A Study to Test How BI 1015550 is Taken up in the Blood of People With and Without Liver Problems: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Test How BI 1015550 is Taken up in the Blood of People With and Without Liver Problems (NCT05661344), a non-randomized phase 1 study. The primary outcome is Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz).

2. Clinical Question

The question is pharmacokinetic: it concerns the amount of the active enantiomer measured in plasma over time after dosing. The study also assessed safety and tolerability, but the registry record does not report numerical primary pharmacokinetic results. The study therefore defines a comparison and an endpoint, without establishing from the reported information how large any exposure difference was or how precisely it was estimated.

3. Trial Design

This completed Phase 1 study enrolled 28 participants and used an open-label, non-randomised, parallel, individual-matched design. Participants received a single oral dose of BI 1015550. The study began on 2023-02-07 and reached primary completion on 2023-09-13. The registry describes the study as completed.

The groups comprised participants with normal hepatic function, mild hepatic impairment, and moderate hepatic impairment. Mild impairment was classified as Child-Pugh A, with a score of 5 to 6 points; moderate impairment was Child-Pugh B, with a score of 7 to 9 points. Normal-function participants were individually matched to participants in the impairment groups. The registry describes normal-function participants matched to the mild group separately from those matched to the moderate group.

All groups received the same stated dose and administration conditions: one 18 milligram film-coated tablet with 240 milliliter of water after an overnight fast of at least 10 hours. The study summary says participants were in the study for about 2 weeks and attended the study site 6 times. On the second visit, participants stayed overnight for 4 nights. Blood samples were collected to measure BI 1015550 concentrations, and health checks were conducted to record unwanted effects.

Because allocation was non-randomised, the impairment groups were not created by random assignment. Matching defines the intended comparison structure, but does not make the design equivalent to a randomised trial. Details of the matching criteria beyond individual matching, and any procedures used to address remaining group differences, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: All participants were screened for eligibility prior to participation in the trial. Participants attended a specialist site which ensured that the participants strictly met all inclusion and none of the exclusion criteria. Participants were not to be entered in the trial if any of the entry criteria were violated.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic parameter analysis set (PKS) included all participants in the treated set who provided at least 1 primary or secondary PK endpoint and who were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Thus, a participant was to be included in the PKS even if they contributed only 1 of the main PK parameter value to the statistical assessment. Descriptive and model-based analyses of PK parameters were based on the PKS.

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) included all participants who were treated with 1 dose of trial drug.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz), measured over Within the 2 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 hours after drug administration..

The primary endpoint is the area under the plasma concentration-time curve of R-BI 1015550 from 0 to the last quantifiable data point, abbreviated AUC0-tz. The registry identifies R-BI 1015550 as the pharmacologically active enantiomer, measured using a chiral bioanalytical assay. The unit is hour*nanomole/liter (h*nmol/L).

In general, an area under a concentration-time curve represents drug exposure across the measured time course: it incorporates concentrations over time rather than relying on a single blood measurement. It is used in pharmacokinetic studies to compare systemic exposure between groups. AUC0-tz ends at the last quantifiable measurement, so its value depends on the observed concentration profile and the endpoint’s specified measurement interval.

For this study, blood sampling was scheduled within the 2 hours before dosing and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 hours after administration. The registry states that adjusted geometric means and adjusted geometric standard errors were calculated. It does not report the resulting AUC0-tz estimates, comparisons, or confidence intervals, so the endpoint’s magnitude and precision cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Why analyse the endpoint on a logarithmic scale?

The registry states that pharmacokinetic endpoints were transformed using the natural logarithm before the analysis of variance model was fitted. In general, exposure measures are positive and may have a right-skewed distribution. A logarithmic scale can make relative differences easier to model and can reduce the influence of a long upper tail. These are general statistical reasons for log transformation, not additional findings about this study’s data.

After modelling on the logarithmic scale, the adjusted estimates were back-transformed to the original scale. The registry describes the resulting summaries as geometric least-squares means, also called adjusted geometric means, and adjusted geometric standard errors. A geometric mean is a summary suited to multiplicative scales; it should not be read as an arithmetic average. The registry does not give the resulting estimates or standard errors.

What does the analysis of variance model represent?

The specified model included degree of hepatic impairment as a fixed effect and matched pair as a random effect. In general, a fixed effect represents the particular group contrast being evaluated, while a random effect can account for structure arising from matched observations. This is consistent with the study’s individual-matched design. The model was fitted separately for the mild and moderate impairment groups, rather than combining both impairment categories into one analysis.

The registry’s description does not specify all model details. For example, it does not report the exact contrast parameterisation, diagnostic checks, treatment of influential observations, or whether any additional covariates were included. Those details should not be inferred from the stated fixed and random effects alone.

What do standard errors and confidence intervals convey?

The reported dispersion measure is a standard error, described as an adjusted geometric standard error. In general, a standard error expresses the estimated uncertainty of a statistic under a model; it is not the spread of individual participant values. A confidence interval is often used to communicate uncertainty around an estimate or contrast. The registry description does not state that confidence intervals were reported, and none of their values are available in the registry record. A standard error by itself would not supply the full individual-level distribution or settle the interpretation of a comparison.

Why does matching matter to the model?

The study matched participants with normal hepatic function to participants with mild and/or moderate impairment. The model’s matched-pair random effect reflects that the analysis was designed to account for this pairing. In general, matched analyses use the relationship within pairs rather than treating all observations as unrelated. The benefit depends on the matching structure being correctly represented and on the pairs being informative for the comparison. The registry does not describe the matching variables or provide enough information to assess how well matching balanced the groups.

What does non-randomised allocation imply?

Participants were not randomly allocated to hepatic-function categories; these categories describe participants’ liver status. In general, non-randomised comparisons can be affected by differences between groups other than the characteristic defining the comparison. Matching may address selected features, but it cannot guarantee balance on unmeasured or unmatched factors. Thus, the analysis estimates a model-based comparison within this study’s design, rather than a comparison created by random assignment.

The open-label design means the study was not masked. The principal endpoint is a laboratory concentration-based measure, but the registry does not report procedures for blinded laboratory assessment or details of assay quality control beyond identifying the chiral bioanalytical assay. Such procedures should not be assumed.

How should planning illustrations be interpreted?

The registry’s planning assumptions describe an illustration computed from an observed effect, not a design justification for this trial. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set at a stated fraction of the observed effect. For time-to-event illustrations, the stated output is a total event count; for other outcomes, it is participants per arm. These are planning quantities, not observed participant outcomes and not observed power. Because the numerical observed effect and planning outputs are not reported in the registry record, no numerical sample-size interpretation is possible from the available information.

In general, planning estimates depend on the effect size and assumptions used. An illustration based on an observed effect can show how a hypothetical future design might be sized under specified conditions, but it does not establish that the present study was planned with those conditions or that it had a particular probability of detecting an effect.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is identified as AUC0-tz for R-BI 1015550. The registry also lists a secondary outcome: the area under the concentration-time curve from 0 extrapolated to infinity, AUC0-∞. It reports 3 outcome measures and 6 analyses, but does not provide enough detail in the available record to reconstruct all outcome-analysis pairings or determine how the analyses were organised.

Multiplicity concerns arise when several outcomes, groups, time points, or analyses are examined. In general, a larger family of statistical tests can increase the chance of at least one apparently notable result if no adjustment or hierarchy is used. Whether multiplicity adjustments, a testing hierarchy, or another strategy was prespecified is not reported in the registry record. No adjustment method should therefore be assumed.

The primary outcome description defines a pharmacokinetic analysis set as treated participants who contributed at least 1 primary or secondary pharmacokinetic endpoint and were not excluded for a protocol deviation relevant to pharmacokinetic evaluation or for pharmacokinetic non-evaluability. The registry text ends before completing its further explanation of participant eligibility. Additional analysis-population details are not reported in the registry record.

Specific procedures for missing endpoint data, incomplete concentration profiles, values below assay quantification limits, or other non-evaluable measurements are not reported in the registry record. The endpoint’s definition refers to the last quantifiable data point, but that does not by itself describe how missing or non-evaluable data were handled in the analysis. The registry also does not report whether sensitivity analyses were conducted.

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 safety record lists 8 participants at risk in each of four groups: normal hepatic function matched to mild impairment, mild impairment, normal hepatic function matched to moderate impairment, and moderate impairment. No serious adverse events and no deaths are listed in any of these groups. Other adverse events are listed for 2 participants in the normal-function group matched to mild impairment, 2 in the mild impairment group, 1 in the normal-function group matched to moderate impairment, and 2 in the moderate impairment group.

These are group counts, not rates calculated across a shared follow-up period. The record does not provide event descriptions, event severity beyond the serious versus other categories, timing, duration, or the number of events per affected participant. It also does not specify a safety observation window in the information. The two normal-function groups are defined by their separate matching comparisons, and the record does not clarify whether participants overlap across those listings; their counts should not be added to infer unique participants.

Zero serious events recorded in these groups means none are listed in the registry’s group summaries. It does not establish that an event is impossible or rule out uncommon harms. These safety counts describe the study record and are not a basis for treatment advice.

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

This study was designed to compare plasma exposure to R-BI 1015550 after a single oral dose among participants with normal hepatic function and participants with mild or moderate hepatic impairment. The primary endpoint, AUC0-tz, captures exposure across the observed concentration-time interval. The registry specifies a matched comparison and a log-scale analysis, but does not report the numerical primary endpoint results.

As a result, the registry information does not establish the direction or magnitude of a difference in exposure between either impairment group and its matched normal-function group. It also does not show how precise any estimated difference was. Without the reported estimates and uncertainty measures, it is not possible to judge whether the observed data were compatible with a small or a large contrast.

The design also limits what a comparison can mean. Participants were not randomly assigned to hepatic-function groups. Individual matching is part of the design, and the analysis included matched pair as a random effect, but the record does not give matching criteria or show how other participant characteristics were handled. Statistical adjustment cannot be assumed to remove all differences between non-randomised groups.

The study concerned a single dose and a pharmacokinetic endpoint. The registry summary describes monitoring for unwanted effects, and the safety record lists no serious adverse events or deaths in the groups. These observations are limited to the listed participants and the record’s reporting; they do not establish what might occur in other settings or with different exposure patterns. No clinical efficacy outcome is reported in the information available.

Accordingly, the appropriate reading is narrow: the registry records a completed pharmacokinetic comparison, describes its endpoint and statistical model, and reports limited group-level safety counts. It does not report the primary numerical findings needed to characterise the exposure comparison.

13. Why This Trial Matters Statistically

Hepatic impairment can be relevant to how a medicine is processed in the body, and this study addresses that pharmacokinetic question by measuring concentrations of the active enantiomer over time. From a statistical perspective, the design is notable for using individual matching and separate analyses for mild and moderate impairment rather than treating hepatic impairment as a single undifferentiated category.

The modelling description makes several choices visible: pharmacokinetic endpoints were log-transformed, the analysis used an analysis of variance model, degree of impairment was a fixed effect, and matched pair was a random effect. These choices define how the intended comparison was estimated. Reporting such details matters because the estimate’s meaning depends on both the endpoint and the model used to analyse it.

The design also illustrates why statistical interpretation requires more than identifying a model. The comparison was non-randomised, so matching and model structure should be understood in light of possible differences between groups. The registry’s limited description of matching criteria and lack of numerical endpoint results restrict assessment of both comparability and precision.

For readers evaluating pharmacokinetic evidence, a clearly defined exposure measure is useful, but an endpoint definition alone is not a result. Interpretation requires the estimates and their uncertainty, as well as enough detail to understand the analysis population and handling of incomplete data. Those numerical and procedural details are not reported in the registry record, so the record supports description of the analytical framework rather than a substantive conclusion about the size of the exposure comparison.

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 main limitation for statistical interpretation is that the numerical primary results are not reported in the registry record. No AUC0-tz estimates, between-group contrasts, confidence intervals, or p-values are available in the information described. The direction, magnitude, and precision of the primary comparison therefore cannot be evaluated.

The study is non-randomised and open-label. Matching is reported, but the criteria used to form pairs and the degree of balance achieved are not described. The registry also does not report whether other covariates were considered or how potential residual differences between groups were addressed.

The record describes the primary endpoint model and analysis population in part, but does not complete its description of participant eligibility for the pharmacokinetic set. Handling of missing concentration measurements, non-evaluable profiles, values below quantification limits, and sensitivity analyses is not reported. Multiplicity procedures for the multiple outcomes and analyses are also not reported.

The primary endpoint covers time from 0 to the last quantifiable data point, while a secondary outcome extends the area under the curve to infinity. Numerical results for either endpoint are absent. The registry reports a single-dose study, so the available information does not describe repeated dosing or other treatment settings. The safety summary gives group counts but not event terms, timing, observation window, or participant-level detail. Finally, although overall enrollment is 28, the record lists 8 participants in each of four safety groups and does not clarify overlap between the separately matched normal-function groups.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Test How BI 1015550 is Taken up in the Blood of People With and Without Liver Problems — NCT05661344.
• 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.

18. Record Summary

NCT05661344 is a completed Phase 1, open-label, non-randomised, parallel study of single-dose BI 1015550 in participants with normal hepatic function or mild or moderate hepatic impairment. The registry reports enrollment of 28 and describes individual matching between normal-function participants and participants in the impairment groups.

The primary outcome is plasma AUC0-tz for R-BI 1015550. The stated analysis used a log-scale analysis of variance model with degree of hepatic impairment as a fixed effect and matched pair as a random effect, fitted separately for mild and moderate impairment. Numerical primary outcome results are not reported in the registry record.

The safety listings show no serious adverse events or deaths in the four group summaries, with other adverse events recorded in each group. The registry does not report enough detail to determine event types or clarify overlap between the separate normal-function matching groups.