Safety and Efficacy of Oral GKT137831 in Patient With Type 2 Diabetes and Albuminuria: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Oral GKT137831 in Patient With Type 2 Diabetes and Albuminuria (NCT02010242), a randomized phase 2 study. The primary outcome is Albuminuria Absolute Value and Ratio to Baseline by Study Visit and Treatment Group.

2. Clinical Question

The study was designed to evaluate the safety and efficacy of GKT137831 in patients with residual albuminuria. Its registry description identifies UACR as the primary outcome and specifies measurements at weeks 8, 10 and 12 of the treatment period, with baseline defined using measurements from Day-14 and Day 1. The endpoint is expressed in mg/g and summarized using geometric means with 90% confidence intervals.

The registry record does not report a numerical treatment effect, confidence interval, or p-value for the primary outcome. It therefore does not permit a quantitative conclusion about the size or precision of any difference between treatment groups. The clinical question is clear from the design and endpoint description, but the posted results do not supply the outcome estimates needed to answer it statistically.

3. Trial Design

This was a randomized, placebo-controlled, parallel-group Phase 2 study. The registry records quadruple masking, but does not identify the roles of the people who were masked. Enrollment was 136. The study status is completed; the recorded start was 2013-10, and primary completion was 2015-02.

The active-treatment arm received GKT137831 100 mg capsules twice a day. The comparator arm received placebo capsules twice a day. The registry describes the study population as patients with type 2 diabetes and diabetic nephropathy, and its summary emphasizes residual albuminuria despite maximal inhibition of the renin angiotensin aldosterone system. The stated objective was to evaluate the efficacy of oral GKT137831 in this population.

Random assignment is intended to make treatment groups comparable on average, while masking is intended to limit influences on treatment delivery, assessment, and reporting. These are general features of randomized, masked trials; the registry record does not provide details of the randomization procedure, concealment process, or which groups of people were masked. It also does not report the rationale for the planned enrollment or a statistical plan that explains how the sample size was selected.

The registry lists several secondary outcome areas, including glucose metabolism measures, 24-hour albumin excretion, 24-hour urine UACR, and eGFR change by study visit. The availability of these outcome descriptions does not establish that numerical results or inferential analyses are reported for them. The primary endpoint description covers change from baseline over the treatment period, with the end-of-treatment summary based on measurements at week 8, week 10 and week 12.

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

Analysis population for the primary outcome, as defined in the registry: Number of subjects analyzed in the Intent to Treat population who have evaluable results

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.

6. Primary Endpoint

The registry lists the primary outcome as Albuminuria Absolute Value and Ratio to Baseline by Study Visit and Treatment Group, measured over Visit 4 (week -2) to visit 11 (week 12).

The primary endpoint is albuminuria assessed through urinary albumin-to-creatinine ratio (UACR), reported in mg/g. UACR relates urinary albumin to urinary creatinine, offering a way to assess albuminuria while accounting for variation in urine concentration. Albuminuria is relevant to the study because the enrolled population is described as having type 2 diabetes with diabetic nephropathy and residual albuminuria.

The registry defines baseline as the geometric mean of the geometric means of UACR measured on Day-14 (visit 4) and Day 1 (visit 5). The end-of-treatment value is defined as the geometric mean of the geometric means measured at week 8 (visit 9), week 10 (visit 10) and week 12 (visit 11). The endpoint description also refers to UACR from baseline to visits 9, 10 and 11. This approach uses repeated measurements to represent baseline and treatment-period albuminuria rather than relying on a single measurement.

Geometric means are commonly used for measurements that are positive and may be unevenly distributed, because they describe a typical multiplicative level. This is a general statistical explanation, not a claim about the distribution of UACR values in this trial. The registry reports a 90% confidence interval as the dispersion measure, but the numerical geometric means and intervals are not reported in the registry record. Without those estimates, the magnitude and precision of the observed endpoint cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous, ratio-based primary outcome summarized with geometric means and 90% confidence intervals. It describes repeated UACR measurements at baseline and during treatment. The record does not report the numerical endpoint summaries, the treatment contrast, or the statistical model used to compare groups. The explanations below describe general statistical concepts and should not be read as a claim that a particular unreported procedure was used.

What does a geometric mean summarize?

A geometric mean is a measure of central tendency suited to positive values that are better understood on a multiplicative scale. It is often useful when measurements have a right-skewed distribution, because a small number of high values can pull an arithmetic mean upward. On a multiplicative scale, changes can be understood in terms of proportional shifts rather than only absolute differences. These are general properties; the registry record does not report the observed distribution of UACR in this trial or explain why this summary was selected.

The baseline and end-of-treatment definitions combine repeated measurements. Repeated observations can reduce reliance on a single value and can represent a period more broadly. They also raise analytical questions: how measurements were combined, what happened when a visit value was missing, and how variability among repeated measurements was handled. The registry gives the geometric-mean definitions but does not report these additional details.

What does a 90% confidence interval convey?

A confidence interval expresses uncertainty around an estimated quantity under a specified statistical procedure. A narrower interval indicates greater precision than a wider interval, while the interval’s location relative to a null value is relevant to interpreting a comparison. The registry specifies 90% confidence intervals as the dispersion measure for the primary outcome, but does not provide the interval limits or explain whether they describe each group’s geometric mean, a change, or a between-group contrast. The numerical results are not reported in the registry record, so neither precision nor compatibility with a range of effects can be assessed.

Confidence intervals do not show the range of individual responses, and they do not establish that a result is clinically important. Statistical uncertainty and clinical importance are distinct questions. Evaluating clinical importance would require a meaningful threshold or context, which is not reported in the registry record.

Why is the comparison between groups important?

In a randomized trial, the central efficacy question is generally about the contrast between assigned groups, not whether a measure changed within one group alone. Changes over time in either group may reflect many influences, including the course of the condition, measurement variation, or aspects of trial participation. A direct between-group estimate is needed to interpret the randomized comparison. The registry’s primary endpoint title refers to albuminuria by study visit and treatment group, but the posted record does not provide the numerical group summaries or a treatment contrast.

Randomization can support a causal interpretation when assignment, follow-up, outcome measurement, and analysis are appropriately conducted. It does not, by itself, resolve missing outcomes, departures from assigned treatment, or bias from selective reporting. The randomization method and the analysis details needed to evaluate these issues are not reported in the registry record.

How should repeated visits and multiple outcomes be considered?

The primary description includes repeated UACR visits during treatment, while the registry also lists secondary outcome measures. Testing or estimating effects across multiple outcomes, visits, or comparisons can increase the chance of finding an apparently notable result by chance when many statistical tests are conducted. Statistical methods can address this issue through prespecified outcome hierarchies or adjustments, among other approaches. The registry record does not report whether such procedures were planned or used. The outcome descriptions alone do not show how multiplicity was handled.

Repeated measurements from the same participant are generally correlated rather than independent. A statistical model for repeated measurements can account for that dependence, but the choice of model and its assumptions matter. The registry record does not specify whether a repeated-measures model, an endpoint summary comparison, or another approach was used. It would be inappropriate to infer the method from the endpoint wording alone.

What is the role of the analysis population?

The primary population is described as Intent to Treat participants with evaluable results. In general, an intention-to-treat approach aims to preserve randomized group assignment in analysis. The phrase “who have evaluable results” indicates that outcome availability is relevant, but the registry does not state how many participants contributed to the primary analysis or how unevaluable results were handled. The exact analysis population and missing-data assumptions therefore cannot be assessed from this record.

Missingness can affect interpretation when the probability of having an observed outcome is related to participant characteristics or outcomes. Common approaches make assumptions about missing values, and sensitivity analyses can examine whether conclusions change under alternative assumptions. These are general considerations; the registry record does not report a missing-data method or sensitivity analysis for UACR.

What do planning illustrations mean?

Any sample-size planning illustration based on an observed effect is a hypothetical planning calculation, not an observed-power result. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are illustration assumptions rather than evidence about the trial’s original design. The registry does not report the sample-size justification or the statistical plan used to design the trial. Because a numerical primary effect is not reported in the registry record, the trial’s observed effect cannot be evaluated from the available information.

10. Multiplicity, Missing Data and Analysis Populations

The registry names a primary UACR outcome and several secondary outcomes, and the primary description includes repeated treatment visits. Considering multiple outcomes and visits creates a multiplicity issue: the more hypotheses examined, the greater the opportunity for chance findings if results are interpreted without an appropriate plan. Methods such as prespecified testing sequences or statistical adjustments can address this concern. Whether any such method was specified or used is not reported in the registry record.

The outcome record describes the primary analysis population as Intent to Treat participants with evaluable results. It does not report the number included in that analysis, the number with missing UACR measurements, or how missing measurements were handled. A restriction to participants with evaluable outcomes can be informative if outcome availability is related to treatment assignment or participant characteristics. The record does not provide enough information to assess whether that concern arose or how it was addressed.

The registry gives a baseline definition using Day-14 and Day 1 measurements and an end-of-treatment definition using week 8, week 10 and week 12 measurements. It does not report how the geometric summaries were calculated when a measurement was unavailable, whether an imputation method was used, or whether sensitivity analyses tested alternative assumptions. These omissions limit assessment of the analysis population and the robustness of the endpoint estimate.

The registry record also does not report a prespecified statistical analysis plan, multiplicity control, or interim-analysis approach. Their absence from the record is not evidence that none existed; it means those methods cannot be evaluated using the registry information available.

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 1.5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anemia (1.5%), cardiac failure acute (1.5%), non-cardiac chest pain (1.5%), lobular pneumonia (1.5%), pneumonia (1.5%).

The safety record reports 68 participants at risk in each group. Serious adverse events affected 3 participants assigned to GKT137831 and 5 assigned to placebo. Other adverse events affected 33 participants in the GKT137831 group and 42 in the placebo group. No deaths are recorded in either group.

These are descriptive counts, not estimates of a treatment effect. The registry does not provide a statistical comparison, confidence intervals, event timing, duration, or a causal assessment for these counts. It also does not explain in the safety entry whether multiple events in one participant could contribute to event totals differently from participant counts; the figures should therefore be read as the recorded affected counts rather than as a complete account of event episodes.

The registry lists Anemia, Cardiac failure acute, Non-cardiac chest pain, Lobular Pneumonia, Pneumonia, and Urinary Tract infection among the top serious terms, each with a reported frequency of 1.5%. The term list does not assign these frequencies to a particular treatment group. The available information supports a description of the recorded counts, but not a conclusion about comparative safety or the cause of any event.

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

The registry record documents a randomized, masked, placebo-controlled Phase 2 study intended to evaluate oral GKT137831 in patients with type 2 diabetes and albuminuria. It specifies UACR as the primary outcome and describes how baseline and end-of-treatment values were constructed from repeated measurements. These design details clarify what the study set out to measure and how the endpoint was defined.

However, the numerical primary endpoint results are not reported in the registry record. Without group estimates, a treatment contrast, and uncertainty measures, the magnitude, direction, and precision of the primary comparison cannot be determined. The trial’s objective is not evidence of an outcome, and the design does not reveal whether the observed UACR measurements favored either group. No efficacy conclusion follows from the endpoint description alone.

The safety entries offer descriptive counts for serious and other adverse events and record no deaths in either group. They do not provide a comparative statistical analysis or sufficient detail to determine timing, cause, or clinical context. The counts should not be treated as proof that one treatment is safer or less safe than the other.

The registry lists additional metabolic, albuminuria, and eGFR outcomes, but numerical results for those measures are not reported in the registry record. It also does not report the sample-size justification, detailed analysis methods, multiplicity procedures, or handling of missing endpoint values. These gaps constrain assessment of the strength and robustness of any treatment comparison.

In short, the record establishes the trial’s design and the questions it addressed, while leaving the key efficacy estimates unavailable. It does not establish that GKT137831 improved albuminuria, that it failed to do so, or that the groups had equivalent outcomes. Those judgments require outcome estimates and their uncertainty, not just an endpoint definition and trial description.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary measure is a repeated, positive biomarker summarized using geometric means. That combination raises useful questions about scale, distribution, and how repeated measurements are combined. Geometric summaries can be appropriate for positive, skewed measurements, while repeated observations require attention to dependence and missing visits. The registry defines the summaries but does not report the statistical model or the observed values needed to evaluate them.

The endpoint also illustrates why the contrast of interest matters. A treatment question is not answered simply by describing change within each arm; the randomized comparison requires estimates that relate the groups directly. The registry’s primary outcome title refers to treatment group and study visit, but numerical comparisons and confidence intervals are not reported. The resulting gap separates a clearly stated research question from an interpretable numerical answer.

Multiplicity is another important consideration. Several secondary outcome areas and multiple primary-endpoint visits are described. When many outcomes or time points are examined, readers need to know whether analyses were prespecified and how the risk of chance findings was handled. The registry record does not report that information.

Finally, the record illustrates the value of distinguishing design details from results. Randomization, masking, enrollment, and safety denominators describe the study structure; they do not substitute for endpoint estimates. Without the primary results and analysis details, the record is useful for understanding the trial question and some safety reporting, but limited for assessing the magnitude, precision, or robustness of the efficacy 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 most important limitation for statistical interpretation is that numerical primary UACR results are not reported in the registry record. The geometric means and 90% confidence intervals are described, but their values are unavailable. This prevents assessment of the treatment contrast, its direction, and its precision.

The registry describes the primary population as Intent to Treat participants with evaluable results, but does not report the number contributing to the primary analysis or the handling of missing measurements. Although enrollment is recorded as 136 and the safety entries list 68 at risk in each group, those figures do not establish the primary endpoint analysis denominators.

The endpoint combines measurements from Day-14 and Day 1 at baseline and from week 8, week 10 and week 12 at end of treatment. The record does not explain the statistical model, the treatment of incomplete visit data, or whether sensitivity analyses assessed alternative missing-data assumptions. It also does not report a statistical analysis plan, multiplicity procedures, or interim analyses.

The safety record provides affected counts and a list of serious-event terms, but does not report event timing, duration, relatedness, or a comparative statistical analysis. The listed term frequencies are not assigned to treatment groups. These details limit interpretation of the safety information as well as the efficacy information.

These are limits of what the registry record reports, not proof that the methods or information were absent from other study materials. The sample-size justification and the original statistical plan are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of Oral GKT137831 in Patient With Type 2 Diabetes and Albuminuria — NCT02010242.
• Registry record last updated 2025-02-28; status last verified 2025-02.
• Results first posted 2025-02-28.
• 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

NCT02010242 is a completed randomized, quadruple-masked, parallel-group, placebo-controlled Phase 2 study of oral GKT137831 in patients with type 2 diabetes and albuminuria. Enrollment was 136. The active arm received GKT137831 100 mg twice a day, and the comparator arm received placebo twice a day.

The primary outcome was UACR in mg/g, summarized as a geometric mean with a 90% confidence interval. The endpoint description defines baseline using Day-14 and Day 1 measurements and end of treatment using week 8, week 10 and week 12 measurements. Numerical primary results and the treatment comparison are not reported in the registry record.

The safety entries record 3 serious adverse events in the GKT137831 group and 5 in the placebo group, with 68 at risk in each arm; other adverse events affected 33 and 42 participants, respectively. No deaths are recorded. Detailed analysis methods, missing-data handling, multiplicity procedures, and the sample-size justification are not reported in the registry record.