Single Rising Dose Trial of BI 425809 for Healthy Japanese and Chinese Male Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Single Rising Dose Trial of BI 425809 for Healthy Japanese and Chinese Male Subjects (NCT02383888), a randomized phase 1 study. The primary outcome is Number of Subjects With Drug-Related Adverse Events (AEs).

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, parallel-group Phase 1 trial. The registry title describes a single rising dose study of BI 425809 in healthy Japanese and Chinese male subjects, and the official title specifies a randomized, double-blind, placebo-controlled design within dose groups. The registry record lists 49 enrolled participants and a completed status.

The study began on 2015-05-11, with primary completion on 2015-08-06. Participants received placebo or one of three single oral doses: BI 425809 10 mg, 25 mg, or 50 mg. The active-dose descriptions specify administration with 240 mL of water after an overnight fast of at least 10 hours. Placebo was also taken with 240 mL of water after an overnight fast of at least 10 hours.

The primary endpoint was the number of subjects with drug-related adverse events up to 11 days after drug administration. The registry also lists pharmacokinetic outcomes: maximum measured plasma concentration, area under the concentration-time curve to infinity, area under the concentration-time curve to the last quantifiable time, time to maximum concentration, and half-life. The registry record does not report further details about the randomization procedure, the blinding procedures, dose-escalation decisions, or the criteria used to attribute an adverse event to study drug.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Treated Set (TS): This analysis set included all subjects who received the study 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): This analysis set included all subjects who received the study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Drug-Related Adverse Events (AEs), measured over Up to 11 days after drug administration..

The primary endpoint counts participants with drug-related adverse events up to 11 days after drug administration. It is a participant-level count: a participant is counted as having the outcome if a drug-related adverse event was recorded during the stated timeframe. The outcome description identifies the measure as the number of subjects with drug-related adverse events, and the analysis population is the Treated Set, consisting of all subjects who received study drug.

Safety and tolerability are central questions in a trial of single rising doses, and adverse-event monitoring provides a way to describe unwanted events observed after dosing. A participant count focuses on whether each person experienced an event, rather than how many separate events occurred in that person. The registry outcome does not provide event-level detail or severity grading for this primary measure. Nor does the count alone establish whether an event was caused by treatment; the registry labels the outcome as drug-related but does not report the attribution process.

The measure should be interpreted alongside the time window and the small group sizes. It describes reported drug-related events up to 11 days after administration, not all possible safety outcomes or longer-term experience. Pharmacokinetic measures are listed separately as secondary outcomes and address drug concentration over time, rather than the primary adverse-event count.

7. Results Posted in the Registry

• BI 425809 10 mg Tablet: 0.0% (0/12) versus 7.7% (1/13) on control; risk difference -7.7 percentage points (95% CI -22.2 to 6.8); unadjusted two-proportion z-test p = 0.327.
• BI 425809 25 mg Tablet: 0.0% (0/12) versus 7.7% (1/13) on control; risk difference -7.7 percentage points (95% CI -22.2 to 6.8); unadjusted two-proportion z-test p = 0.327.
• BI 425809 50 mg Tablet: 0.0% (0/12) versus 7.7% (1/13) on control; risk difference -7.7 percentage points (95% CI -22.2 to 6.8); unadjusted two-proportion z-test p = 0.327.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a binary participant outcome: each treated participant either had at least one drug-related adverse event during the stated period or did not. For each group, the registry reports the number of participants with the outcome and the number in the analysis group. The comparison is expressed as a risk difference, which is the active-group event proportion minus the placebo-group event proportion. The posted risk difference is -0.077 for each active dose compared with placebo.

What does a risk difference describe?

In general, a risk difference puts two event proportions on an additive scale. A value of zero corresponds to equal observed proportions; negative values indicate a lower observed proportion in the active group than in the reference group, and positive values indicate a higher observed proportion. This is a description of the contrast, not a measure of the number of events prevented or caused in a broader population. In this trial, the actual participant counts are particularly important: placebo had 1 of 13 participants with the outcome, while each active-dose group had 0 of 12.

How should the p-value be read?

Each comparison has an unadjusted p-value of 0.327. In general, a p-value assesses how compatible the observed data are with a specified null model, under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The registry record does not report the test used to obtain these p-values, so the calculation and its assumptions cannot be evaluated from the record alone. Because the p-values are unadjusted, they do not reflect a reported correction for examining multiple dose comparisons.

What information does the confidence interval add?

The posted 95% confidence interval for every risk difference runs from -0.222 to 0.068. In general, a confidence interval shows a range of effect values compatible with the data under the method used to construct it. Its width conveys precision: wider intervals indicate less precise estimates. Here, the interval covers zero and includes both negative and positive values. It therefore does not isolate the direction of the underlying difference. The interval also allows a range of contrasts that is broad relative to the point estimate, consistent with the sparse event counts and small group sizes. The registry does not identify the confidence-interval method.

Why do sparse counts matter?

When an endpoint is uncommon, a small number of observed participants can determine the estimate. Zero observed events in a group does not mean the underlying event probability is zero; it means no participant in that group was recorded with the endpoint over the defined observation period. Sparse data can make standard approximations less dependable, depending on the method, and can produce substantial uncertainty. The record does not provide enough methodological detail to assess whether an exact or approximate method was used.

The registry describes three separate active-dose comparisons against placebo. Because the same placebo group is used in each comparison, the comparisons are not independent of one another. In general, multiple comparisons can increase the chance of at least one apparently notable result if each is judged separately. The record does not report a multiplicity strategy, a prespecified hierarchy, or a primary dose comparison; consequently, the unadjusted p-values should not be treated as a familywise error-controlled analysis.

The trial also lists pharmacokinetic outcomes, including plasma maximum concentration and several area-under-the-curve measures, but their numerical results are not reported in the registry record. The record does not report the statistical analysis plan, the method used for missing outcome data, or a sample-size justification. No inference about the adequacy of the original design or the planned power is possible from the available primary outcome results. Any planning illustrations based on observed effects are design examples, not observed power and not evidence that the trial was planned to detect a particular difference.

10. Confidence Intervals and Precision

Each active-dose comparison has the same estimated risk difference versus placebo: -0.077. The 95% confidence interval is -0.222 to 0.068 for the 10 mg group, the 25 mg group, and the 50 mg group. These intervals cross zero, so the posted estimates are compatible with differences in either direction under the method used. They do not provide a precise determination of whether the true group contrast is negative, zero, or positive.

In general, a confidence interval represents uncertainty around an estimated effect. Its width is an important part of the result: a point estimate alone can make a comparison look more definite than the data allow. The interval is wide in relation to the small observed counts, and the observed proportions are based on only 13 participants in placebo and 12 participants in each active-dose group. With an uncommon outcome, each observed participant can have considerable influence on an estimate.

The registry record does not report the confidence-interval construction method, so the interval's assumptions cannot be checked from the posted information. The record also does not report a prespecified precision target for the primary endpoint. These estimates should therefore be read as descriptive, imprecise comparisons of the observed event proportions, rather than as proof of equivalence or evidence that rare events are excluded. The similar posted values across doses reflect the same observed counts in each active group and placebo, not proof that dose groups have identical underlying risks.

11. Multiplicity, Missing Data and Analysis Populations

The registry reports an unadjusted p-value for each of the three dose comparisons with placebo. It does not report a multiplicity adjustment, a testing hierarchy, or a strategy for interpreting the set of comparisons together. In general, when several comparisons are tested, evaluating each p-value separately can make the overall chance of a false-positive result higher than for a single test. Since every posted p-value is 0.327, none is small, but the absence of a stated adjustment remains relevant to understanding the analysis plan and its error control.

The registry identifies the primary analysis population as the Treated Set: all subjects who received study drug. This is the population underlying the primary outcome counts. The record does not report whether any randomized participants were excluded from this set, how participants were assigned to dose groups for analysis, or whether any additional analysis populations were used.

The registry record does not report how missing adverse-event information was handled, whether any participants had incomplete follow-up, or whether outcome data were imputed. It also does not report a statistical analysis plan, a sample-size justification, planned interim analyses, or a prespecified approach to the three active-dose comparisons. These details should not be inferred from the trial's randomized, double-blind design or from its posted estimates.

There are pharmacokinetic measures listed as secondary outcomes, but their numerical results are not reported in the registry record. The record does not report how multiplicity across the primary endpoint and secondary outcomes was managed. As a result, the primary safety comparison can be described from the posted counts and unadjusted estimates, while the broader analysis strategy and treatment of missing data remain unclear.

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 non-serious adverse event terms

The serious adverse event counts are zero in all four groups: 0 of 13 participants in placebo, 0 of 12 in BI 425809 10 mg, 0 of 12 in BI 425809 25 mg, and 0 of 12 in BI 425809 50 mg. The registry lists no serious adverse event terms. These figures mean that no serious adverse events were recorded for the listed groups in the registry results; they do not establish that serious events cannot occur.

The adverse-event record also reports other, non-serious adverse events affecting 1 of 13 participants in placebo, 1 of 12 in the 10 mg group, 0 of 12 in the 25 mg group, and 2 of 12 in the 50 mg group. These counts are separate from the serious adverse event counts and should not be conflated with the primary drug-related adverse-event endpoint, even though that endpoint also reports participant counts. The registry does not provide terms or further details for these other events in the information available.

Deaths are not reported in the registry record. Group-level safety counts in a trial of this size and duration describe observed events only; they cannot rule out uncommon events or events occurring beyond the stated follow-up.

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

The primary results describe a small number of drug-related adverse events during follow-up: 1 of 13 participants in placebo and 0 of 12 participants in each BI 425809 dose group. The estimated risk difference was -0.077 for each active dose compared with placebo, and each 95% confidence interval ranged from -0.222 to 0.068. The unadjusted p-value was 0.327 in each comparison. Together, the counts and intervals show that the observed data are limited and do not precisely distinguish the group risks.

These findings do not establish that BI 425809 reduces, increases, or leaves unchanged the probability of a drug-related adverse event. A zero count in a dose group is an observation from the participants studied, not evidence that the event risk is absent. Likewise, a confidence interval crossing zero does not demonstrate equivalence. The posted results also do not establish safety for other populations, longer exposure, repeated dosing, or other treatment settings. The trial involved healthy Japanese and Chinese male subjects receiving single doses, and its primary adverse-event timeframe was up to 11 days after drug administration.

The registry describes the trial as evaluating safety, tolerability, and pharmacokinetics, and lists pharmacokinetic measures as secondary outcomes. Numerical pharmacokinetic results are not reported in the registry record, so those outcomes cannot be interpreted from this record. The primary adverse-event comparison should not be used to infer pharmacokinetic behavior or dose proportionality.

The appropriate statistical reading is therefore narrow: the posted counts show few drug-related events, with one in placebo and none in the three active-dose groups, while the estimated differences are imprecise. Serious adverse events were recorded as zero in all groups, but the trial's group sizes and follow-up do not establish the absence of uncommon or later events. These results characterize the registry record for this trial, not a general guarantee about the treatment.

14. Why This Trial Matters Statistically

This trial illustrates why counts and uncertainty must be read together. The observed primary outcome counts are zero in each active-dose group and one in placebo, but the effect estimates have confidence intervals that extend on both sides of zero. Looking only at the direction of the point estimate would overstate what the sparse data can establish. Looking only at the p-value would also omit the size and uncertainty of the estimated contrast.

The trial includes three active doses and a shared placebo group. This structure allows separate dose-versus-placebo descriptions, but each comparison is based on small groups and the same single placebo event. The registry reports identical estimates for all three comparisons because the recorded participant counts are the same across active groups and placebo. That pattern is descriptive and does not establish that underlying risks are equal across doses.

It also illustrates the distinction between a safety endpoint and pharmacokinetic objectives. The primary count addresses participants with drug-related adverse events over the stated period, while the secondary outcomes concern plasma concentrations and concentration-time measures. The registry lists those measures but does not report their numerical results, so the available safety counts cannot answer the pharmacokinetic questions.

Finally, this record shows the value of reporting analysis details alongside results. The design is identified as randomized, double-blind, and parallel, and the Treated Set is described. However, the statistical test, confidence-interval method, missing-data handling, sample-size rationale, and multiplicity plan are not reported in the registry record. Those omissions limit how fully the precision and analysis assumptions can be assessed. The estimates remain interpretable as posted comparisons, but methodological uncertainty should remain part of their statistical context.

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 few observed participants with drug-related adverse events: 1 of 13 in placebo and 0 of 12 in each active-dose group. This makes the estimated comparisons sensitive to individual observations and limits precision. The confidence intervals are broad and include zero, so the results do not resolve the direction or magnitude of the underlying group differences.

The endpoint covers drug-related adverse events up to 11 days after drug administration. It does not describe longer-term safety, repeated administration, or experience outside the healthy Japanese and Chinese male population enrolled. The trial used single doses of 10 mg, 25 mg, and 50 mg, so these findings should not be generalized beyond the studied population, dosing conditions, and follow-up without further evidence.

The record does not report the method used to identify or attribute drug-related events, the statistical test, the confidence-interval method, or handling of missing safety information. It also does not report a sample-size justification, an interim-analysis plan, or a multiplicity strategy. These gaps limit evaluation of the analysis assumptions and the design's ability to estimate uncommon events. Numerical results for the listed pharmacokinetic outcomes are not reported in the registry record, which prevents assessment of those trial objectives from the results described.

Finally, the registry reports no serious adverse events in the groups, but absence of recorded events in these small groups is not evidence that rare serious events are impossible. Deaths are not reported in the registry record. These are limitations of what can be concluded from the posted results, rather than proof that additional information was not collected.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Single Rising Dose Trial of BI 425809 for Healthy Japanese and Chinese Male Subjects — NCT02383888.
• Registry record last updated 2026-03-30; status last verified 2026-02.
• Results first posted 2026-03-30.
• 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

NCT02383888 is a completed, randomized, double-blind, parallel-group Phase 1 trial of single rising oral doses of BI 425809 in healthy Japanese and Chinese male subjects. The registry reports 49 enrolled participants and primary completion on 2015-08-06. The primary endpoint counted participants with drug-related adverse events up to 11 days after drug administration, using the Treated Set.

The primary outcome occurred in 1 of 13 placebo participants and 0 of 12 participants in each BI 425809 dose group: 10 mg, 25 mg, and 50 mg. Each active-versus-placebo risk difference was -0.077, with a 95% confidence interval from -0.222 to 0.068 and an unadjusted p-value of 0.327. Serious adverse event counts were zero in all groups. The registry lists pharmacokinetic secondary outcomes, but their numerical results are not reported in the registry record.