First in Man Trial of BI 113608: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for First in Man Trial of BI 113608 (NCT01540825), a randomized phase 1 study. The primary outcome is Clinically Relevant Abnormalities for Clinical Laboratory Evaluation, Vital Signs, Lung Function, Carbon Monoxide Diffusing Capacity of the Lung, ECG, Physical Examination, Orthostasis Test, Oxygen Saturation or Haemoccult Test.

2. Clinical Question

The study also explored pharmacokinetics, with secondary outcomes including Cmax, Tmax, AUC0-tz, AUC0-infinity and t1/2. Those measures describe drug concentration over time and exposure after dosing; their numerical results are not included in the registry record discussed in this explanation. The primary question is therefore about recorded clinically relevant abnormalities during the specified observation period, not about comparative efficacy or longer-term outcomes.

3. Trial Design

The registry identifies this as a Phase 1, randomized, double-blind, parallel study of single rising oral doses of BI 113608 in healthy male volunteers. It is placebo-controlled within dose groups. The listed BI 113608 doses range from 0.5mg to 200mg, and the control group received placebo. The intervention descriptions identify powder for oral solution.

The registry reports enrollment of 80. In the primary endpoint results, the placebo group has 20 participants and each listed dose group has 6. These are the denominators associated with the posted endpoint values; the registry record does not explain how participants were assigned to each group or why the groups have these sizes. It does not report the sequence or operational rules for moving between dose levels, so the phrase “single rising doses” should not be taken to establish details of dose-escalation decisions.

The primary endpoint is measured from administration of study drug until the end-of-study visit, up to 10 days, in the treated set. The registry marks the study completed and records start as 2012-02 and primary completion as 2012-05. It names Boehringer Ingelheim as sponsor.

The record describes safety and tolerability as the primary objective and pharmacokinetic exploration as a secondary objective. This design and endpoint focus on observations after single doses in healthy volunteers. The record does not report a longer follow-up period, a patient population, or a treatment-efficacy objective. Nor does it report the exact randomization procedure, concealment method, or masking procedures beyond the designation “double.”

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.

Only the first 6 of 11 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Treated set

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 which included all randomised subjects who received 1 dose of the study drug.

Only the first 6 of 12 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Clinically Relevant Abnormalities for Clinical Laboratory Evaluation, Vital Signs, Lung Function, Carbon Monoxide Diffusing Capacity of the Lung, ECG, Physical Examination, Orthostasis Test, Oxygen Saturation or Haemoccult Test, measured over From administration of study drug until end-of-study visit, up to 10 days.

The primary endpoint is the percentage of participants with clinically relevant abnormalities in a broad set of safety assessments: clinical laboratory evaluation, vital signs, lung function, carbon monoxide diffusing capacity of the lung, ECG, physical examination, orthostasis test, oxygen saturation or haemoccult test. The observation period runs from study-drug administration until the end-of-study visit, up to 10 days, and the stated analysis population is the treated set.

This type of composite safety endpoint can capture abnormalities arising in different systems rather than relying on a single measurement. General statistical explanation: combining several assessment types into one indicator can provide a broad summary of whether any qualifying abnormality was recorded. That breadth can be useful in an early-phase safety study, but it also means the headline percentage does not identify which assessment was performed, which specific abnormality occurred, or its severity. Those details would require component-level results, which are not reported in the registry record.

The posted value is 0.0 for placebo and for every listed BI 113608 dose group. This states that no participant in those group summaries was recorded as meeting the endpoint definition. It does not establish that every measured value was identical, that no non-qualifying changes occurred, or that no adverse events were reported. Adverse events are reported separately from this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: a binary endpoint classifies each participant according to whether an event or condition was recorded. The registry expresses the primary endpoint as a percentage of participants. Here, the reported percentage is 0.0 in placebo and in every listed BI 113608 dose group. The record also gives the group denominators: 20 for placebo and 6 for each dose. It does not report confidence intervals or an inferential comparison for this endpoint.

What does a percentage summarize?

A percentage turns the number meeting a definition into a value relative to the group being described. It is useful for comparing summaries across groups with different denominators, but the percentage alone does not convey its precision. The denominator gives important context: a percentage based on a small group can be more sensitive to each individual outcome than a percentage based on a larger group. General statistical explanation: uncertainty intervals help describe the range of event probabilities compatible with the observed data, under the assumptions of the chosen method. No such interval is reported for this primary endpoint.

How should a zero-event result be read?

A reported value of 0.0 means that no participant in that group was recorded as meeting the endpoint definition in the posted summary. It does not show that the underlying probability is exactly zero. It also does not rule out outcomes that were not part of the endpoint definition, changes that did not meet the clinical relevance criterion, or events occurring outside the observation period. General statistical explanation: rare events may not appear in a small study even when their underlying probability is not zero. The registry results therefore describe what was observed, rather than providing a guarantee about future observations.

Why is a broad endpoint both useful and limited?

The primary endpoint brings together clinically relevant abnormalities from laboratory evaluation, vital signs, lung function, carbon monoxide diffusing capacity, ECG, physical examination, orthostasis testing, oxygen saturation and haemoccult testing. A combined indicator can help summarize a range of safety surveillance findings. However, its interpretation depends on the definitions and assessment procedures used. The registry record gives the endpoint description but does not report a component-level breakdown or the criteria used to decide when an abnormality was clinically relevant. The overall percentage cannot reveal which component would have contributed an event.

What does the missing two-arm comparison imply?

The registry indicates that values are missing or not estimable for a two-arm comparison for this binary percentage endpoint. It therefore does not provide an inferential dose-versus-placebo result for the primary outcome. The group values can be read descriptively, but no reported p-value or confidence interval establishes how precisely the groups differ, or whether a difference is compatible with chance. No recalculated comparison is presented in the registry entries. When a registry's own analysis is available, that analysis is the primary source for its stated comparison; the record does not provide one for this endpoint.

How do the planning illustrations differ from observed results?

General statistical explanation: sample-size planning illustrations ask how many participants per arm might be needed under stated assumptions to detect a chosen effect with a specified power and significance level. They are conditional planning calculations, not a description of what occurred in the trial. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. The illustrations are based on the observed effect and are not the trial's own design justification. The registry record does not report a sample-size justification for the trial. Any planning figures should not be called observed power or treated as evidence that this trial had adequate power for a safety comparison.

For time-to-event outcomes, the general distinction is that planning may be expressed as a total number of events, whereas other outcome types may be expressed as participants per arm. This trial's primary outcome is a binary percentage, not a time-to-event endpoint. No new sample-size estimate or effect calculation is made. The central statistical reading remains descriptive: the registry reports zero observed primary-endpoint percentages in the listed groups, without an inferential comparison or uncertainty interval.

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 113608 0.5mg", "BI 113608 1mg", "BI 113608 2mg", "BI 113608 5mg", "BI 113608 10mg")
n      <- c(20, 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  20  0  0.0  0.0  16.8  0.0  16.1  0.1  16.1
ARM  BI 113608 0.5mg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  BI 113608 1mg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  BI 113608 2mg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  BI 113608 5mg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  BI 113608 10mg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint combines several assessment domains, but the registry record does not report a component-level breakdown or explain how multiplicity across those assessments was handled. It also does not report a multiplicity adjustment strategy for the secondary pharmacokinetic outcomes. Those outcomes are listed as Cmax, Tmax, AUC0-tz, AUC0-infinity and t1/2, but their numerical results are not included in the record details. Whether additional analyses or endpoints were prespecified, and how they were treated statistically, is not reported in the registry record.

The registry identifies the treated set as the primary endpoint population. It does not describe how missing endpoint assessments were handled, whether all treated participants had complete assessment data, or how missingness was defined. The group sizes shown with the primary results do not by themselves establish completeness of follow-up or the analysis rules for participants with incomplete records. Details of the statistical analysis plan, including any planned sensitivity analyses, are not reported in the registry record.

The study is described as randomized and double-blind, but the record does not report the randomization method, allocation concealment, or details of maintaining the blind. No inferential comparison is reported for the binary primary endpoint because the registry indicates that values are missing or not estimable for a two-arm comparison. It does not report a p-value or confidence interval for that comparison. These omissions limit the ability to assess multiplicity, missing-data assumptions and inferential precision from the registry results alone.

The registry record also does not report interim analyses, a sample-size justification, or a detailed statistical plan. Their absence from the record is not evidence that any particular procedure was or was not used; these details are simply not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: retrograde amnesia (16.7%), concussion (16.7%), fall (16.7%), laceration (16.7%).

The registry reports serious adverse events separately from the primary endpoint. The serious-event count is 0 for placebo and for BI 113608 at 0.5mg, 1mg, 2mg, 5mg, 20mg, 50mg, 100mg, 150mg and 200mg. For BI 113608 10mg, it reports 1 serious adverse event among 6 participants at risk. The record lists Retrograde amnesia, Concussion, Fall and Laceration among the top serious-event terms, each with a displayed value of 16.7%. The registry record does not provide further context for interpreting the relationship between those terms and the group-level count in this summary.

Other adverse events are reported separately: placebo 2 among 20; BI 113608 0.5mg 3 among 6; 1mg 1 among 6; 2mg 1 among 6; 5mg 0 among 6; 10mg 3 among 6; 20mg 0 among 6; 50mg 0 among 6; 100mg 4 among 6; 150mg 0 among 6; and 200mg 2 among 6. These are counts, not percentages, and they should not be conflated with the primary endpoint.

Deaths are not reported in the registry record. The small groups and short follow-up of up to 10 days limit how much these event summaries can establish about uncommon or later events. The counts describe the posted record; they are not, by themselves, a comparative safety test.

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

The primary endpoint results show 0.0 for every posted dose group and placebo group: no participant in these group summaries was recorded as having a clinically relevant abnormality according to the endpoint definition during follow-up of up to 10 days. That is the direct descriptive finding. It applies to the treated set and the particular clinical assessments included in the composite endpoint.

The finding does not show that all clinical measurements were unchanged, or that no adverse events occurred. The endpoint is limited to clinically relevant abnormalities in the listed assessment domains, while the registry separately reports serious and other adverse events. Other adverse events are recorded in several groups, and a serious adverse event is reported in the BI 113608 10mg group. These separate summaries help explain why zero on the primary endpoint should not be interpreted as zero for every safety measure.

The posted endpoint values also do not establish that BI 113608 and placebo are equivalent. The registry does not report an inferential two-arm comparison, confidence intervals or p-values for this endpoint. Equal observed percentages cannot establish that the underlying event rates are the same. Small dose-group denominators also leave limited information about uncommon outcomes. The study's single-dose setting and follow-up of up to 10 days do not answer questions about repeated exposure or longer-term outcomes.

The record describes healthy male volunteers, so these results do not directly characterize outcomes in other populations. Nor does this endpoint establish efficacy: the stated objectives concern safety, tolerability and pharmacokinetics. Although pharmacokinetic outcomes are listed, their numerical results are not reported in the registry record. The results should therefore be understood as a bounded account of recorded events and abnormalities in this study, not as a general prediction for other settings.

14. Why This Trial Matters Statistically

Early-phase studies often focus on what happens after initial exposure, and the registry describes safety, tolerability and pharmacokinetics as the objectives of this trial. Statistically, such a setting highlights the difference between a descriptive observation and a precise estimate of risk. Reporting zero for a defined outcome is informative about the participants observed, but small group sizes constrain what can be inferred about events that are uncommon.

The dose-group structure also matters for interpretation. The posted primary endpoint results give a separate summary for each dose and for placebo, rather than a single pooled active-treatment estimate. That preserves the dose-specific presentation, but it leaves each dose group with a small denominator. The registry does not report an inferential comparison for these binary results, so the descriptive values should not be upgraded into a conclusion about similarity between treatment and placebo.

The broad primary endpoint combines multiple kinds of safety assessments. This can provide a compact overall indicator, but it conceals which assessment domains were most informative unless component-level results are available. The record also reports adverse events separately, demonstrating that the primary endpoint and adverse-event summaries answer different descriptive questions.

Finally, the record distinguishes trial enrollment from the group denominators reported for this endpoint, and names the treated set as the analysis population. Keeping population and denominator definitions visible is fundamental to interpreting percentages. These features make the trial a useful example of reading early-phase registry results cautiously: identify the endpoint, population, follow-up and actual group counts, then separate observation from statistical comparison and from broader claims.

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 broad, but the registry does not report the separate results for its component assessments or the criteria used to classify an abnormality as clinically relevant. Consequently, a reader cannot determine which assessment domains were most informative or examine their individual patterns from the endpoint summary alone.

Group sizes are limited: the primary endpoint is reported for 20 participants in placebo and 6 in each dose group. The registry provides no confidence intervals or p-values for this endpoint and no estimable two-arm comparison. The zero percentages therefore have limited precision and cannot rule out uncommon outcomes or establish equivalence between any dose and placebo.

Follow-up is described as up to 10 days after study-drug administration. The record does not report longer-term safety results, and the study concerns single oral doses in healthy male volunteers. The findings do not directly describe repeated dosing or populations other than those studied. The registry also does not report detailed missing-data handling, the randomization procedure, allocation concealment, or the complete statistical analysis plan.

Serious and other adverse events are reported as counts, but the registry entries do not include detailed event narratives, timing, duration, resolution, or judgments about causality. Deaths are not reported in the registry record. Numerical results for the listed pharmacokinetic outcomes are also not reported in the registry record. These gaps limit the scope of interpretation; they should not be filled by assumptions about the study's procedures or findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: First in Man Trial of BI 113608 — NCT01540825.
• Registry record last updated 2017-01-20; status last verified 2016-11.
• Results first posted 2017-01-20.
• 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

NCT01540825 is a completed Phase 1 randomized, double-blind, parallel, placebo-controlled study of single rising oral doses of BI 113608 in healthy male volunteers. The registry reports enrollment of 80, with primary endpoint results for a treated set and follow-up from administration until the end-of-study visit, up to 10 days.

The primary endpoint is the percentage of participants with clinically relevant abnormalities across specified clinical and physiological assessments. Its posted value is 0.0 for placebo and for every listed dose group from 0.5mg to 200mg. Serious and other adverse events are reported separately; the registry records 1 serious adverse event in the 10mg group and none in the other listed groups.

The study also lists pharmacokinetic outcomes, but their numerical results are not reported in the registry record. No inferential comparison is reported for the binary primary endpoint. The findings are descriptive and apply to the reported groups, endpoint definition and short follow-up.