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 Renal Impairment Study of Empagliflozin (BI10773) in Japanese Patients With Type 2 Diabetes (NCT01581658), a non-randomized phase 1 study. The primary outcome is Change From Baseline in Total Urinary Glucose Excretion (UGE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01581658 |
| Phase | Phase 1 |
| Condition | Diabetes Mellitus, Type 2 |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 32 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
Japanese patients with type 2 diabetes mellitus, grouped by renal function. The registry lists normal renal function, mild renal impairment, moderate renal impairment and severe renal impairment. The primary outcome population is narrower: treated patients with complete urine samples at baseline and 24 hours. How many treated patients met that analysis-population definition is not reported in the registry record.
Intervention
Oral BI10773, identified as empagliflozin in the trial title, given as a single 25 mg dose. The registry describes the study as assessing pharmacokinetics, pharmacodynamics and safety after that dose. Arm descriptions use the phrase “medium dose” for each of the four groups, so the record does not clarify whether those labels represent any difference in treatment.
Comparator
The renal-function groups provide the comparison: patients with impairment are considered in relation to patients with normal renal function. This is not a randomized treatment comparison. The groups differ by renal-function category, and the registry does not describe a separate placebo or untreated group.
Primary question
How does renal-function category relate to the change from baseline in total urinary glucose excretion over 24 hours after BI10773? The primary endpoint is a pharmacodynamic measure. The study also set out to assess pharmacokinetics and safety, but numerical results for those objectives are not reported in the registry record.
The question is about variation across renal-function groups after a single dose, not about whether BI10773 is better than another treatment. Because allocation was non-randomized and the study was open-label, the group comparison should be read as an observational comparison within a clinical study. The registry record does not report enough numerical endpoint results to establish the size or precision of a difference between groups.
3. Trial Design
This was a Phase I, open-label, parallel-group study with non-randomized allocation. It enrolled 32 participants and is recorded as completed. The listed study dates are 2012-04-01 for the start and 2012-11-01 for primary completion. The condition was type 2 diabetes mellitus, and the study population was Japanese patients with different degrees of renal impairment and patients with normal renal function.
The planned exposure was a single 25 mg dose of BI10773. The record lists four BI10773 groups, described as normal renal function, mild renal impairment, moderate renal impairment and severe renal impairment. The arm descriptions call each a medium-dose tablet single-dose group. They do not explain what distinguishes the repeated “group” labels beyond the renal-function categories. The official study title specifies a single 25 mg dose, while the arm labels use “medium dose”; the registry does not clarify that wording.
In a parallel-group design, participants belong to a group rather than being described as crossing through multiple treatment conditions. Here, the groups correspond to renal-function categories. Since allocation was not randomized, the comparison is not a like-for-like randomized control comparison. Differences between categories could reflect renal function or other differences between the people in those groups; the record does not provide enough detail to assess such differences.
The stated objectives included pharmacokinetics, pharmacodynamics and safety. The primary outcome was change from baseline in total urinary glucose excretion through 24 hours. The registered analysis population for that endpoint consisted of treated patients with complete urine samples at baseline and 24 hours. The record lists three outcome measures and six analyses, but the details of the other measures and analyses 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.
Overall Study
| Stage | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|---|
| STARTED | 8 | 8 | 8 | 8 |
| COMPLETED | 8 | 8 | 8 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Treated patients who had complete urine sample (baseline and 24 hours) for analyses.
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.
| Characteristic | Unit | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 8 | 8 | 8 | 8 | 32 | |
| Age, Continuous | years | 66.8 (SD 3.1) | 67.5 (SD 4.4) | 65.9 (SD 5.5) | 62.0 (SD 7.9) | 65.5 (SD 5.6) |
| Sex: Female, Male: Female | Participants | 4 | 3 | 0 | 2 | 9 |
| Sex: Female, Male: Male | Participants | 4 | 5 | 8 | 6 | 23 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Total Urinary Glucose Excretion (UGE), measured over baseline and 24 hours.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | mg |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline in total urinary glucose excretion (UGE), measured in mg, through 24 hours. The registry describes the measure as the change in total UGE from baseline to 24 hours and gives baseline and 24 hours as the timeframe. The analysis population is treated patients who had complete urine samples at both time points.
In general, urinary glucose excretion quantifies the amount of glucose measured in urine over a defined collection period. A change from baseline describes how the measurement after treatment differs from the starting measurement for the same participant. It is a pharmacodynamic measure: it records a biological response associated with exposure, rather than measuring a patient-centered outcome such as symptoms or daily functioning.
The registry specifies a least-squares mean and a 95% confidence interval as the endpoint summary. In general, a least-squares mean is a model-based mean; its precise adjustment depends on the statistical model. The model and adjustment details are not reported in the registry record. A confidence interval expresses uncertainty around an estimated quantity under the assumptions of its analysis. The numerical estimates and confidence limits for this endpoint are not reported in the registry record, so the observed magnitude and precision cannot be described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a clear primary pharmacodynamic outcome: change from baseline in total UGE through 24 hours after one dose of BI10773. It also specifies the analysis population and the planned summary as a least-squares mean with a 95% confidence interval. However, the numerical primary-outcome estimate and its confidence interval are not reported in the registry record. The direction, magnitude and precision of the observed change therefore cannot be assessed from this record.
The distinction between an outcome definition and an outcome result matters. Naming an endpoint tells readers what was intended to be measured; it does not establish what was observed. Similarly, identifying four renal-function groups does not show whether their results were alike or different. The record does not report numerical group-specific UGE estimates, contrasts between groups, or a statistical test for the primary outcome. It is therefore not possible to characterize a renal-function gradient or the uncertainty around any between-group difference.
The design also shapes interpretation. This was an open-label study with non-randomized allocation. In general, randomization helps make treatment groups comparable with respect to both measured and unmeasured characteristics. These groups were defined by renal-function category rather than assigned at random, so a contrast between them cannot be interpreted as if renal status were randomly allocated. Differences in patient characteristics may accompany differences in renal function. The registry record does not report enough information to evaluate how those characteristics were handled analytically.
The study was intended to examine pharmacokinetics, pharmacodynamics and safety, but the record does not provide numerical pharmacokinetic findings or results for the other outcome measures. For safety, it reports zero serious adverse events in each renal-function group and two other adverse events in the moderate renal impairment group, with zero other adverse events in the remaining groups. The adverse-event terms are not given, and deaths are not reported. These counts are descriptive and do not establish comparative safety.
Accordingly, the posted record supports a description of the study question, design and selected safety counts, but not a numerical conclusion about the primary endpoint. No treatment-benefit claim or conclusion about differences among renal-function categories can be drawn from the endpoint results reported in the registry record.
9. Statistical Methods Explained
The registry describes the primary outcome as a continuous measure summarized by a least-squares mean with a 95% confidence interval. Its actual numerical estimate, confidence limits, model specification and group comparisons are not reported in the registry record. The points below explain the statistical terms generally; they do not fill in the missing analysis details.
What does a least-squares mean represent?
In general, a least-squares mean is an estimated mean produced by a statistical model. Depending on the model, it can represent a group mean adjusted for other included variables or factors. It is not necessarily identical to the simple arithmetic average of the observations. Interpretation depends on which variables, contrasts and assumptions were used. Those details are not reported in the registry record, so the degree of adjustment and the exact meaning of the registered estimate cannot be established.
The endpoint is a change from baseline, so an estimate would describe the modeled average change in UGE among participants included in the analysis. A group-specific change and a difference in change between groups are distinct quantities. To interpret a renal-function comparison, readers would need the group estimates or the explicit contrast, along with its uncertainty. Those numerical results are not reported in the registry record.
How should a confidence interval be read?
In general, a confidence interval is an interval estimate intended to reflect statistical uncertainty under a specified analysis and its assumptions. A 95% confidence interval is not a statement that there is a 95% probability that a particular fixed parameter lies inside the interval. Rather, the confidence level describes the long-run behavior of the interval procedure when its assumptions hold. The width of an interval conveys precision: narrower intervals indicate more precise estimates, while wider intervals indicate greater uncertainty. Since the endpoint estimate and interval limits are not reported, neither precision nor compatibility with different possible effects can be evaluated.
A confidence interval for a group mean is also not automatically an interval for a between-group difference. To assess whether renal-function categories differ, the relevant estimate is a contrast between groups, with its own uncertainty. The registry does not report such a contrast for the primary endpoint. The stated confidence-interval format alone does not supply that comparison.
What does the design imply for comparisons?
In general, non-randomized groups may differ in characteristics other than the factor used to define them. In this study, renal-function categories form the groups; allocation was not randomized. An observed difference between categories could therefore reflect renal-function status, other group differences, or both. Statistical adjustment can address measured variables included in an appropriate model, but it cannot guarantee control of unmeasured differences. The registry record does not report whether adjustment was used or which variables were considered.
Open-label means masking was absent. For an objective laboratory measurement, the consequences of lack of masking depend on how samples are collected, processed and analyzed. Complete urine collection is part of the registered analysis-population definition, but the record does not describe collection procedures or quality-control rules. It is not possible to determine whether measurement or collection practices could have affected results.
What can be inferred from the sample-size illustration?
The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It describes planning for an effect expressed as a stated fraction of the observed effect. Such calculations are design illustrations, not observed power and not a record of the study's original enrollment rationale. Sample-size justification for the trial is not reported in the registry record. The numerical effect used, the resulting planning sizes and the fractions displayed are not reported in the registry record, so they cannot be interpreted.
In general, a planning calculation asks how much information a future study might need under specified assumptions. Its result depends on the assumed effect, variability, analysis and design. A calculation derived from an observed effect can be especially dependent on the stability of that estimate. It does not establish that the completed study had a particular probability of detecting an effect, nor does it replace a confidence interval around an observed estimate.
Why are analysis details important?
For a continuous outcome, the distribution of observations, treatment of missing measurements and model assumptions can influence an estimated mean and its uncertainty. A complete urine sample at baseline and 24 hours is required for the registered primary analysis population. The number excluded for incomplete samples, the handling of other missing information, and any sensitivity analyses are not reported in the registry record. Without these details, readers cannot assess how the analyzed population relates to all treated participants.
The registry lists six analyses, but it does not report their statistical specifications in the record. It does not identify the model terms, whether assumptions were checked, how outliers were handled, or how analyses corresponded to the different outcomes. These omissions limit independent appraisal and reproduction of the statistical analysis. They do not imply that no methods were used; they mean that the methods are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The record lists three outcome measures and six analyses, but it does not provide their full definitions or explain how the analyses relate to one another. The primary outcome is change from baseline in total UGE through 24 hours. The other outcome measures and the specific analyses are not reported in the registry record. It is also not reported whether the study used a prespecified hierarchy of outcomes or a multiplicity adjustment.
In general, when several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is interpreted without accounting for the number of analyses. A prespecified primary outcome can help distinguish the main question from supporting analyses, but it does not by itself resolve multiplicity across all tests. Without the analysis plan and numerical results, it is not possible to judge how multiplicity was addressed or how it affects interpretation.
The primary analysis population required treatment and complete urine samples at baseline and 24 hours. The registry does not report how many treated participants lacked complete samples, why any samples were incomplete, or how missing data were handled beyond defining the population for analysis. It does not report whether participants with incomplete samples were excluded from other analyses, whether imputation was used, or whether sensitivity analyses assessed the effect of missingness. These details are important because an analysis restricted to complete measurements may represent a different subset from all treated participants.
The record does not report a full statistical analysis plan, the timing of its finalization, interim analyses, or a sample-size justification. Those omissions should not be taken to mean such procedures were absent. They mean that their use cannot be confirmed from the registry record. The planning illustration described in the record is separate from a trial-specific justification and is not evidence of observed power.
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 |
|---|---|---|---|
| Normal Renal Function | 0 | 8 | 0.0% |
| Mild Renal Impairment | 0 | 8 | 0.0% |
| Moderate Renal Impairment | 0 | 8 | 0.0% |
| Severe Renal Impairment | 0 | 8 | 0.0% |
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 |
|---|---|
| Normal Renal Function | 0 of 8 |
| Mild Renal Impairment | 0 of 8 |
| Moderate Renal Impairment | 2 of 8 |
| Severe Renal Impairment | 0 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | 0 of 8 | 0 of 8 | 1 of 8 | 0 of 8 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 8 | 0 of 8 | 1 of 8 | 0 of 8 |
The registry reports zero serious adverse events in each of the four renal-function groups. It reports zero other adverse events in the normal renal function, mild renal impairment and severe renal impairment groups, and two other adverse events in the moderate renal impairment group. The record does not provide the terms or descriptions for those two events. The list of serious-event terms is empty, and deaths are not reported in the registry record; an unreported death count should not be read as zero.
In general, adverse-event counts are descriptive. They record events under the registry's classification and reporting conventions; they do not, by themselves, establish that an event was caused by treatment. The serious-event counts also do not describe the nature, timing or duration of events, and the record does not supply enough detail to assess those features.
The registry lists eight participants at risk for serious events and eight at risk for other events in each group. These safety figures do not substitute for the missing primary endpoint estimates, and they should not be treated as a randomized comparison across renal-function categories. The small group-level counts and the absence of event descriptions limit what can be concluded from the safety record.
12. What the Result Does, and Does Not, Mean
This study addresses a focused question: how pharmacokinetic, pharmacodynamic and safety observations after a single 25 mg dose of BI10773 relate to renal-function category in Japanese patients with type 2 diabetes. Its primary endpoint is total UGE change through 24 hours. The registry record makes that question and endpoint identifiable, but does not report the numerical primary result. As a result, it cannot establish the observed size or direction of the UGE change, or the precision of that estimate.
The record also does not report numerical comparisons between the renal-function groups. A comparison would need to be interpreted in the context of the non-randomized design, because renal-function status defined group membership rather than random assignment. The available description does not show whether measured differences between groups were adjusted for, or how any remaining differences might influence the estimates.
The registered objectives extend beyond the primary pharmacodynamic endpoint to pharmacokinetics and safety. Numerical pharmacokinetic results and details for the other outcome measures are not reported in the registry record. The safety record gives serious and other adverse-event counts, but the event descriptions and death counts are not reported. These data do not support a broad conclusion about safety or about clinical outcomes.
In general, a single-dose Phase I study is designed to characterize responses under a defined exposure and study setting. Its findings, even when fully reported, would not by themselves establish effects under different dosing schedules, in other populations, or over longer follow-up. The registry record does not supply enough outcome results to make even a quantitative assessment within the studied setting.
The most defensible interpretation is therefore limited: the registry records a completed, open-label, non-randomized study and specifies its primary measure and analysis population. It does not report the numerical primary outcome needed to judge the observed response or its uncertainty. No treatment-effect conclusion, clinical recommendation, or comparative claim should be inferred from the endpoint definition alone.
13. Why This Trial Matters Statistically
The study is statistically notable because it frames renal impairment as a source of variation in pharmacokinetic, pharmacodynamic and safety observations after a single dose. Rather than randomizing participants to competing treatments, it compares groups defined by renal-function category. This makes the study useful to examine as an example of how design affects the interpretation of clinical comparisons: group differences are not automatically attributable only to the characteristic used to define the groups.
The primary outcome also illustrates the importance of matching an estimand to a measurement process. Total UGE change is a continuous pharmacodynamic endpoint, and the registered analysis requires complete urine samples at baseline and 24 hours. That definition identifies both what is measured and which treated participants qualify for the primary analysis. At the same time, it raises practical questions about incomplete collection and missing measurements, for which the registry record does not report handling details.
The statistical summary is identified as a least-squares mean with a 95% confidence interval. Those labels communicate the intended form of the result, but not its value or the model that produced it. Without the estimate, interval limits, group contrasts and model details, readers cannot assess magnitude, precision or adjustment. This demonstrates why a registered endpoint and a completed study are not substitutes for numerical results.
The record's planning illustration is also distinct from the study's original design justification. It is described as a calculation based on an observed effect under stated assumptions, not as observed power. Keeping that distinction clear prevents a retrospective planning exercise from being mistaken for evidence about the reliability of the completed study's findings.
More broadly, the record highlights the value of transparent reporting across the full analysis chain: the outcome definition, analysis population, missing-data handling, model, group contrasts, uncertainty and safety-event descriptions. Where those elements are not reported, readers can describe the design but cannot independently evaluate the numerical findings.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting this study from the registry record is that numerical primary-outcome results are not reported. The registry specifies the endpoint and its summary format, but gives no least-squares mean, confidence limits or group comparison. This prevents assessment of effect magnitude, direction and precision. Numerical results for the other outcome measures are also not reported, although the record lists three outcome measures and six analyses.
The design is open-label and non-randomized. Renal-function categories form the study groups, so any comparison is not protected by random allocation. Other participant characteristics may vary across those groups, and the registry record does not describe covariate adjustment or provide information that would allow group comparability to be assessed. The arm descriptions also use “medium dose” for all four groups, while the official title specifies a single 25 mg dose; the record does not clarify the arm-label wording.
The primary analysis requires complete urine samples at baseline and 24 hours. The record does not report the number of participants with complete samples, the reasons for incomplete samples, or any methods used to address missing data. Collection and quality-control procedures are not reported. These omissions restrict assessment of selection into the analysis population and the reliability of the urine measurement.
Statistical details are limited. The model underlying the least-squares mean, the specific contrasts, assumptions, multiplicity approach and sensitivity analyses are not reported in the registry record. Safety information is also brief: adverse-event terms are not provided, and deaths are not reported. These are reporting limitations; they do not establish that the procedures or data were absent from the study itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Renal Impairment Study of Empagliflozin (BI10773) in Japanese Patients With Type 2 Diabetes — NCT01581658.
- Registry record last updated 2017-08-14; status last verified 2017-07.
- Results first posted 2014-06-17.
- 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
NCT01581658 is a completed Phase I, open-label, non-randomized, parallel-group study sponsored by Boehringer Ingelheim. It enrolled 32 Japanese patients with type 2 diabetes and examined a single 25 mg dose of BI10773 across normal renal function and mild, moderate and severe renal impairment groups. The recorded start date is 2012-04-01, with primary completion on 2012-11-01.
The primary outcome was change from baseline in total UGE through 24 hours, summarized as a least-squares mean with a 95% confidence interval among treated patients with complete urine samples at both time points. Numerical primary-outcome estimates and confidence limits are not reported in the registry record. The record reports zero serious adverse events in each group and two other adverse events in the moderate renal impairment group; event terms and death counts are not reported.
The non-randomized design, incomplete reporting of statistical methods and absent numerical efficacy results limit interpretation of group differences. The record supports a description of the study question and design, but not a quantitative conclusion about the primary endpoint.