This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Compare How Different Substances (Caffeine, Warfarin, Omeprazole, Metoprolol, and Midazolam) Are Handled by the Body of Healthy People and People With Liver Cirrhosis (NCT05741385), a non-randomized na study. The primary outcome is Area Under the Concentration Time Curve of Caffeine, Omeprazole and Metoprolol in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05741385 |
| Phase | NA |
| Condition | Liver Cirrhosis |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
Healthy participants and participants with stage 4 (F4) liver fibrosis or cirrhosis. The study descriptions distinguish Child-Pugh A, compensated participants from Child-Pugh B, decompensated participants. The registry record does not report the number assigned to each group.
Intervention
Each participant received one dose of caffeine, warfarin sodium, omeprazole, metoprolol, and midazolam as a cocktail. The summary states that participants with cirrhosis continued their regular treatment for the condition.
Comparator
The study compares the pharmacokinetic measurements across healthy participants and participants with cirrhosis. Allocation was non-randomized, and the registry explicitly cautions that the groups are not a like-for-like control comparison.
Primary question
How do plasma exposure measurements for caffeine, omeprazole, and metoprolol over 0 to 24 hours differ across the study groups? The endpoint is area under the concentration-time curve, a summary of drug concentration over time.
The study’s stated purpose is to assess whether the listed medicines are processed differently in people with liver cirrhosis than in people without liver cirrhosis. The primary endpoint covers three of the five substances in the cocktail; the registry record does not give numerical primary endpoint results. It also does not report separate estimates for each comparison between the healthy, Child-Pugh A, and Child-Pugh B groups.
This question is pharmacokinetic: it concerns concentrations in blood over time, rather than a clinical benefit or disease outcome. The registry record describes the study as a way to understand how medicines in development may be handled in people with cirrhosis. It does not report a treatment-effect estimate or a conclusion about clinical outcomes.
3. Trial Design
This was a completed, non-randomized, unmasked, parallel-group study. The registry record lists enrollment as 4 and phase as not applicable. It describes three groups: healthy participants, participants with F4 Child-Turcotte-Pugh class A cirrhosis, and participants with F4 Child-Turcotte-Pugh class B cirrhosis. The record does not report group-specific enrollment counts or explain how participants were assigned to groups. Because allocation was not randomized, differences between groups may reflect differences in their characteristics as well as differences associated with cirrhosis.
All participants received a cocktail containing caffeine, warfarin sodium, omeprazole, metoprolol, and midazolam. The summary describes one dose of each substance administered by mouth. Participants with cirrhosis continued their regular treatment for the condition during the study. The record describes Child-Pugh A participants as compensated and Child-Pugh B participants as decompensated; it gives examples of disease symptoms in its group description.
Participants were in the study for about 1 month and visited the study site 5 times. One visit involved an overnight stay for 2 nights. Blood samples were collected frequently to assess the main endpoint, with scheduled measurements from 2 hours before drug administration through 96 (+/-12) hours after drug administration. The registry lists the primary endpoint’s measurement interval as 0 to 24 hours, while the sampling schedule extends beyond that interval.
The listed study start was 2023-10-10, primary completion was 2024-08-09, and status is completed. The registry record does not report a protocol rationale for the enrollment, a detailed statistical plan, or the reasons for the group allocation method.
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
| Stage | Child-Pugh A |
|---|---|
| STARTED | 4 |
| COMPLETED | 4 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic parameter analysis set (PKS): All subjects in the treated set (TS) who provide at least one 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.
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): All subjects who signed informed consent and were treated with study drug.
| Characteristic | Unit | Child-Pugh A |
|---|---|---|
| Participants analysed | 4 | |
| Age, Continuous | Years | 66.8 (SD 7.1) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 4 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Concentration Time Curve of Caffeine, Omeprazole and Metoprolol in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24), measured over 2 hours before drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48-72 and 96 (+/-12) hours after drug administration..
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | Hour*nanogram/milliliter |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the area under the plasma concentration-time curve for caffeine, omeprazole, and metoprolol over 0 to 24 hours after administration. The area under a concentration-time curve combines concentration measurements across an interval. It is used in pharmacokinetic research as a summary of systemic exposure during that interval: a curve with higher concentrations over time will generally have a larger area. This is a general explanation of the measure, not a statement about the study’s unreported results.
Concentrations were measured at scheduled times, including measurements before administration and at points extending through 96 (+/-12) hours afterward. The primary endpoint uses only the 0 to 24 hour interval; later sampling times do not, by themselves, change the stated endpoint. The record reports the unit as hour*nanogram/milliliter and specifies that the endpoint is summarized using a geometric mean with geometric coefficient of variation.
These summaries suit measurements that may be positive and right-skewed, as pharmacokinetic concentrations often are. In general, a geometric mean is obtained by averaging on a logarithmic scale and converting back to the original scale. The geometric coefficient of variation describes relative variability on that scale. The registry record does not report the geometric means, variation estimates, group comparisons, or confidence intervals. It therefore does not establish the size or precision of any difference in exposure between the groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes the intended comparison and endpoint, but it does not report the primary endpoint results. It lists no analyses, and no numerical estimates for the plasma exposure of caffeine, omeprazole, or metoprolol are reported in the registry record. There are no reported group contrasts, confidence intervals, or hypothesis-test results from which to assess the magnitude or precision of differences. The completed status indicates that the study is recorded as completed; it does not supply the missing outcome estimates.
The listed enrollment is 4. That small overall enrollment makes it especially important to know the group-specific data and uncertainty, but those details are not reported in the registry record. The record does not give the number of participants contributing primary endpoint data, the distribution of observations across groups, or any reasons that data may have been excluded. Without those details, the extent to which the primary endpoint represents the enrolled participants cannot be assessed.
The non-randomized design also limits interpretation. In a randomized comparison, allocation is intended to balance measured and unmeasured participant characteristics on average. Here, the record says allocation was non-randomized and cautions that the arms are not a like-for-like control comparison. Consequently, even if group estimates were available, an observed difference could not automatically be attributed to cirrhosis alone. Participant characteristics, concurrent care, or other differences between groups could also contribute. The registry record does not report an adjusted analysis that would address such differences.
Geometric means and geometric coefficients of variation are appropriate kinds of summaries for concentration data, but their presence in the endpoint description is not itself a result. No numerical values are available to indicate whether exposure estimates were similar or different, or how variable they were. A confidence interval, if reported, would show the range of values compatible with the data under the analysis assumptions; no such interval is reported.
The adverse-event information is also limited. For the Child-Pugh A group, the registry reports 0 serious adverse events among 4 at risk and 2 other adverse events among 4 at risk, with 0 deaths. These figures describe the recorded safety counts for that group; the record does not supply corresponding safety counts for the healthy or Child-Pugh B groups. Counts from a small group are imprecise descriptions and should not be treated as a comparative safety assessment.
Overall, the registry record supports a description of the study design, sampling plan, endpoint definition, and limited safety counts. It does not support conclusions about the direction, size, or precision of pharmacokinetic differences. Neither an absence of reported results nor a zero count for one safety category is evidence that a drug effect or risk is absent.
9. Statistical Methods Explained
The endpoint is described as a geometric mean, with geometric coefficient of variation as its measure of dispersion. These are statistical summaries for positive measurements that can vary multiplicatively. A geometric mean is calculated by transforming observations to the logarithmic scale, averaging there, and transforming the result back. This makes the summary less dominated by unusually high observations than an arithmetic mean can be when data are right-skewed. This is general statistical context; the registry record does not report the underlying observations or calculated endpoint summaries.
Why summarize concentration with an area under the curve?
A concentration-time profile contains measurements at multiple times. The area under the curve compresses those measurements into a summary of exposure over a specified interval. It retains information about both concentration and time, rather than relying on a single measurement. In this study, the specified primary interval is 0 to 24 hours. The record also gives a broader blood-sampling schedule, so the measured profile extends beyond the interval used for the primary endpoint. The endpoint description alone does not show how concentrations changed or whether profiles differed among groups.
What does a geometric coefficient of variation describe?
Variation indicates how dispersed measurements are around a summary. A geometric coefficient of variation expresses relative variability for data analyzed on a logarithmic scale. In general, it is useful when differences between observations are better understood proportionally than as fixed absolute amounts. It is not a confidence interval and does not directly show the precision of a comparison between groups. The registry record reports the type of dispersion measure planned for the endpoint but does not report its values.
What would a group comparison need to communicate?
A clear comparison would identify the groups being contrasted, report an estimate for each group or a contrast between them, and describe uncertainty. A confidence interval is a range calculated by a statistical procedure to reflect sampling uncertainty under its assumptions. It helps readers judge how compatible the data are with different possible effect sizes. A p-value, if used, summarizes how unusual the observed data would be under a specified null model; it does not measure the probability that a hypothesis is true or the clinical importance of a difference. No group estimates, confidence intervals, or p-values are reported in the registry record.
The study has three described groups, but it is not randomized. A statistical comparison cannot remove the design limitation simply by calculating a contrast. Adjustment can account for measured characteristics if they are recorded and appropriately modeled, but it cannot guarantee removal of confounding from unmeasured or poorly measured characteristics. The registry record does not report an adjusted comparison or identify covariates used in an analysis. It also does not report a detailed statistical analysis plan, so the intended handling of multiple comparisons, distributional assumptions, or model choices is not available.
Why can small samples produce uncertain estimates?
In general, estimates from small samples are sensitive to the observations included. A single participant’s measurements can have substantial influence, especially when the outcome is variable or the groups differ in size. The listed enrollment is 4, but the record does not report group-specific enrollment or the number contributing data to the primary endpoint. This prevents assessment of how many observations supported each group estimate and whether any endpoint data were unavailable or excluded.
The registry describes a pharmacokinetic analysis set consisting of treated subjects who provide at least one primary pharmacokinetic endpoint and are not excluded for a relevant protocol deviation or pharmacokinetic non-evaluability. This definition indicates that the analysis population may be narrower than everyone enrolled or treated. The record does not give the number meeting that definition, the exclusions applied, or how missing measurements were handled.
How should planning calculations be understood?
In general, a sample-size calculation is a planning exercise based on assumptions about a target effect, variability, allocation, and statistical testing. A calculation using an observed effect is an illustration of what a future study might require under those assumptions; it is not an observed measure of power for the completed study. The registry states that its planning illustration uses the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also says the effect to detect is a stated fraction of the observed effect. The numerical planning results and any fraction-specific values are not reported in the registry record. These assumptions should not be mistaken for the trial’s own design rationale or statistical plan.
Over-dispersion is a general concern when variability exceeds what a simple statistical model assumes. If a model underestimates variability, uncertainty intervals can be too narrow and tests can be misleading. For pharmacokinetic data, variability may arise from differences between participants, measurement conditions, or concentration profiles. The record does not report a model for repeated concentration measurements, an assessment of over-dispersion, or a method for handling the dependence among observations from the same participant.
The registry’s endpoint and analysis-set descriptions offer useful definitions, but they do not replace the numerical analysis. Without results, uncertainty estimates, and information on data completeness, readers cannot evaluate whether the endpoint estimates are stable, whether group contrasts are precise, or how strongly they depend on analytic choices.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint names three substances: caffeine, omeprazole, and metoprolol. The registry record does not report whether each substance is analyzed as a separate primary comparison, how comparisons across the three cirrhosis and healthy groups are organized, or whether any adjustment for multiple testing is planned. Multiplicity matters when several outcomes or contrasts are tested because the chance of at least one apparently notable result can increase as the number of tests grows. This is a general statistical consideration, not evidence that a particular adjustment was or was not used.
The record lists 5 outcome measures but gives only the primary endpoint description in the available trial details. The remaining outcome definitions and results are not reported in the registry record. It also lists no analyses. As a result, it is not possible to determine which outcomes were analyzed, whether all planned analyses were completed, or whether the reported analysis corresponds to a prespecified plan.
The stated pharmacokinetic analysis set includes treated subjects with at least one primary endpoint who are not excluded for a relevant protocol deviation or pharmacokinetic non-evaluability. The number included in that set, the number excluded, and reasons for exclusion are not reported in the registry record. The record does not describe missing-data methods, imputation, or sensitivity analyses. In general, missingness can affect interpretation if the availability of measurements is related to participant characteristics or outcomes; the extent and handling of missing data cannot be assessed.
Without an analysis plan, multiplicity strategy, analysis-population counts, and missing-data account, the robustness of any potential result cannot be evaluated. No primary endpoint estimates or statistical tests are reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Child-Pugh A | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Child-Pugh A | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Child-Pugh A | 2 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Child-Pugh A |
|---|---|---|
| Atrioventricular block first degree | Cardiac disorders | 1 of 4 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 4 |
For the Child-Pugh A group, the registry reports 4 at risk for the serious adverse event count, 0 affected by a serious adverse event, and 0 deaths. It also reports 4 at risk and 2 affected for other adverse events. No top serious adverse-event terms are listed. These are the safety figures recorded for Child-Pugh A; corresponding figures for the healthy and Child-Pugh B groups are not reported in the registry record.
These counts should be read as descriptive observations, not as a comparative safety analysis. The registry record does not report event definitions, timing, severity details beyond the serious-event category, or an assessment of whether events were related to study substances. It also does not provide comparative statistical estimates. A zero count means no event in that category was recorded in the reported group; it does not establish that the risk is absent. With the listed enrollment of 4 and no group-specific safety results for the other arms, these figures cannot characterize comparative safety across the study groups.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed study was designed to compare pharmacokinetic measurements across healthy participants and participants with F4 cirrhosis. It identifies the primary measure as plasma area under the concentration-time curve for caffeine, omeprazole, and metoprolol over 0 to 24 hours, with geometric means and geometric coefficients of variation specified as the summaries. It also describes the cocktail, the study groups, and the blood-sampling schedule.
What the record does not establish is whether exposure differed between groups, the size or direction of any difference, or the precision of an estimate. Numerical primary endpoint results and statistical analyses are not reported in the registry record. The listed enrollment of 4 does not by itself reveal how many participants were in each group or contributed evaluable endpoint data. The record therefore cannot support a conclusion that the medicines were handled similarly or differently in the groups.
Even if numerical contrasts were available, the non-randomized design would require caution. Differences between groups could reflect participant characteristics or other factors as well as liver disease status. The registry cautions that the groups are not a like-for-like control comparison, and it does not report an adjusted analysis that might address measured differences.
The safety counts are likewise limited to the Child-Pugh A group. They do not provide a basis for comparing event rates across all groups or for determining causality. A lack of reported results is not a finding of no effect, and a zero serious-event count in the reported group is not proof of no risk. The appropriate interpretation is that the registry documents the study’s design and selected safety counts while leaving the main pharmacokinetic result unresolved.
13. Why This Trial Matters Statistically
This study illustrates how pharmacokinetic research uses concentration measurements over time to ask whether drug exposure varies across clinical groups. An area-under-the-curve endpoint summarizes an entire interval rather than one blood draw, while geometric summaries can describe positively distributed measurements whose differences are naturally proportional. These features make the endpoint relevant to the study’s stated question about how the body handles the cocktail substances.
It also illustrates why design and reporting matter alongside endpoint choice. Non-randomized groups may differ in ways that influence pharmacokinetic measurements, so a contrast is not automatically attributable to cirrhosis. Group-specific counts, adjustment methods, endpoint estimates, and uncertainty would help readers understand what the comparison can support. The registry record does not report these analyses, and its caution that the groups are not like-for-like is important to interpretation.
The enrollment recorded as 4 makes transparent reporting of group membership and data completeness particularly important. Without group sizes and the number of evaluable endpoint records, readers cannot judge how much information supports each estimate. Similarly, without confidence intervals or other uncertainty summaries, the precision of a result cannot be assessed.
The record also demonstrates the distinction between a completed study and a reported result. Completion status and a defined endpoint describe study conduct and intent, but they do not answer the scientific question without numerical findings. For clinical researchers and biostatisticians, clear analysis populations, complete outcome reporting, and explicit handling of missing data and multiple comparisons are essential to determining what evidence a small, non-randomized pharmacokinetic study contributes.
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 largest interpretive limitation is that the registry record reports no numerical primary endpoint results and no analyses. There are no group-specific estimates, comparisons, or uncertainty measures. The completed status does not resolve this lack of results, so the central question about exposure differences remains unanswered in the record.
The total enrollment is recorded as 4, but the registry does not report how participants were distributed across the healthy, Child-Pugh A, and Child-Pugh B groups. It also does not state how many contributed evaluable data to the primary endpoint or describe exclusions. This leaves uncertainty about the amount of information behind any potential estimate.
Allocation was non-randomized, and the registry warns that the arms are not like-for-like controls. This limits causal interpretation because differences in participant characteristics or care could contribute to observed contrasts. The record does not report an adjusted analysis or the covariates that might have been considered.
The primary endpoint covers caffeine, omeprazole, and metoprolol, while the cocktail also includes warfarin sodium and midazolam. The registry record does not provide primary endpoint results for the named substances or explain the other outcome measures in sufficient detail. It does not report the multiplicity strategy, detailed statistical methods, missing-data handling, or a sample-size rationale for the trial’s own design.
Safety reporting is limited in the available record to Child-Pugh A counts. Comparative counts for the other groups, event details, and assessments of relationship to the study substances are not reported. These gaps prevent a broader assessment of safety or of the consistency of findings across groups.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Compare How Different Substances (Caffeine, Warfarin, Omeprazole, Metoprolol, and Midazolam) Are Handled by the Body of Healthy People and People With Liver Cirrhosis — NCT05741385.
- Registry record last updated 2025-09-10; status last verified 2025-08.
- Results first posted 2025-09-10.
- 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.
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18. Record Summary
The registry record describes a completed, non-randomized, unmasked, parallel-group pharmacokinetic study with enrollment of 4. Healthy participants and participants with F4 Child-Pugh A or Child-Pugh B cirrhosis received a cocktail of caffeine, warfarin sodium, omeprazole, metoprolol, and midazolam.
The primary endpoint was plasma area under the concentration-time curve for caffeine, omeprazole, and metoprolol over 0 to 24 hours, summarized using geometric means and geometric coefficients of variation. Numerical primary results and statistical analyses are not reported in the registry record. The reported safety information includes Child-Pugh A counts of 0 serious adverse events, 2 other adverse events, and 0 deaths.