This Study is Done in Healthy Japanese Volunteers. It Looks at How Different Doses of BI 1015550 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 is Done in Healthy Japanese Volunteers. It Looks at How Different Doses of BI 1015550 Are Taken up in the Body and How Well They Are Tolerated. (NCT03542344), a randomized phase 1 study. The primary outcome is Number of Participants With Drug-related Adverse Events.

2. Clinical Question

3. Trial Design

This was a completed Phase 1, randomized, double-blind, placebo-controlled, parallel-group study. Its official title describes safety, tolerability, and pharmacokinetics after single rising oral doses of BI 1015550 in healthy Japanese male subjects. The registry records an enrollment of 16 and lists a start date of 2018-06-04 and a primary completion date of 2018-08-24. Those dates describe the registry timeline; they do not establish when each participant was assessed.

The outcome record lists placebo, BI 1015550 12mg, and BI 1015550 24mg arms. The number of participants in the posted outcome groups is 4 for placebo, 6 for BI 1015550 12mg, and 6 for BI 1015550 24mg. The intervention list separately names BI 1015550 6 mg, while the arm descriptions list 12mg and 24mg and provide no text about the arms. The record does not explain this difference. It is therefore safest to describe the reported outcome groups as listed, rather than infer how the dose levels were assigned or administered.

The primary objective was to investigate safety and tolerability after single rising doses. The stated secondary objectives concerned pharmacokinetics, including dose proportionality after single dosing. The registry lists AUC0-inf and Cmax as secondary outcomes. It does not report detailed dose escalation procedures, visit schedules, randomization methods, masking procedures, or the pharmacokinetic results.

The registry marks the study completed. Completion does not by itself imply that every planned outcome was posted, or that results from this small volunteer study apply to other populations or treatment settings. The record does not report a rationale for the enrollment target or a detailed protocol description.

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 to participants in the trial. Subjects attended specialist sites which would then ensure that they met all strictly implemented inclusion/exclusion criteria. Subjects were not to be assigned to treatment groups if any one of the specific entry criteria were violated.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Treated set (TS): This subject set included data from all subjects who received at least 1 dose of 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): This subject set included data from all subjects who received at least 1 dose of trial drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Drug-related Adverse Events, measured over From drug administration until end of study, up to 9 days.

The primary endpoint is the number of participants with drug-related adverse events. It is a count of participants, rather than a count of every event experienced. The registry says that the number is presented and defines the relevant population as the treated set: participants who received at least one dose of trial drug.

The specified observation period begins at drug administration and continues until the end of the study, up to 9 days. This endpoint is used to describe whether participants experienced events judged to be related to the study drug during the stated period. In general, safety endpoints help characterize the kinds of events observed and how frequently participants are affected. A participant count does not convey event severity, duration, recurrence, or clinical course on its own.

The posted primary endpoint value is 0 in the placebo group, 0 in the BI 1015550 12mg group, and 0 in the BI 1015550 24mg group. These are the reported counts of participants with drug-related adverse events, not proof that no adverse events of any kind occurred. The registry separately reports one other adverse event in the placebo group and none in the BI 1015550 groups. Serious adverse events are listed separately, with zero reported in each group.

The endpoint is limited to the specified treated set and observation window. The registry record does not report how drug relatedness was assessed, which event-coding system was used, or additional detail about adverse-event collection. Those omissions limit how fully the endpoint can be interpreted.

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 with at least one drug-related adverse event, rather than a total count of all events. This distinction matters because one participant may experience more than one event, while the endpoint still counts that participant once. The posted values are 0 for placebo, 0 for BI 1015550 12mg, and 0 for BI 1015550 24mg. The registry identifies the treated set as the population for this outcome, including participants who received at least one dose of trial drug.

As a general statistical principle, binary outcomes record whether a participant met a condition or did not. Counts can be described alongside the number of participants assessed in each group, but a count alone is not a complete estimate of an event rate. The registry posts group sizes of 4, 6, and 6 for placebo, BI 1015550 12mg, and BI 1015550 24mg, respectively. Because the outcome counts are zero, those observed data do not show a drug-related event in these groups during the stated period. They do not establish that the event probability is zero outside the observed participants.

Why is uncertainty important when counts are zero?

In general, statistical uncertainty reflects how much the observed data constrain an underlying quantity, such as an event probability. Sparse data provide limited information. A zero count can occur even when the underlying probability is above zero, particularly when the number of observed participants is limited. This is why a zero count should be read as an observation, not as proof that an event cannot occur.

A confidence interval is a statistical range constructed to convey uncertainty around an estimate under stated assumptions. For a binary outcome, an interval for an event probability or a between-group contrast can help show how much uncertainty remains. No such interval for the primary endpoint is reported in the registry record. The record also does not provide a numerical effect estimate or a completed statistical comparison for this endpoint. It states that values were missing or not estimable for a two-arm comparison. Accordingly, there is no posted inferential estimate to interpret as evidence of a group difference or equivalence.

What do the study design labels contribute?

Randomization is generally intended to reduce systematic differences between groups by using an allocation process that is not based on participant characteristics. Double masking is generally intended to limit knowledge of group assignment during aspects of trial conduct and assessment. A parallel-group design assigns participants to a group that is compared with other groups rather than having each participant receive all conditions. These are general descriptions of design terms. The registry records the study as randomized, double-blind, and parallel group, but procedural details about sequence generation, concealment, and maintenance of masking are not reported in the registry record.

These design labels do not replace a detailed assessment of implementation. The record does not explain whether any masking was broken, how adverse events were judged to be drug-related, or how missing observations were handled. Those details can affect the interpretation of results, especially when the outcome depends partly on assessment and attribution.

How should the planning assumptions be understood?

In general, sample-size planning uses assumptions about the effect to be detected, the significance level, allocation, and statistical method. A planning illustration describes what might be required under those assumptions; it does not describe the number of participants actually observed, and it is not observed power. The registry’s stated planning assumptions refer to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect specified as a fraction of the observed effect. For non-time-to-event outcomes, the described output is participants per arm for 80% power or 90% power.

The record does not report the trial’s own sample-size justification or its detailed design assumptions. The observed primary outcome is zero in every reported group, so it does not provide a nonzero observed difference on which to base an effect-size illustration. Any planning illustration should therefore be understood only as a hypothetical calculation under its stated assumptions, not as evidence that the study had a particular power to detect a safety effect. The record does not report numerical planning estimates alongside the registry entries.

What can be inferred from absent analysis results?

General statistical practice distinguishes descriptive summaries from formal comparisons. A descriptive count tells what was observed in each group. A formal comparison estimates a contrast and may include an uncertainty interval or a test under specified assumptions. The registry lists no analysis entries, and it does not post a primary-endpoint comparison. The reader should not infer that a test was performed, that a prespecified analysis supported a particular conclusion, or that the groups were statistically equivalent.

For sparse binary outcomes, some standard approximations may be unreliable or not estimable, especially when counts are zero. More appropriate methods depend on the planned estimand, analysis population, and study design. This is a general methodological point, not a claim about an unreported analysis in this trial. The registry does not report the statistical analysis plan, the test-selection rationale, or an alternative method for the primary endpoint.

The listed secondary outcomes concern AUC0-inf and Cmax, and the stated secondary objectives include dose proportionality. Those outcomes require pharmacokinetic measurements and their own analysis methods. Their results, analysis populations, and statistical methods are not reported in the registry record. The safety counts cannot substitute for those missing pharmacokinetic results.

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 1015550 12mg", "BI 1015550 24mg")
n      <- c(4, 6, 6)
events <- c(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  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  BI 1015550 12mg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  BI 1015550 24mg  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 identifies one primary outcome, the number of participants with drug-related adverse events, and lists AUC0-inf and Cmax as secondary outcomes. Testing or interpreting multiple outcomes can raise a multiplicity issue: in general, considering several statistical tests can increase the chance of an apparently notable finding unless the analysis plan addresses that possibility. The registry record does not report whether any multiplicity adjustment was planned or used, or how the secondary outcomes were to be prioritized. No secondary outcome results are posted in the record.

The record defines the primary safety population as the treated set, comprising participants who received at least one dose of trial drug. It does not report a separate intention-to-treat population, a per-protocol population, or how those populations would be used in analyses. It also does not report a detailed analysis plan or whether the posted counts include every participant in the defined set for every outcome.

Missing-data handling is not reported in the registry record. The record does not describe whether there were missing adverse-event assessments, how any incomplete observations were treated, or whether participants with incomplete follow-up were included in an analysis. The specified primary-outcome timeframe extends from administration until the end of study, up to 9 days, but the record does not provide participant-level follow-up details.

These omissions do not show that data were missing or that analyses were inappropriate. They mean the registry record does not provide enough information to assess missingness, multiplicity control, or the full analysis-population strategy. The posted counts should therefore be read as the recorded summaries, without assuming unreported procedures.

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 zero serious adverse events in the placebo group, zero in the BI 1015550 12mg group, and zero in the BI 1015550 24mg group. The adverse-event information lists 4 participants at risk in the placebo group and 6 in each BI 1015550 group; the count affected by serious adverse events is zero in every group. No deaths are reported in these groups.

These serious-event counts are separate from the primary endpoint, which counts participants with drug-related adverse events. A serious event is not the same thing as any adverse event, and the posted zero serious-event counts do not mean that no other events occurred. The record lists one participant with an other adverse event in the placebo group and none in the BI 1015550 groups. The registry does not give event terms or details that would explain the event or its relationship to the primary endpoint.

In general, safety counts describe what was observed among the participants followed during a defined period. A zero count in a small group does not establish that serious events cannot occur, nor does it quantify their likelihood beyond the observed study. The observation period for the primary outcome is from drug administration until the end of study, up to 9 days. The registry record does not report further follow-up or additional safety analyses. These figures should be read as descriptive reports for the stated groups and period, not as a complete characterization of safety.

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

The result establishes a narrow descriptive fact: the registry reports zero participants with drug-related adverse events in each of the placebo, BI 1015550 12mg, and BI 1015550 24mg groups during the specified period. It also reports zero serious adverse events in each group. The other adverse-event count is one in the placebo group and zero in each BI 1015550 group. These counts are limited to the study’s recorded participants and outcome definitions.

The result does not establish that BI 1015550 has no adverse effects, that the groups have identical risks, or that the treatments are equivalent. Zero observed events are not proof of zero underlying risk. The registry does not report an estimated group contrast, uncertainty interval, or statistical test for the primary endpoint. It specifically notes that values for a two-arm comparison were missing or not estimable. Without an inferential estimate, the observed counts cannot support a quantified comparison.

The study was conducted in healthy Japanese male subjects and is recorded as a Phase 1 trial of single rising oral doses. The registry does not report evidence that would establish whether results apply to other populations, repeated dosing, longer treatment, or settings beyond the study. Generalization requires evidence relevant to those populations and conditions; these safety counts alone do not supply it.

The stated secondary objectives concern pharmacokinetics, including dose proportionality, and the registry names AUC0-inf and Cmax as secondary outcomes. Their results are not posted in the registry record. Thus, the safety counts cannot answer questions about drug exposure, concentration, or proportionality across doses.

In general, interpretation depends on the endpoint definition, the population assessed, the follow-up period, and the uncertainty around estimates. The record reports the treated-set definition and a safety observation period of up to 9 days, but it does not report a detailed statistical plan, handling of missing data, or further follow-up. The appropriate conclusion is limited to what was recorded for these groups over this period, without claiming either absence of risk or a confirmed difference between groups.

14. Why This Trial Matters Statistically

This trial illustrates a basic statistical challenge in early safety studies: event counts can be informative descriptively while remaining imprecise for estimating uncommon risks. The primary outcome has a count of zero in each reported group. That is a clear description of the observed data, but small groups provide limited information about events that were not observed. A zero count is therefore not equivalent to evidence that the underlying event probability is zero.

The study also shows why endpoint definitions matter. The primary measure counts participants with drug-related adverse events, while the registry separately reports serious and other adverse-event counts. These categories address related but distinct questions. Treating them as interchangeable could misrepresent what was actually measured. The stated period, from drug administration until the end of study, up to 9 days, also sets a boundary on what the count can describe.

The registry records randomized, double-blind, placebo-controlled, parallel-group methods, but the record does not provide the detailed procedures or an inferential comparison for the binary endpoint. This highlights the difference between a design label and the information needed to evaluate implementation and analysis. A result can be reported by group without providing a formal estimate of the contrast or its uncertainty.

Finally, the study’s objectives include pharmacokinetics, but the posted outcome record does not include results for AUC0-inf or Cmax. Separating outcomes that are listed from outcomes with reported results is important when assessing what a registry entry can support. The record is useful for identifying the study question, design, and observed safety counts, while leaving important details and results unreported.

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 group sizes are limited: the registry reports 4 participants in the placebo group, 6 in the BI 1015550 12mg group, and 6 in the BI 1015550 24mg group. With zero drug-related adverse events recorded in each group, the data offer little ability to characterize uncommon events or estimate differences precisely. The registry does not report confidence intervals or another uncertainty measure for the primary outcome.

The registry entries do not fully align on dose labeling. The intervention list names BI 1015550 6 mg, while the outcome arms and arm descriptions name BI 1015550 12mg and BI 1015550 24mg. The record does not explain this discrepancy, so the listed outcome groups should not be used to infer details about dose assignment beyond their labels.

The primary endpoint depends on classifying an event as drug-related, but the registry does not report the attribution process, event terms, or adjudication procedures. It also does not report participant-level follow-up, missing-data handling, a detailed statistical analysis plan, or the method used for any formal comparison. The record indicates that a two-arm binary comparison was not estimable or had missing values, and no analysis entries are listed.

Although pharmacokinetic outcomes and dose proportionality are part of the stated objectives, results for AUC0-inf and Cmax are not reported in the registry record. The record also does not provide the trial’s sample-size justification, detailed eligibility criteria, or follow-up beyond the specified primary safety timeframe. These limitations restrict interpretation to the posted descriptive counts and study details.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: This Study is Done in Healthy Japanese Volunteers. It Looks at How Different Doses of BI 1015550 Are Taken up in the Body and How Well They Are Tolerated. — NCT03542344.
• Registry record last updated 2025-11-28; status last verified 2025-10.
• Results first posted 2025-11-28.
• 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 records NCT03542344 as a completed Phase 1, randomized, double-blind, placebo-controlled, parallel-group study of single rising oral doses of BI 1015550 in healthy Japanese male subjects. Its stated primary objective was to investigate safety and tolerability; secondary objectives concerned pharmacokinetics, including dose proportionality. The recorded enrollment is 16, with a start date of 2018-06-04 and a primary completion date of 2018-08-24.

The primary outcome is the number of treated participants with drug-related adverse events from administration until the end of study, up to 9 days. The posted count is zero for placebo, BI 1015550 12mg, and BI 1015550 24mg. Serious adverse-event counts are also zero in each group. The registry lists AUC0-inf and Cmax as secondary outcomes but does not report their results. It does not report a formal primary-endpoint comparison, an uncertainty interval, detailed missing-data methods, or the statistical analysis plan.