This Study in Healthy Men Tests How Different Doses of BI 1323495 Are Taken up in the Body and How Well They Are Tolerated.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for This Study in Healthy Men Tests How Different Doses of BI 1323495 Are Taken up in the Body and How Well They Are Tolerated. (NCT03588390), a randomized phase 1 study. The primary outcome is Percentage of Participants With Drug-related Adverse Events.

2. Clinical Question

This was a phase 1 study in healthy participants, not a trial of treatment for a disease. Its primary question concerns adverse events attributed as drug-related by the trial’s assessment. The posted percentages vary across the labeled dose groups: the registry reports 50.0% in Dose Groups 1 and 7, 33.3% in Dose Group 2, 16.7% in Dose Groups 4, 6, and 8, and 0.0% in Dose Groups 3 and 5. The placebo percentage is 6.7%. These are descriptive results for the groups as reported; the registry record does not give confidence intervals or a statistical test for these comparisons.

The secondary objectives described in the record concern pharmacokinetics, including dose proportionality, pharmacodynamics, and the relationship between pharmacokinetics and pharmacodynamics. The posted secondary outcome names are plasma area under the concentration-time curve from 0 extrapolated to infinity and maximum measured plasma concentration. Numerical results for those outcomes, and results for pharmacodynamic measures, are not reported in the registry record.

3. Trial Design

The registry identifies this as a phase 1, randomized, single-blind, parallel-group study with a partially randomized, placebo-controlled design. It was sponsored by Boehringer Ingelheim and is recorded as completed. The study start date is 2018-07-31, and the primary completion date is 2018-11-14. Enrollment is recorded as 63.

Participants were assigned to single oral doses of BI 1323495 or matching placebo across labeled dose groups. The arm descriptions state that participants took a film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. The numeric dose amounts and the specific allocation procedure are not reported in the registry record. Although the study title describes rising doses and the record identifies allocation as randomized, further details about how partial randomization was implemented are not reported.

The study was single-blind, but the record does not specify which people were unaware of treatment assignment or how blinding was maintained. The parallel-group design means the listed arms are presented as separate groups rather than as repeated treatment periods within each participant. Further details about visits, follow-up procedures, and dose-escalation decisions are not reported in the registry record.

The primary outcome was the percentage of participants with drug-related adverse events, assessed from drug administration until the end of the trial, up to 15 days. The primary outcome population was the treated set: participants documented to have received at least one dose of trial drug. The record describes pharmacokinetic and pharmacodynamic aims as secondary objectives. It lists plasma AUC0-∞ and Cmax among posted secondary outcomes, but numerical results for those outcomes are not reported in the registry record.

The record does not report the rationale for the enrollment target, the planned allocation proportions, or a detailed statistical analysis plan. It also does not report the exact doses assigned to each labeled dose group. Those omissions limit assessment of how the observed group sizes and comparisons relate to the original design.

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 to participate in the trial. Participants attended specialist site which would then ensure that all participants met all strictly implemented inclusion/exclusion criteria. Participants were not to be assigned to treatment groups if any one of the specific 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: Treated set (TS): This subject set included all subjects who were documented to have received at least 1 dose of trial drug. It was used for analysis of safety, demographic data, and baseline characteristics, as well as for the description of biomarkers.

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): This subject set included all subjects who were documented to have received at least 1 dose of trial drug. It was used for analysis of safety, demographic data, and baseline characteristics, as well as for the description of biomarkers.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Drug-related Adverse Events, measured over From drug administration until end of trial, up to 15 days..

The primary endpoint is the percentage of participants with drug-related adverse events. Its timeframe begins at drug administration and extends to the end of the trial, up to 15 days. The endpoint is analyzed in the treated set, defined in the registry record as participants documented to have received at least one dose of trial drug.

For an early safety and tolerability study, an adverse-event endpoint provides a direct descriptive account of events recorded after exposure. The drug-related qualification is important: the endpoint concerns events assessed as related to trial drug, not every event that occurred during follow-up. The registry record does not describe the criteria used to judge relatedness, how events were elicited, or who made those judgments.

The posted results give a percentage and group size for placebo and each BI 1323495 dose group. They report 6.7% for placebo; the percentages across Dose Groups 1 through 8 are 50.0%, 33.3%, 0.0%, 16.7%, 0.0%, 16.7%, 50.0%, and 16.7%, respectively. No uncertainty intervals or hypothesis-test results accompany these percentages in the registry record. Because the dose amounts are not reported, the percentages cannot be mapped to specific dose levels from this record alone.

This endpoint does not by itself describe the nature, severity, duration, or clinical consequences of the drug-related events. Nor does it answer the pharmacokinetic or pharmacodynamic questions. Those require separate outcome information, which is not reported in the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record reports arm-level percentages for a binary endpoint: whether a participant had a drug-related adverse event during the stated timeframe. A percentage expresses the observed share of participants in an arm with the event. It is a descriptive summary, not by itself a test of whether treatment groups differ. The posted group sizes are 15 for placebo and 6 for each BI 1323495 dose group.

What does a confidence interval add?

General statistical explanation: A confidence interval conveys the uncertainty around an estimate under a specified statistical method. For a percentage based on a small group, the interval can be wide because the estimate is based on limited information. The registry record does not report confidence intervals for the primary endpoint, so the precision of the arm-level percentages cannot be evaluated from intervals in this record.

When reading the results, it is useful to distinguish the observed percentage from the underlying event probability one might wish to estimate. The observed percentage is fixed for the participants recorded in the arm; uncertainty concerns how well it may represent the experience that would be seen in a broader population under comparable conditions. The percentages alone do not resolve that uncertainty.

Why is a direct treatment comparison not available?

The posted results give percentages within each arm, but they do not report an estimated contrast against placebo, an inferential test, or uncertainty around such a contrast. A difference between two displayed percentages is not automatically evidence of a reliable treatment effect. This is especially important with small groups, where the percentage can change substantially with the event status of a small number of participants. No recalculated treatment comparison is presented in the registry record.

The record identifies the study as randomized and partially randomized, single-blind, and parallel-group. Random allocation can help balance measured and unmeasured participant characteristics in expectation, but the record does not provide the detailed assignment procedure or explain which comparisons followed randomized assignment. The single-blind label indicates masking but does not identify who was masked. These design details matter when interpreting the degree of protection against bias; the missing information should not be filled in by assumption.

How should the dose-group pattern be read?

The primary percentages range from 0.0% to 50.0% among the labeled dose groups, with intermediate reported values of 16.7% and 33.3%. The pattern is not steadily increasing across the labels. Yet the numeric amounts assigned to Dose Groups 1 through 8 are not reported in the registry record, so the labels cannot be used to infer the size of a dose step or to test a dose-response relation. The trial objective refers to rising single doses, but the posted primary endpoint values alone do not establish an exposure-response or dose-response pattern.

General statistical explanation: In studies with event counts that vary more than a simple binomial model would expect, over-dispersion can make model-based uncertainty too narrow unless the analysis accounts for it. The registry record does not report a model for this binary endpoint or information that would establish whether over-dispersion is relevant. There is therefore no basis in the record to select or evaluate an over-dispersion adjustment.

What can the planning illustrations tell the reader?

The record describes sample-size planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. These are planning assumptions, not results from the trial’s original design. No numerical planning estimates are included in the record described for these results. Such illustrations should not be interpreted as observed power, nor as evidence that the trial was designed with those assumptions.

More generally, a sample-size illustration answers a planning question under its assumptions; it does not change the precision of the results already observed. The registry record does not report the trial’s original sample-size justification, so the planning assumptions do not establish why the actual group sizes were chosen.

The registry lists 2 secondary outcomes: plasma AUC0-∞ and Cmax. It also states secondary objectives involving dose proportionality, pharmacodynamics, and the PK/PD relationship. Numerical secondary results and the statistical methods for those analyses are not reported in the registry record. Consequently, the primary endpoint percentages should be kept separate from conclusions about drug exposure or pharmacodynamic activity.

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 1323495", "BI 1323495 Dose Group 1", "BI 1323495 Dose Group 2", "BI 1323495 Dose Group 3", "BI 1323495 Dose Group 4", "BI 1323495 Dose Group 5")
n      <- c(15, 6, 6, 6, 6, 6)
events <- c(1, 3, 2, 0, 1, 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 Matching BI 1323495  15  1  6.7  0.2  31.9  1.2  29.8  1.6  30.2
ARM  BI 1323495 Dose Group 1  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  BI 1323495 Dose Group 2  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  BI 1323495 Dose Group 3  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  BI 1323495 Dose Group 4  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  BI 1323495 Dose Group 5  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary safety endpoint and 2 secondary outcomes, alongside secondary objectives concerning dose proportionality, pharmacodynamics, and the PK/PD relationship. It does not report whether the analyses were organized into a prespecified testing hierarchy or whether any adjustment for multiple comparisons was used. The number and organization of planned comparisons across the dose groups are also not reported. Without those details, the record does not establish how the chance of false-positive findings across multiple analyses was addressed.

The primary endpoint results are descriptive percentages, with no p-values or confidence intervals reported. Accordingly, there is no reported inferential result for which a multiplicity adjustment can be evaluated. The presence of multiple arms and outcomes is a reason to interpret any isolated comparison cautiously, but the registry record does not support claims about the statistical significance of these results.

The primary analysis population is the treated set, defined as participants documented to have received at least one dose of trial drug. The record states that this set was used for safety, demographic data, baseline characteristics, and biomarker descriptions. It does not report whether there were additional analysis populations for the primary outcome or how participants with incomplete follow-up were handled.

Missing-data methods, the amount of missing primary endpoint information, and any sensitivity analyses are not reported in the registry record. The record also does not provide a detailed statistical analysis plan or a description of how drug relatedness was determined. These omissions limit assessment of analysis choices and potential bias. They do not establish that data were missing or that analyses were conducted in a particular way; those matters are simply not reported.

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 summary reports 0 serious adverse events in the placebo group and 0 in each BI 1323495 dose group. The registry also reports 0 deaths in each listed group. These figures describe the events recorded in the posted safety summary; they do not establish that the chance of a serious event is absent.

The record separately reports other adverse events: 2 in the placebo group; 3, 2, 1, 2, 1, 2, 3, and 2 in Dose Groups 1 through 8, respectively. These are counts in the registry’s other-adverse-event category and should not be substituted for the primary endpoint percentages, which concern drug-related adverse events. The record does not provide event descriptions or clarify the relationship between these entries and the primary endpoint assessment.

Zero reported serious events in these small groups is a limited observation, not a precise estimate of rare-event risk. The registry record does not report confidence intervals for the serious-event figures or further detail about event types and follow-up beyond the primary endpoint timeframe.

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

The posted results describe the percentage of treated participants recorded as having drug-related adverse events during follow-up of up to 15 days. The values vary across the labeled dose groups, while the placebo percentage is 6.7%. The registry also reports no serious adverse events and no deaths in the listed groups. Together, these results provide a brief account of the safety observations recorded for this study.

They do not establish that BI 1323495 is safe or unsafe in general, or that any dose is better or worse than placebo. The groups are small, uncertainty intervals and inferential comparisons are not reported, and the numeric dose amounts are absent. The group percentages therefore cannot support a precise comparison or a reliable conclusion about a dose-response relationship.

The results are specific to healthy male participants receiving single oral doses under the recorded fasting conditions. They do not describe repeated dosing, use in people with a medical condition, or outcomes beyond the reported follow-up. The registry record does not report detailed descriptions of the drug-related events, their severity, or how relatedness was assessed.

The study also sought pharmacokinetic and pharmacodynamic information. Although plasma AUC0-∞ and Cmax are listed as secondary outcomes, their numerical results are not reported in the registry record. The primary safety percentages therefore cannot answer questions about absorption, exposure, dose proportionality, or pharmacodynamic effects. The record’s stated objectives and its posted results should be distinguished: an objective describes what the study aimed to investigate, while a result requires reported outcome data.

In short, the record documents arm-level adverse-event percentages and a separate serious-event summary. It does not provide the uncertainty, detailed event information, dose amounts, or secondary outcome results needed for broader conclusions.

14. Why This Trial Matters Statistically

This trial illustrates a common challenge in early clinical research: descriptive safety results can be informative about what was recorded in each group while remaining imprecise as estimates of risk. The primary endpoint is a percentage, but its interpretation depends on the group size, the event definition, the follow-up window, and the way relatedness was assessed. The record gives the group sizes and timeframe, but does not report the criteria for determining whether an event was drug-related.

The variation across labeled dose groups makes clear why dose labels and actual dose amounts matter. The posted percentages do not rise steadily across the groups, but the numeric dose amounts are not reported. Without those amounts, a reader cannot connect the group pattern to dose level or assess dose proportionality. A stated objective to study rising doses is not a substitute for posting the actual doses and relevant results.

The study also shows why event percentages and serious-event summaries should be read as distinct measures. The primary endpoint concerns drug-related adverse events, whereas the safety summary separately reports serious events, deaths, and other adverse events. Keeping the categories separate prevents a reader from treating one measure as a proxy for another.

Finally, transparent reporting of confidence intervals, statistical comparisons, missing-data handling, and analysis populations would help readers judge precision and analysis choices. The registry record does not report several of these details. Recognizing what is reported, and what remains unreported, is an essential part of interpreting small early-phase studies without overstating what their results establish.

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 percentages are based on small arm sizes: n=15 for placebo and n=6 for each BI 1323495 dose group. No confidence intervals or inferential comparisons are reported, limiting assessment of precision and between-group uncertainty. The percentages should therefore be read as descriptive observations rather than as precise estimates or proof of differences.

The numeric dose amounts are not reported in the registry record. Although the study title and objectives describe rising single doses, the reader cannot map the labeled groups to dose amounts or examine the relation between dose and the primary endpoint using the posted results alone.

The record does not report details of how adverse events were elicited, how drug relatedness was judged, or the severity and duration of the events. It also does not report missing-data handling, a detailed statistical analysis plan, multiplicity procedures, or the specific allocation process for the partially randomized design. The record identifies the study as single-blind but does not state who was masked.

The population was healthy male participants, and the intervention was a single oral dose under the described fasting conditions. The results cannot be extended from this record to repeated administration or other populations. Numerical results for the listed pharmacokinetic secondary outcomes and the described pharmacodynamic objectives are not reported in the registry record. These limitations restrict interpretation to the posted short-term safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: This Study in Healthy Men Tests How Different Doses of BI 1323495 Are Taken up in the Body and How Well They Are Tolerated. — NCT03588390.
• Registry record last updated 2024-02-22; status last verified 2023-07.
• Results first posted 2024-02-22.
• 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

NCT03588390 is a completed phase 1 study sponsored by Boehringer Ingelheim. The registry records randomized allocation, single masking, a parallel-group design, and enrollment of 63. The study began on 2018-07-31, with primary completion on 2018-11-14.

The primary outcome was the percentage of treated participants with drug-related adverse events from administration until the end of the trial, up to 15 days. Posted percentages were 6.7% for placebo and 50.0%, 33.3%, 0.0%, 16.7%, 0.0%, 16.7%, 50.0%, and 16.7% for BI 1323495 Dose Groups 1 through 8. The serious-adverse-event summary reports 0 serious events and 0 deaths in each listed group.

The record lists plasma AUC0-∞ and Cmax as secondary outcomes, but numerical results for them are not reported. Dose amounts, confidence intervals, inferential comparisons, and several analysis details are also not reported in the registry record.