint and for serious and other adverse events. Keeping those classifications separate prevents the endpoint counts from being misread as a complete account of every safety dimension.

From a statistical perspective, sparse binary outcomes make uncertainty central. A group with no recorded events may still have meaningful uncertainty about the underlying frequency, and small differences in counts do not establish a trend. Here, the registry does not provide interval estimates, formal comparisons, or a dose-response analysis for the primary outcome. The absence of these results means that the data should not be treated as evidence of equivalence between dose groups or between BI 3006337 and placebo.

The trial’s value is therefore tied to the scope of its question: what was observed after single doses in healthy men over the stated period. The posted results communicate those observations, while also showing why sample size, follow-up, outcome definition, and reporting of inferential methods are essential to judging how precise and generalizable safety findings are.

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.

Several trial-specific limitations affect interpretation. The primary outcome is a participant count, and the groups have small, unequal sizes. The observed counts are therefore limited in their ability to characterize uncommon events or support stable comparisons. Zero values in a group should not be interpreted as evidence that the underlying event frequency is zero.

The registry record does not provide a formal comparison for the binary primary endpoint because values were missing or not estimable for a two-arm comparison. It also does not report confidence intervals, a dose-response analysis, or adjusted analyses. Consequently, the precision of the group-specific results and the evidence for differences between groups are not quantified in the posted results.

The trial studied healthy male subjects and single subcutaneous doses. The record does not establish whether the findings apply to other populations, repeated administration, or longer-term exposure. Follow-up for the primary endpoint was from 1 day pre-dose till end of trial, up to 40 days, so events outside that observation period are not addressed by the reported endpoint.

Important reporting details are absent: the statistical analysis plan, the sample-size justification, missing-data procedures, multiplicity handling, and further details of randomization and masking. The record also does not report the listed secondary pharmacokinetic results in the information available for this analysis. These limitations do not establish that procedures or outcomes were absent; they mark what is not reported in the registry record and therefore cannot be evaluated from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Test How Well Men Tolerate Different Doses of BI 3006337 — NCT05076422.
• Registry record last updated 2026-01-08; status last verified 2025-12.
• Results first posted 2026-01-08.
• 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

NCT05076422 is a completed, randomized, single-blind, placebo-controlled Phase 1 study of single rising subcutaneous doses of BI 3006337 in healthy male subjects. The registry lists enrollment of 80 and dose groups from 0.2 mg through 150 mg, alongside placebo. The trial began on 2021-10-18 and reached primary completion on 2023-03-03.

The primary endpoint was the number of participants with drug-related adverse events during the period from 1 day pre-dose till end of trial, up to 40 days. The posted counts range from zero to two across the dose groups; the placebo count is zero. Serious adverse events and deaths are recorded as zero in all groups. The registry does not report a formal comparative analysis or interval estimates for the primary endpoint, and it does not provide results for the listed secondary pharmacokinetic outcomes in the information. Interpretation is limited to these descriptive observations in the studied population and follow-up period.