A Study to Compare How Different Medicines (Rosuvastatin, Digoxin, Metformin, and Furosemide) Are Handled by the Body of Healthy People and People With Liver Cirrhosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Compare How Different Medicines (Rosuvastatin, Digoxin, Metformin, and Furosemide) Are Handled by the Body of Healthy People and People With Liver Cirrhosis (NCT05741372), a non-randomized na study. The primary outcome is Area Under the Concentration Time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24).

2. Clinical Question

The broader purpose was to characterize how the body handles four medicines in people with and without cirrhosis. The registry describes the medicines as probes relevant to transporter profiling, an approach intended to help understand how medicines in development may be handled in people with liver cirrhosis. The primary endpoint focuses specifically on rosuvastatin; the registry also lists other outcome measures, but their numerical results are not reported in the registry record.

This is a pharmacokinetic question about measured drug concentrations and exposure, not a trial designed to compare clinical benefit. The primary endpoint is an exposure measure, and no conclusion about treatment benefit or clinical outcomes follows from it alone. Since participants were assigned to groups according to health status rather than randomized, any observed group differences could reflect differences between the groups as well as cirrhosis status. The registry record does not report numerical endpoint estimates or a statistical test result, so the direction and precision of the primary comparison cannot be assessed from the posted results.

3. Trial Design

This completed study was a parallel-group, non-randomized trial with no masking. Enrollment was 28. The registry lists three groups: healthy participants, participants with F4 cirrhosis meeting Child-Pugh A criteria, and participants with F4 cirrhosis meeting Child-Pugh B criteria. The Child-Pugh A group is described as compensated and the Child-Pugh B group as decompensated. Because participants were not randomized to health-status groups, the design is observational with respect to the comparison between healthy participants and participants with cirrhosis.

All participants received a single dose of rosuvastatin, digoxin, metformin hydrochloride, and furosemide as an oral cocktail. The group descriptions state that dosing occurred on Day 1 after a standardized light breakfast and with 280 ml of water. The dose descriptions in the registry record are truncated, so the full regimen cannot be established from the record. Participants with cirrhosis continued their regular treatment for the condition during the study.

The study was intended to last about 1 month for each participant. Participants visited the study site 4 times, including an overnight stay of 2 nights. Blood samples were collected frequently to assess the main pharmacokinetic endpoint; the registry lists sampling from within 2 hours before dosing through 24 hours after dosing. Health checks and recording of unwanted effects were also described.

The recorded study start was 2023-09-07, primary completion was 2024-12-18, and status is completed. The phase is listed as NA. The registry record does not report a randomized assignment procedure, masking, a sample-size justification, or an explanation of how the enrollment target was chosen. With non-random allocation, group comparisons can describe differences in measured exposure, but they cannot isolate the effect of cirrhosis from all other differences between groups.

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: Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all patients as required.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetics (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. 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): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Concentration Time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24), measured over Within 2 hours (hrs) before and at 30 minutes (min), 1 hrs, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 24 hrs after drug administration..

The primary endpoint is the area under the plasma concentration-time curve for rosuvastatin from 0 to 24 hours, abbreviated AUC0-24. It is expressed in hours*nanomole/liters (h*nmol/l). AUC represents accumulated drug concentration over a specified time interval: it draws on concentration measurements collected at multiple times rather than relying on a single blood sample. The 0-to-24-hour interval captures exposure over the first day after the study dose.

Pharmacokinetic exposure measures are used to characterize how a medicine is handled by the body. In this study, comparing rosuvastatin AUC0-24 across the healthy, Child-Pugh A, and Child-Pugh B groups addresses whether measured exposure differed among those groups under the study conditions. The endpoint is relevant to the study’s transporter-profiling aim, but AUC by itself does not identify the biological mechanism responsible for a difference. Nor is it a direct measure of clinical benefit or harm.

The registry states that the endpoint was log transformed before analysis and that adjusted geometric means and adjusted geometric standard errors were calculated. The registry record does not report the numerical AUC estimates, their standard errors, confidence intervals, or a test of group differences. Therefore the magnitude, direction, and precision of any group contrast cannot be described from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint was analyzed with an analysis of variance (ANOVA) model after natural-log transformation. The model included group, age, and BMI as fixed effects. The registry says adjusted geometric means and adjusted geometric standard errors were calculated. It does not report the fitted estimates or the full model output.

Why analyze a logarithmic endpoint?

General statistical explanation: Pharmacokinetic measurements are often positive and may vary multiplicatively: a change can be understood as a proportional difference rather than a fixed additive amount. A logarithmic transformation can make a skewed distribution more suitable for a model that works with additive effects. When estimates are translated back to the original scale, geometric means describe a typical level on a multiplicative scale. The transformation does not itself remove confounding or make groups comparable; those issues depend on design and model assumptions.

In this record, the analysis is explicitly described as taking the natural logarithm of the endpoint before fitting the ANOVA model. It is not reported whether model assumptions were checked, what diagnostics were used, or whether any alternative analysis was planned. The registry record also does not give the model coefficients, residual summaries, or estimated contrasts.

What does adjustment for age and BMI mean?

General statistical explanation: Covariate adjustment estimates group differences while accounting for the covariates included in the model. Here, age and BMI were included alongside group, and all effects were treated as fixed. This means the reported group estimates would be conditional on that specified model rather than simple unadjusted summaries of each group.

Adjustment is limited to variables and relationships represented in the model. It does not guarantee that group differences are attributable only to cirrhosis, especially in a non-randomized study. The registry record does not report whether other possible sources of group differences were considered, how covariate values were handled, or whether interactions were tested. Those details should not be assumed.

How should standard errors and confidence intervals be read?

General statistical explanation: A standard error describes the estimated sampling variability of an estimate under a statistical model. A smaller standard error generally indicates a more precise estimate, while a larger one indicates more uncertainty. A confidence interval presents a range of values compatible with the data and model at a stated confidence level. It communicates precision as well as the estimate’s direction and magnitude. Neither a standard error nor a confidence interval measures the importance of a result by itself.

The registry specifies adjusted geometric standard errors as the dispersion measure for the primary endpoint, but numerical values are not reported in the registry record. A confidence interval is not described in the available primary endpoint details. Thus, even though the type of summary is identified, the actual precision of the group estimates cannot be assessed.

Why can group balance and allocation matter?

General statistical explanation: Random allocation can help balance measured and unmeasured participant characteristics on average. In a non-randomized comparison, group membership may be related to characteristics that also influence the outcome. A model can adjust for recorded covariates, but adjustment cannot reliably account for unmeasured factors and depends on correct model specification.

Here, allocation is recorded as non-randomized and masking as none. The groups represent healthy participants and participants classified by cirrhosis status, rather than treatment arms assigned by chance. Therefore the group estimates should be interpreted as adjusted comparisons among the enrolled groups, not as effects caused solely by cirrhosis. The record does not describe a strategy for controlling unmeasured confounding.

What can the described model establish?

The stated ANOVA model describes how the investigators intended to estimate adjusted group-level exposure summaries after log transformation. The choice of model does not establish the result: numerical estimates and uncertainty are needed to judge what the data indicate. Those results are not reported in the registry record. The record also does not report the planned pairwise contrasts, any overall group test, the significance threshold for the primary analysis, or whether inferential tests were conducted.

The sample-size assumptions listed for planning illustrations are not the study’s own design justification. They describe an illustration based on an observed effect, equal allocation between two arms, a two-sided significance level of 0.05, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. The record does not report a protocol-based sample-size rationale. Such planning calculations are not observed power, and they cannot substitute for estimates and uncertainty from the actual study.

Overall, the methods description tells readers the endpoint scale, transformation, model family, adjustment variables, and form of the reported summaries. It does not provide enough output to reconstruct or independently assess the primary comparison. No recalculated result is described in the registry record, and the registry does not report a discrepancy between sponsor and recalculated analyses.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 16 analyses, while identifying rosuvastatin AUC0-24 as the primary endpoint. The broader study assessed four medicines and included three participant groups. When a study evaluates multiple endpoints, drugs, time periods, or group contrasts, the chance of at least one apparently notable result can increase if many statistical tests are conducted. Statistical approaches to multiplicity can control or describe that risk, but the appropriate approach depends on which outcomes and comparisons were planned.

The registry record does not report a multiplicity adjustment, a hierarchy of secondary endpoints, or how testing across outcomes and contrasts was handled. It also does not report whether each of the 16 analyses was confirmatory or exploratory. Without that information, a reader cannot determine how to interpret any individual test result in the context of the broader set of analyses. Numerical results for the primary endpoint are not reported in the registry record, so no claim about statistical significance can be assessed in any case.

Missing-data handling is also not described in enough detail to evaluate. The primary endpoint population is identified as a pharmacokinetic parameter analysis set. This set included treated participants who had at least one pharmacokinetic endpoint defined as primary and were not excluded because of a protocol deviation relevant to pharmacokinetic evaluation or pharmacokinetic non-evaluability. The registry record does not report the number of participants included in that set for the primary endpoint, the number excluded, the reasons for missing measurements, or how incomplete concentration profiles were handled.

The distinction between enrollment, treatment, and analysis populations matters because not every enrolled participant necessarily contributes an evaluable endpoint. The registry gives an enrollment of 28, while the listed safety risk sets are reported separately by group. The primary analysis denominator and participant flow are not reported in the registry record. No assumptions about imputation, replacement of missing samples, or sensitivity analyses should be inferred.

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 lists serious adverse event counts of 0 among 11 participants at risk in the healthy group, 0 among 11 in the Child-Pugh A group, and 0 among 6 in the Child-Pugh B group. Deaths are listed as 0 in each group. Other adverse events are listed for 3 of 11 participants in the healthy group, 3 of 11 in the Child-Pugh A group, and 0 of 6 in the Child-Pugh B group. These are descriptive counts, not comparative estimates adjusted for differences between groups.

A zero serious-event count means that no serious adverse event was recorded in the listed risk set during the reporting period. It does not show that the underlying risk is zero. Event counts can be imprecise, particularly in small groups, and the registry record does not provide confidence intervals or a detailed account of follow-up for safety outcomes.

The posted record does not identify the terms for the other adverse events, their severity, timing, relationship to a study medicine, or whether participants experienced more than one event. It also does not give a definition of the safety risk period in the listed results. Therefore, the counts do not support a detailed comparison of event types or attribution. They should be read as the recorded summary of observed events in these study groups, not as a general safety conclusion about the medicines.

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

This study addresses a pharmacokinetic question: how rosuvastatin exposure over 24 hours was assessed in healthy participants and participants with F4 cirrhosis classified as Child-Pugh A or B. The broader study administered rosuvastatin, digoxin, metformin hydrochloride, and furosemide together as a single oral cocktail. The registry record describes frequent blood sampling and an adjusted analysis of the primary rosuvastatin endpoint.

However, the numerical estimates for that endpoint are not reported in the registry record. The direction and size of the observed group differences cannot therefore be stated, and their precision cannot be judged. No primary-endpoint confidence intervals or p-values are reported in the available record. The methods description alone does not establish whether groups differed in exposure.

Even if numerical exposure estimates were available, their interpretation would remain tied to this design and setting. Participants were not randomized to healthy or cirrhosis groups, so measured differences would be comparisons among groups that may differ in other ways. The stated model adjusts for age and BMI, but the record does not establish that all relevant differences were measured or controlled.

The endpoint also has a specific scope. It measures plasma exposure over the first 24 hours after a single dose under the described study conditions. It does not, by itself, answer questions about repeated dosing, longer-term exposure, clinical outcomes, or the effects of changing a treatment regimen. The study’s stated aim to support understanding of how medicines in development are handled in cirrhosis is broader than the primary endpoint alone, but the registry’s missing numerical results limit what can be concluded from the posted record.

The safety summary records no serious adverse events or deaths in the listed groups, with other adverse events recorded in the healthy and Child-Pugh A groups. These observations are limited to the participants and reporting period captured in the record. They do not establish that serious events cannot occur, and they do not resolve whether an event was caused by a study medicine.

The appropriate reading is therefore restrained: the registry describes a completed study and a planned adjusted analysis of rosuvastatin exposure, but does not report the primary numerical findings. It supports understanding of the question and design, not a conclusion about the observed magnitude, clinical significance, or cause of any group difference.

13. Why This Trial Matters Statistically

Pharmacokinetic studies in people with liver disease can help characterize whether drug exposure differs across health-status groups. That question is relevant to medicine development because exposure is one component of how a medicine is handled by the body. This study is structured around a cocktail of four medicines and three groups, with the primary endpoint focused on rosuvastatin AUC0-24.

Statistically, the study illustrates why design and analysis need to be considered together. Its adjusted analysis uses a logarithmic endpoint and includes group, age, and BMI as fixed effects. These details tell readers how the primary summaries were intended to be estimated. At the same time, the non-randomized grouping means that adjustment cannot be interpreted as equivalent to random allocation. The estimates, if reported, would describe modeled differences among the enrolled groups and would need to be considered in light of potential confounding.

The record also shows why complete reporting is essential to interpretation. Naming an endpoint and an analysis method is not enough to establish what the study found. Readers need numerical estimates and measures of uncertainty to understand direction, magnitude, and precision. The absence of those primary results in the registry record prevents that assessment, regardless of the detail in the endpoint definition.

Finally, the study’s multiple medicines, group comparisons, and listed analyses make transparent reporting of multiplicity and analysis populations important. The record does not describe how multiplicity was addressed or provide full participant flow into the pharmacokinetic analysis set. Those gaps limit assessment of how robustly the reported analysis, if available elsewhere, would represent the enrolled participants and the set of questions studied.

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 for interpreting the posted results is that the numerical primary endpoint findings are not reported in the registry record. Without adjusted geometric means, uncertainty estimates, or group contrasts, it is not possible to assess the direction, magnitude, or precision of rosuvastatin exposure differences. The record identifies the analysis but does not supply the results needed to interpret it.

The non-randomized design is another important limitation. Group membership was based on health status and cirrhosis classification, so differences between the groups may reflect more than cirrhosis alone. Although age and BMI were included in the stated model, the registry does not report whether other potentially relevant characteristics were adjusted for. It also does not report model diagnostics or sensitivity analyses.

The arm descriptions are truncated, including the full dosing information. The record states that the medicines were administered as a single oral cocktail after a standardized light breakfast and with 280 ml of water, but the complete regimen cannot be recovered from those descriptions. It is also not reported whether any concomitant medicines or other participant characteristics influenced the measured exposure.

The primary analysis population is described by eligibility criteria, but the number of participants analyzed and the handling of missing or non-evaluable pharmacokinetic data are not reported. The record does not provide enough detail to assess potential exclusions or incomplete concentration profiles. It also does not describe multiplicity handling across the listed outcomes and analyses.

Safety results are brief: serious events and deaths are reported as zero in each group, while other adverse events are recorded in some groups. Event terms, severity, timing, attribution, and the safety reporting period are not reported in the registry record. These limits mean the safety counts should be treated as a narrow descriptive summary.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Compare How Different Medicines (Rosuvastatin, Digoxin, Metformin, and Furosemide) Are Handled by the Body of Healthy People and People With Liver Cirrhosis — NCT05741372.
• Registry record last updated 2026-01-13; status last verified 2025-12.
• Results first posted 2026-01-13.
• 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

NCT05741372 is a completed, non-randomized, parallel-group study sponsored by Boehringer Ingelheim. It enrolled 28 participants and compared healthy participants with participants with F4 cirrhosis classified as Child-Pugh A or Child-Pugh B. Participants received a single oral cocktail of rosuvastatin, digoxin, metformin hydrochloride, and furosemide.

The primary endpoint was rosuvastatin AUC0-24 in plasma. The stated analysis used natural-log transformation and an ANOVA model with group, age, and BMI as fixed effects, producing adjusted geometric means and adjusted geometric standard errors. The numerical primary endpoint findings are not reported in the registry record.

The listed serious adverse event and death counts are zero in each group; other adverse events are recorded in the healthy and Child-Pugh A groups. Interpretation is limited by non-random allocation, missing numerical endpoint results, and incomplete reporting of analysis populations, missing data, multiplicity, and adverse-event detail.