A Study in Healthy People to Test How BI 1015550 is Taken up in the Body When Given With or Without Food: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in Healthy People to Test How BI 1015550 is Taken up in the Body When Given With or Without Food (NCT06415045), a randomized phase 1 study. The primary outcome is Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point) (AUC0-tz).

2. Clinical Question

The study addresses a pharmacokinetic question rather than a clinical-outcome question. It compares drug exposure under two administration conditions within a randomized, two-period, two-sequence crossover design. In a crossover, participants receive both conditions in different periods, so each participant can contribute information under both fed and fasted administration. The registry describes a washout of at least 10 days between periods.

The registry record identifies healthy participants as the study population and does not describe a disease-specific population. It reports the main objective as investigating the effect of food on the pharmacokinetics of BI 1015550 Formulation C2. It does not report a clinical benefit question or a comparison between different drugs. The findings therefore concern measured drug concentrations and exposure under the stated study conditions, not how participants feel or function, or whether a treatment changes a health outcome.

3. Trial Design

This was a completed phase 1, randomized, open-label, single-dose, two-period, two-sequence crossover study in healthy participants. The registry reports enrollment of 18. The comparison was between nerandomilast Formulation C2 after a fast and after a meal. The intervention was a single oral 18 mg film-coated tablet. For the fasted condition, the arm description specifies an overnight fast of at least 10 hours; for the fed condition, it specifies a high fat/high calorie meal. The periods were separated by a washout of at least 10 days.

Randomization assigned participants to one of the treatment sequences. In a crossover design, the sequence determines the order in which each participant receives the conditions. The registry names one sequence as fasted followed by fed, and the other as fed followed by fasted. This approach allows the treatment conditions to be compared while accounting for the fact that measurements from the same participant are related. It also makes period and sequence relevant parts of the analysis.

The study was open-label, with no masking reported. The registry lists a study start of 2024-05-28, a primary completion date of 2024-07-24, and a status of completed. Its official title describes a single-dose, two-period, two-sequence crossover design; the record does not report further operational details beyond the stated meal and fasting conditions and washout.

The primary endpoint was plasma AUC0-tz, the area under the concentration-time curve from time zero to the last quantifiable data point. Blood sampling was scheduled within 3 hours before administration and at multiple specified times after administration, through 144:00 hours. The registry describes three outcome measures and three analyses, but does not report full analysis details for every measure. The result interpreted below is the posted primary comparison of fed and fasted exposure.

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.

period 1

Washout period

Period 2

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.

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 includes all participants who were treated with at least one dose of trial drug.

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 to the Last Quantifiable Data Point) (AUC0-tz), measured over Within 3 hours before Nerandomilast administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 3:30, 4:00, 6:00, 8:00, 11:00, 12:00, 24:00, 34:00, 48:00, 58:00, 72:00, 96:00, 120:00, and 144:00 hours after administration..

The primary endpoint, AUC0-tz, measures the area under the plasma concentration-time curve from the time of administration to the last quantifiable concentration. It summarizes drug exposure over the observed concentration-sampling period. Unlike a single concentration at one time, an area-under-the-curve measure incorporates concentration measurements across time, so it reflects both the magnitude and persistence of measured exposure during that interval.

The endpoint is expressed in hour*nanomol/Liter (h*nmol/L). The registry reports adjusted geometric means for the fasted and fed conditions and a ratio of adjusted geometric means for the comparison. The posted means are 2225.0 for the fasted condition and 2564.0 for the fed condition. The reported fed-to-fasted ratio is 115.21%, with a 90% confidence interval from 106.55% to 124.58%.

Geometric means are used for endpoints analyzed on a logarithmic scale. This is a common approach for pharmacokinetic measures, which can have an asymmetric distribution on their original scale. The ratio directly describes relative exposure between conditions. The endpoint is useful for assessing food-related differences in measured drug exposure, but it does not itself measure symptoms, function, clinical benefit, or harms. The registry also lists AUC0-∞ as a secondary outcome, but the interpretation is focused on the primary AUC0-tz measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint description states that AUC0-tz was analyzed after natural-log transformation using an analysis of variance model. The adjusted geometric means and the ratio were then back-transformed to the original scale. The reported comparison is a ratio of adjusted geometric means, accompanied by a 90% confidence interval. This sequence of steps preserves the statistical analysis on a scale commonly used for pharmacokinetic endpoints while returning the result to a form that can be interpreted as relative exposure.

Why analyze the logarithm of exposure?

In general, pharmacokinetic endpoints are often positive and may vary proportionally rather than by a constant additive amount. A logarithmic transformation can make a strongly right-skewed distribution more suitable for a linear model and can express treatment contrasts as ratios after back-transformation. On the log scale, a difference between conditions corresponds to a ratio on the original scale. This does not make the result a ratio of every participant’s values; it is a comparison of model-adjusted geometric means.

A geometric mean is formed through logarithms and represents a central estimate on a multiplicative scale. It is not the same as the arithmetic mean. The registry identifies the primary endpoint estimate as a geometric least-squares mean, also described as an adjusted geometric mean. Adjustment means the estimate comes from the specified model rather than from a simple unadjusted average. The record gives the method and the resulting point estimates but does not report the standard errors numerically.

What does the crossover model account for?

In general, a crossover analysis must recognize that each participant can receive more than one condition and that measurements from the same participant are related. The stated analysis of variance model includes sequence, subjects within sequences, period, and treatment. Sequence represents the order in which the conditions were given. Period represents when a treatment was received. Treatment represents the fed or fasted condition. Subjects within sequences accounts for participant-level variation within the randomized treatment orders.

Accounting for participant-level variation can make a within-person comparison more informative than treating every measurement as independent. Period and sequence are also relevant because conditions occur in a particular order and at different times. The registry reports these model terms but does not give further details about model diagnostics, assumptions checks, or how potential carryover was assessed. The design includes a washout of at least 10 days, but the record does not state a separate carryover analysis.

How should the confidence interval be read?

A confidence interval describes the uncertainty of an estimate under the statistical model and its assumptions. The 90% interval reported for the fed-to-fasted adjusted geometric mean ratio runs from 106.55% to 124.58%. It indicates a range of ratio values compatible with the observed data under the stated analysis, rather than a range for individual participants or a guarantee about future results. The interval’s width conveys precision: a narrower interval generally indicates greater precision, while a wider one indicates greater uncertainty. Whether that precision is adequate depends on a prespecified decision context, which is not reported in the registry record.

The reference point for equal adjusted geometric means is 100%. In general, an interval containing that reference would be compatible with equal means under the analysis; an interval entirely on one side would indicate that the model-based interval excludes equality. In this result, both reported limits are above 100%. This statistical reading should not be confused with clinical importance. A pharmacokinetic ratio can be estimated precisely without establishing that the magnitude matters to patient outcomes.

What role do sample-size illustrations have?

In general, a sample-size calculation estimates how many participants a future design might need under specified assumptions. It does not describe the observed study’s power after the results are known. The planning illustrations associated with the posted results use a two-sided significance level of 0.05, equal allocation, and a normal approximation; their target effect is expressed as a fraction of the observed effect. They are planning scenarios rather than a record of the original design rationale. The registry does not report the study’s own sample-size justification, and no planning estimate should be interpreted as observed power.

The registry identifies a primary endpoint and also lists AUC0-∞ as a secondary outcome. It reports three outcome measures and three analyses, but does not provide a complete account of the analysis plan for each outcome in the record. No multiplicity procedure, interim-analysis plan, or missing-data method is reported. Those omissions limit what can be inferred about how the primary endpoint was prioritized relative to other analyses, but they do not change the meaning of the posted ratio and confidence interval as the reported primary comparison.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a ratio of adjusted geometric means of 115.21%, with a 90% confidence interval from 106.55% to 124.58%. It also reports the condition-specific adjusted geometric means as 2225.0 h*nmol/L in the fasted condition and 2564.0 h*nmol/L in the fed condition. The endpoint description identifies a log-scale analysis of variance model and lists sequence, subjects within sequences, period, and treatment as model effects.

The registry record does not report a separate recalculated estimate for this primary comparison. The listed recalculation note concerns an endpoint for which values were missing or not estimable for a two-arm comparison; it does not supply an alternative primary ratio. The record’s discrepancy indicator is false, so no disagreement between a sponsor estimate and a recalculated estimate is flagged. There is therefore no separate numerical re-analysis to set against the sponsor’s reported primary result.

For this endpoint, the sponsor’s posted analysis is the available comparison to interpret. Its confidence interval should be read with the model and crossover design in mind. The registry does not report a p-value for the comparison or additional details such as diagnostics and model assumptions checks. These are limitations on interpretation of the available analysis, not evidence that a different result was obtained.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint measuring AUC0-tz and identifies AUC0-∞ as a secondary outcome. It reports three outcome measures and three analyses overall, but only one secondary outcome is identified in the record. The full list of analyses, their hierarchy, and the role assigned to each are not described in detail. A prespecified hierarchy can help distinguish confirmatory questions from exploratory analyses; that hierarchy is not reported in the registry record.

No adjustment for multiple comparisons is reported. In general, when several endpoints or comparisons are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. That general concern does not establish that any specific result is false or that an adjustment was required for this study. The record does not report enough detail to determine whether multiplicity was handled in a protocol or analysis plan outside the registry entry.

The registry does not report an interim-analysis plan. It also does not report a missing-data method, the number of participants included in the primary endpoint analysis, or a detailed account of endpoint exclusions. The defined pharmacokinetic analysis set includes treated participants with at least one eligible primary or secondary pharmacokinetic endpoint, excluding participants for relevant protocol deviations or pharmacokinetic non-evaluability. This definition describes the intended analysis population, but the record does not state how many participants met it for this endpoint or how any missing concentration measurements were handled.

The posted arm entries each list 18 participants. In a crossover study those arm labels describe treatment conditions, not necessarily separate groups of unique participants; the design assigns treatment sequences and participants receive conditions across periods. The registry record does not provide a participant flow account sufficient to reconstruct exclusions or endpoint-specific analysis counts. These gaps mean that readers cannot assess from this record alone whether missing measurements or exclusions could have influenced the estimate.

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 among 18 participants in the fasted condition and zero among 18 participants in the fed condition. It also reports zero deaths in each condition. These figures describe the serious adverse event and death counts recorded for the study; they do not show that the possibility of serious events is absent. In a small study, observing no event is compatible with uncertainty about the frequency of uncommon events.

Other adverse events were reported for 8 participants in the fasted condition and 7 in the fed condition. The registry record does not give the event terms, severity, timing, relationship to treatment, or the overlap of participants who may have experienced events in both periods. Because this was a crossover study, the two condition entries should not be treated as separate groups of unique participants without participant-level information. The counts also do not establish that the fed and fasted conditions differ in safety.

These safety figures are descriptive. The study’s primary question concerned pharmacokinetic exposure, and the record does not provide a comparative statistical analysis of adverse events. The listed counts therefore should not be interpreted as a test of safety equivalence or as evidence that one condition is safer. No medical conclusion follows from the absence of reported serious events in this study alone.

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

The primary result describes relative plasma exposure after a single dose of nerandomilast Formulation C2 under fed and fasted conditions in healthy participants. The reported adjusted geometric mean ratio is 115.21%, and its 90% confidence interval ranges from 106.55% to 124.58%. The interval is entirely above the reference value for equal adjusted geometric means, which means the posted model-based estimate is higher for the fed condition in this study.

This is a pharmacokinetic result, not a clinical outcome result. AUC0-tz captures measured drug exposure from administration to the last quantifiable sample. It does not indicate whether participants experienced an improvement in symptoms, whether a disease outcome changed, or whether the observed exposure difference has a clinical consequence. The registry record does not report a threshold for clinical importance or link the ratio to patient outcomes.

The result is specific to the studied conditions: healthy participants, a single oral dose of the stated formulation, a fasted condition following an overnight fast of at least 10 hours, and a fed condition following a high fat/high calorie meal. It should not be extended automatically to repeated dosing, other meal compositions, other formulations, or people with a particular illness. The record also does not establish the effect of food on outcomes beyond the listed pharmacokinetic measures.

The confidence interval conveys uncertainty in the estimated ratio, but it does not capture every source of uncertainty, such as limits in generalizing from this study population or differences in how meals and dosing might occur outside the study. The registry does not report a sample-size justification, analysis diagnostics, or all details needed to assess those uncertainties. The result is best understood as an estimate of relative exposure under a defined study design, rather than a broad statement about treatment effects.

14. Why This Trial Matters Statistically

This trial illustrates how a crossover design can address a focused pharmacokinetic question. Participants receive both fed and fasted conditions in different periods, and the model accounts for treatment, period, sequence, and participants within sequences. For an endpoint such as plasma exposure, that structure supports a comparison that recognizes repeated observations from the same participants rather than treating the conditions as unrelated groups.

The report also illustrates the importance of interpreting a ratio alongside its confidence interval. A point estimate gives one summary of the relative adjusted geometric means; the interval communicates uncertainty under the analysis. The reported ratio and interval are more informative together than the point estimate alone. At the same time, statistical separation from equal geometric means does not establish clinical importance. The endpoint measures exposure, and no clinical outcome or threshold for meaningful change is reported.

The study also shows why the registry analysis population and design details matter. The record defines a pharmacokinetic analysis set and describes a washout, but does not provide endpoint-specific analysis counts, a detailed missing-data approach, or a sample-size justification. These omissions make it harder to evaluate the full path from enrollment to the reported estimate, even though the primary comparison itself is stated.

Planning illustrations based on an observed effect can help readers consider future study sizes under explicit assumptions. They are not evidence of the original design rationale or observed power. Keeping those distinctions clear helps prevent a small phase 1 exposure comparison from being treated as a definitive result about clinical outcomes, other populations, or different dosing circumstances.

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.

This is a small phase 1 study in healthy participants, with 18 participants enrolled. The registry does not report a sample-size justification or a precision target, so the adequacy of the sample for the primary pharmacokinetic question cannot be assessed against a stated design goal. The reported confidence interval gives information about uncertainty under the fitted model, but it cannot resolve limits in generalizability.

The comparison was open-label and no masking was used. The primary endpoint is a measured pharmacokinetic outcome, which is less dependent on subjective assessment than some clinical outcomes, but the registry does not describe procedures for laboratory blinding or other safeguards. It also does not report model diagnostics, assumption checks, or a separate carryover analysis. A washout of at least 10 days is described, but the record does not provide further evidence about how any period-related concerns were evaluated.

The fed condition was specified as following a high fat/high calorie meal, while the fasted condition followed an overnight fast of at least 10 hours. The result therefore pertains to these stated conditions; the registry does not establish whether other meal types or fasting durations would produce the same exposure estimate. The record also does not describe repeated dosing, and the primary question concerns a single oral dose.

Analysis transparency is limited in several respects. The registry does not report the endpoint-specific number analyzed, missing-data procedures, a full multiplicity strategy, or a detailed participant flow accounting for exclusions. It lists three measures and three analyses but does not provide complete details for each. The posted result also cannot establish a clinical consequence because no patient-centered outcome or clinically meaningful exposure threshold is reported. These limitations should accompany interpretation of the relative exposure estimate.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study in Healthy People to Test How BI 1015550 is Taken up in the Body When Given With or Without Food — NCT06415045.
• 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.

19. Record Summary

NCT06415045 is a completed phase 1, randomized, open-label crossover study in healthy participants, with 18 enrolled. It examined the pharmacokinetics of a single oral 18 mg dose of nerandomilast Formulation C2 in fasted and fed conditions, with a washout of at least 10 days between periods.

The primary endpoint was plasma AUC0-tz. The registry reports adjusted geometric means of 2225.0 h*nmol/L for the fasted condition and 2564.0 h*nmol/L for the fed condition. The fed-to-fasted ratio was 115.21%, with a 90% confidence interval from 106.55% to 124.58%. The analysis used a log-scale analysis of variance model accounting for sequence, subjects within sequences, period, and treatment.

The result concerns relative exposure under the study conditions, not clinical benefit. No serious adverse events or deaths were reported in either condition; other adverse events were reported for 8 participants in the fasted condition and 7 in the fed condition. The registry does not report a sample-size justification, missing-data method, or full multiplicity plan.