A Study to Test How Different Doses of Nerandomilast (BI 1015550) Are Taken up in the Body of Healthy Japanese Men: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Test How Different Doses of Nerandomilast (BI 1015550) Are Taken up in the Body of Healthy Japanese Men (NCT06139302), a non-randomized phase 1 study. The primary outcome is Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf).

2. Clinical Question

3. Trial Design

This was a completed Phase 1, open-label, non-randomized, parallel-group study. Its stated purpose was to investigate the pharmacokinetics of R-BI 1015550 in healthy Japanese male participants after oral administration of two different single doses of BI 1015550. Nerandomilast was the listed drug intervention. The trial record lists 12 participants enrolled and gives the status as completed.

The two described groups received a single film-coated tablet of nerandomilast Formulation C1: 9 mg or 18 mg. Each dose was taken orally with 240 milliliters of water after an overnight fast of at least 10 hours. The registry records 6 participants at risk for serious adverse events in each group. The safety counts do not, by themselves, establish the number included in the primary pharmacokinetic analysis.

In a parallel-group design, participants receive a dose assigned to their group rather than each participant necessarily receiving both doses. The record does not describe a crossover or within-participant dose comparison. Allocation was non-randomized, and masking was absent; participants and study personnel therefore were not blinded according to the listed design. The method used to assign participants to dose groups is not reported in the registry record.

Blood sampling for the primary pharmacokinetic measure was scheduled within 3 hours before drug intake and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hours after drug intake. The completed status indicates that the trial is no longer listed as ongoing, but does not establish that every planned measurement was available for every participant. Actual completion of sampling, participant disposition, and analysis-set counts are not reported in the registry record.

The record does not report a placebo group, a randomized allocation procedure, or a masking procedure. This was a pharmacokinetic study in healthy participants, not a trial designed to estimate a clinical treatment effect in people with a disease. The registry does not report a protocol-based rationale for selecting the doses or a sample-size justification.

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: Pharmacokinetic (PK) parameter analysis set (PKS): The PKS set included all subjects in the treated set (TS) who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a subject was included in the PKS, even if he contributed only one PK parameter value for one period to the statistical assessment.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Treated set (TS): The treated set included all subjects who were treated with at least one dose of trial drug. The treatment assignments were determined based on the first treatment the subjects received. The treated set was used for safety analyses.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf), measured over Within 3 hours (hrs) before drug intake and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 and 144 hrs after drug intake..

The primary endpoint was the area under the nerandomilast plasma concentration-time curve from 0 extrapolated to infinity, abbreviated AUC0-inf in the registry record. It is expressed in hours*nanomoles/Liter. In general, the area under a concentration-time curve represents cumulative systemic exposure over the measured period. Extending the estimate to infinity adds an extrapolated contribution beyond the last observed concentration, so the result depends both on observed samples and on the method used to characterize the later concentration decline.

Pharmacokinetic endpoints are used to describe drug exposure after administration. For this trial, comparing the endpoint across the 9 mg and 18 mg groups could help characterize exposure at the two studied doses. That comparison is descriptive in this non-randomized design and should not be treated as a randomized estimate of a causal dose effect.

The registry specifies the endpoint as a geometric mean with geometric coefficient of variation as the dispersion measure. A geometric mean is a way to summarize positive measurements on a multiplicative scale; the geometric coefficient of variation describes relative variability on that scale. These summaries differ from an arithmetic mean and standard deviation, and should be interpreted according to their stated scale.

The registry gives the endpoint definition and sampling schedule, but the group-specific geometric means and geometric coefficients of variation are not reported in the registry record. The endpoint’s numerical results, any comparison between doses, and the precision of those results therefore cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial’s primary endpoint is a pharmacokinetic summary rather than a clinical outcome. Concentration-time sampling records the amount of drug measured in plasma at scheduled times after administration. AUC0-inf combines information across that curve and extends the estimate beyond the final observed concentration to infinity. In general, this endpoint is used to summarize overall exposure rather than the concentration at any single time. Its interpretation depends on the observed concentration profile and the extrapolation beyond the observation period.

What does a geometric mean describe?

The registry says that AUC0-inf is reported as a geometric mean, with geometric coefficient of variation as the dispersion measure. In general, a geometric mean summarizes positive values on a multiplicative scale. This can be useful for measurements that vary proportionally, where a relative change may be more meaningful than an additive change. The geometric coefficient of variation describes relative spread around the geometric mean. It is not an absolute difference in the endpoint’s units, and it should not be read as if it were a standard deviation.

The record does not report the numerical geometric mean or geometric coefficient of variation for either group. It also does not give confidence intervals or a test of the between-group difference. Consequently, the stated summary method can be explained, but the numerical estimates and their uncertainty cannot be evaluated from the registry record.

How should the sampling schedule be understood?

The registry lists sampling within 3 hours before dosing and at multiple times after dosing, extending to 144 hours. A schedule with measurements across the concentration-time profile can inform the observed portion of an exposure estimate and its later extrapolation. The listed times are planned measurement times; they do not establish that every sample was collected or usable. The record does not report participant-level concentration data, the number of evaluable samples, or the method used to estimate the extrapolated tail of AUC0-inf.

What does the design allow the comparison to say?

The study used non-randomized allocation and a parallel-group structure. In general, randomization helps balance measured and unmeasured baseline factors across groups, while non-random allocation does not guarantee that balance. A parallel design compares the outcomes of different groups rather than necessarily comparing multiple doses within the same participant. In this trial, the registry does not say how the dose groups were formed or whether any baseline adjustment was used. A difference between group summaries, if reported, would therefore be descriptive and potentially influenced by group differences other than dose.

The study was also open-label. This means masking was not part of the listed design. Pharmacokinetic concentrations are laboratory measurements, but open-label status still matters when considering study conduct and the possibility of differences in procedures, reporting, or handling. The registry does not describe laboratory blinding or additional safeguards, so none can be assumed.

What can a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and the statistical method, expressing uncertainty around an estimate. It does not guarantee that the true value lies within a particular interval, nor does it replace an assessment of design limitations. No confidence interval for the primary endpoint is reported in the registry record. There is therefore no reported interval from which to assess the statistical precision of the group estimates.

What does over-dispersion mean in general?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model understates variability, standard errors and uncertainty intervals can be too narrow, and statistical tests can appear more decisive than warranted. This concept is relevant when evaluating whether a model fits the data, but the registry record does not report an analysis model for the primary endpoint or any assessment of over-dispersion. It would be inappropriate to infer that a particular model or diagnostic was used.

What do the planning illustrations represent?

The record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a fraction of the observed effect; for time-to-event settings, the planning quantity is total events, while other illustrations use participants per arm for 80% power or another stated power level. These are planning calculations, not observed power and not evidence that the trial was designed around those assumptions. The specific planning estimates and effect fractions are not reported in the registry record. The record also does not report the trial’s own sample-size justification.

For a small pharmacokinetic study, a planning calculation based on an observed effect is best understood as a hypothetical design illustration: it asks what sample size might correspond to assumptions about an effect and a statistical method. It does not change the number enrolled, establish that the study had adequate precision, or demonstrate that a comparison is statistically conclusive. The record’s enrollment and safety counts do not substitute for endpoint-specific precision estimates.

Finally, the registry lists 0 analyses. This means that no analysis entries are recorded in the registry information; it does not identify which statistical procedures may have been used outside those entries. The analysis model, any transformations beyond the stated geometric summary, adjustment methods, hypothesis tests, and confidence-interval procedures are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan describing multiplicity control. It identifies a primary endpoint and indicates that the trial had 2 outcome measures, but the other outcome’s definition and analysis details are not reported in the registry record. Without the full set of outcomes, their planned testing order, and the intended inferential procedures, it is not possible to determine whether multiple comparisons were planned or how their interpretation was to be handled.

The record lists 0 analyses. It does not report whether any interim analyses were planned or conducted, and no interim-analysis procedure should be inferred. The sample-size illustrations described in the record are planning illustrations based on an observed effect, not a substitute for a prospectively documented sample-size justification or analysis plan.

The primary pharmacokinetic analysis population is described as treated participants who provided at least one pharmacokinetic endpoint that was not excluded because of a relevant protocol deviation or pharmacokinetic non-evaluability. This definition gives a rule for inclusion, but the number of participants meeting it is not reported in the registry record. The record does not report the number of missing measurements, reasons for missingness, exclusions, or methods for handling missing endpoint data.

In general, missing pharmacokinetic measurements can affect the precision and, depending on their pattern and handling, the estimated exposure. A stated analysis-population definition does not reveal whether missingness was related to participant characteristics, dose group, or measured concentrations. The registry record does not provide enough information to assess those possibilities, reconstruct the analysis set, or evaluate sensitivity to missing data.

11. 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 serious adverse event counts for participants at risk in each dose group. In the 9 mg group, 0 of 6 participants at risk had a serious adverse event; in the 18 mg group, 0 of 6 had a serious adverse event. The record lists 0 deaths in both groups. For other adverse events, it records 1 of 6 participants affected in the 9 mg group and 0 of 6 in the 18 mg group.

These are counts, not a complete description of the events. The registry does not report the non-serious event term, its severity, timing, duration, outcome, or whether it was considered related to treatment. It lists no top serious adverse event terms because there were no serious events recorded in the groups, but the broader safety details remain limited.

In general, the absence of recorded serious events in a small study does not establish that an event cannot occur or provide a precise estimate of its frequency. The counts should be read as a description of the events recorded among the participants at risk, not as a comparative safety test. The non-randomized design also means that differences between groups cannot be interpreted as randomized evidence about dose-related safety.

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

The registry record establishes that a completed Phase 1 study examined single oral doses of nerandomilast in healthy Japanese men, with parallel groups receiving 9 mg or 18 mg. It specifies a primary pharmacokinetic endpoint, AUC0-inf, and describes the analysis population and sampling schedule. These details clarify the question the study was designed to address: characterization of plasma exposure after dosing.

The record does not report the primary endpoint results. Without group-specific AUC0-inf estimates, measures of variability, or confidence intervals, there is no basis in the posted information for stating whether exposure differed between the dose groups, how large a difference was observed, or how precisely exposure was estimated. The registry’s endpoint definition is not itself a result.

Even with endpoint estimates, this design would require cautious interpretation. Participants were not randomly allocated, the study was open-label, and there was no described placebo or untreated control group. The registry does not report the process used to assign dose or any adjustment for group differences. A dose-group contrast would therefore not have the same interpretation as a randomized comparison.

The trial is not a clinical efficacy study in patients with a disease. A pharmacokinetic exposure measure describes drug concentrations over time; it does not establish a clinical benefit, a clinical harm, or a treatment effect on a health outcome. Nor can findings in healthy Japanese men automatically be generalized to other populations or settings. The record does not report data that would support those broader conclusions.

The safety counts are also limited: there were no serious adverse events or deaths recorded in either group, and the other-adverse-event counts were one in the 9 mg group and none in the 18 mg group. Those observations describe the registry entries but do not provide a complete safety profile or a reliable comparative assessment. Overall, the record defines the pharmacokinetic question and reports limited safety counts, while leaving the primary numerical results and several analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a well-defined endpoint and a reported result. The registry names AUC0-inf, states its units and summary scale, and gives the sampling schedule. Those elements explain what the investigators sought to measure. Yet without the endpoint estimates and their variability, readers cannot assess the actual exposure values or their precision. A statistical interpretation depends on both a clearly described measure and the results needed to evaluate it.

The design also illustrates why allocation matters when comparing groups. Non-randomized dose groups can differ for reasons beyond dose, and a parallel-group contrast does not automatically isolate a dose effect. The lack of a reported assignment procedure leaves the extent of that concern uncertain. The design should therefore shape the strength and scope of any interpretation, independently of the endpoint definition.

Another statistical distinction is between a planning illustration and an observed study result. The registry describes sample-size calculations based on an observed effect, but such calculations do not establish the original design rationale, demonstrate adequate precision, or represent observed power. No specific planning estimates or trial-specific sample-size justification are reported in the registry record. This distinction is important because a planning exercise cannot fill in missing endpoint results.

The population definition is also relevant. The primary analysis was intended to include treated participants with at least one evaluable pharmacokinetic endpoint, subject to exclusions for relevant protocol deviations or pharmacokinetic non-evaluability. The actual size of that population and the handling of missing measurements are not reported. Without those details, enrollment alone cannot show how much information contributed to the primary analysis.

Finally, the safety counts demonstrate the limits of sparse descriptive data. They record the observed events but provide little detail about event characteristics or comparative uncertainty. Taken together, the study’s statistical value lies in the question and measurement framework it documents; the registry’s missing numerical endpoint results prevent assessment of the principal pharmacokinetic findings.

14. 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 most important limitation of the registry record is that it does not report the primary endpoint values. The group-specific AUC0-inf geometric means and geometric coefficients of variation are absent, as are confidence intervals or a reported comparison. This prevents assessment of the direction, magnitude, and precision of the pharmacokinetic findings.

The design was non-randomized and open-label. The method of assigning participants to dose groups is not reported in the registry record, and no adjusted analysis is described. Any between-group comparison would therefore need to be interpreted cautiously because the record does not establish that the groups were otherwise comparable.

The record reports enrollment of 12 and lists 6 participants at risk for serious adverse events in each group, but does not report the primary pharmacokinetic analysis-set size. It also does not describe participant flow, missing samples, reasons for exclusions, or how missing data were handled. The analysis-population definition alone cannot resolve those uncertainties.

The study involved healthy Japanese men and single doses of 9 mg and 18 mg. The registry does not report clinical outcome data, repeated-dose results, or results in other populations. Its scope is therefore limited to the stated pharmacokinetic objective and the information recorded for these dose groups; broader conclusions are not supported by the registry record.

Safety reporting is limited to event counts. The record does not give the non-serious event term or details about severity, timing, outcome, or relationship to treatment. It also does not report a statistical analysis plan, multiplicity procedures, interim analyses, or the trial’s own sample-size justification. Those details are not reported in the registry record and should not be assumed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Test How Different Doses of Nerandomilast (BI 1015550) Are Taken up in the Body of Healthy Japanese Men — NCT06139302.
• Registry record last updated 2025-12-01; status last verified 2025-10.
• Results first posted 2025-12-01.
• 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.

18. Record Summary

NCT06139302 is a completed, open-label, non-randomized, parallel-group Phase 1 study of single oral nerandomilast doses in healthy Japanese men. The registry records enrollment of 12 and describes groups receiving 9 mg or 18 mg.

The primary endpoint was plasma AUC0-inf, summarized as a geometric mean with geometric coefficient of variation. Sampling was scheduled from before dosing through 144 hours after dosing. The registry describes a pharmacokinetic analysis population but does not report its size or the primary endpoint values.

No serious adverse events or deaths were recorded in either group; other adverse events were recorded for 1 participant in the 9 mg group and none in the 18 mg group. The registry does not report the event details, a full statistical analysis plan, missing-data handling, or the trial’s own sample-size justification.