A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk. (NCT06481150), a randomized phase 4 study. The primary outcome is Total Urinary Oxalate Excretion Total Urinary Oxalate Excretion.

2. Clinical Question

3. Trial Design

This was a phase 4 randomized crossover study sponsored by the University of Texas Southwestern Medical Center. Its status is completed, with 18 participants enrolled. The registry record gives a start date of 2024-07-01 and a primary completion date of 2025-09-14. Completion status indicates the study is recorded as completed; it does not supply the missing outcome analysis.

In a crossover design, participants receive more than one study condition in separate phases, allowing comparisons within the same participant. As general statistical context, within-participant comparisons can account for stable differences between people, but interpretation also depends on the treatment sequence, timing, and any carryover between phases. The registry record does not report those protocol details, so it is not possible to assess how the crossover was organized or whether carryover was addressed.

The listed interventions were Tenapanor and placebo, each described as 30 mg twice a day. Each study phase lasted 5 days, with urinary oxalate assessed using collections on days 4 and 5. The record identifies the trial as triple-masked but does not specify which groups of people were masked or how masking was maintained. Randomization procedures, allocation concealment, adherence, withdrawals, and the number of participants completing each phase are not reported in the registry record. Those details matter for evaluating the conduct and interpretation of a small crossover study.

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: 18 volunteers were consented and entered screening. Of these, 4 failed screening and another 4 either withdrew consent or were lost to follow-up. The remaining 10 entered this two-phase, cross-over study and were randomly assigned to one of two study arms.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Healthy adults with no history of kidney stones or kidney disease.

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: Healthy adults with no history of kidney stones or kidney disease.

6. Primary Endpoint

The registry lists the primary outcome as Total Urinary Oxalate Excretion Total Urinary Oxalate Excretion, measured over 2 × 24-h urine collections on days 4 and 5 of each 5-day study phase..

The primary endpoint was total urinary oxalate excretion, recorded as a mean in mg/24-h with standard deviation as the stated measure of dispersion. It was based on two 24-hour urine collections on days 4 and 5 of each 5-day study phase; the two collection values were averaged into one reported value. Thus, the endpoint represents urinary oxalate excretion during the measured phase rather than a direct measurement of intestinal absorption.

The endpoint was chosen to reflect the study's hypothesis that affecting intestinal absorption could change the amount of oxalate excreted in urine. The registry rationale describes phosphate and oxalate as using a shared paracellular absorption pathway and proposes that Tenapanor could reduce dietary oxalate absorption and consequently lower urinary oxalate excretion. This is the rationale under investigation, not evidence that the proposed pathway was affected.

Urinary excretion is an indirect measure for the proposed absorption process, and the registry record does not report a separate absorption measure. Nor does it report a clinical kidney-stone outcome. The primary outcome results themselves are not reported in the registry record, so there is no recorded treatment-phase mean or variability to interpret.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint summary measure?

The registry identifies a continuous outcome and specifies a mean with standard deviation. A mean describes the central value of a set of measurements. A standard deviation describes how spread out individual measurements are around that mean. They answer different questions: the mean concerns the level of the measured outcome, while the standard deviation concerns variation among measurements. Neither is reported numerically for this endpoint in the registry record.

The two 24-hour collections from days 4 and 5 of each phase were averaged to form one value. This means the recorded endpoint is not described as two separate daily comparisons. The averaging procedure is stated, but details such as collection completeness, laboratory methods, and quality-control procedures are not reported in the registry record.

Why does the crossover structure matter?

General statistical explanation: a crossover design measures participants under different study conditions at separate times. Because the same person can contribute measurements in both conditions, a comparison can account for stable individual characteristics by examining within-person changes. Those paired measurements are correlated; treating them as if they came from unrelated people can misstate uncertainty.

Analysis of a crossover study may also need to consider the treatment sequence and period in which a measurement occurred. A lingering effect from an earlier phase can complicate interpretation of a later phase. These are general considerations, not claims about what happened in this trial. The registry record identifies a crossover model but does not report the sequences, period structure, washout arrangements, or statistical handling of period and carryover effects.

What do confidence intervals and significance tests contribute?

General statistical explanation: a confidence interval gives an estimate together with a range that reflects uncertainty under the chosen statistical model. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. A confidence interval around a treatment contrast would help readers judge which effect sizes are compatible with the data, not just whether a test crosses a threshold.

A significance test evaluates the data against a specified null hypothesis and analysis model. Its p-value is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. The registry record reports no confidence interval, p-value, or inferential analysis for the primary outcome. No statistical conclusion can therefore be reconstructed from the registry description alone.

How should sample-size planning illustrations be understood?

The stated planning approach describes an illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It defines alternative planning scenarios in terms of fractions of the observed effect. Such estimates are planning illustrations, not observed power and not evidence that the study had a particular probability of finding a result.

Because the primary outcome estimate is not reported in the registry record, the observed effect underlying such planning cannot be evaluated from the record. The registry record also does not report the trial's own sample-size justification, assumptions used at design, or whether planning was based on a clinically important difference. A calculation derived from a small observed effect estimate can be unstable; more generally, planning values depend on the effect, variability, analysis, and design assumptions. Those general cautions do not establish which assumptions were used to design this study.

The record does not report a statistical analysis plan, named analysis method, treatment contrast, or standard error. It is therefore not possible to verify whether the analysis accounted for the within-participant structure or to compare the sponsor's analysis with a simple recalculation. No recalculated estimate is reported, and there is no sponsor analysis to take precedence over one.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, but the record also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The meaning of those categories or time points, and the comparisons they imply, are not reported in the registry record. The recorded outcome description specifies collections on days 4 and 5 and says their values were averaged, but does not explain the multiple categories or time points flagged in the record.

Multiplicity arises when more than one hypothesis or comparison is assessed. As general statistical context, making many comparisons can increase the chance of obtaining a seemingly notable result by chance if the analysis does not account for the number of tests. The registry record does not report a multiplicity adjustment, a hierarchy of tests, or a prespecified primary contrast. With no outcome estimates or analysis results, the impact of multiplicity cannot be assessed.

Missing-data handling is also not reported in the registry record. The record gives total enrollment but not the number with outcome measurements in each phase, withdrawals, reasons for missingness, or methods used to address missing measurements. It does not identify an intention-to-treat, per-protocol, or other analysis population. These omissions prevent assessment of whether participants with incomplete data were included and whether missingness could have affected the treatment comparison.

Randomization, masking, and crossover design are recorded, but procedures for allocation concealment, adherence assessment, and handling of protocol deviations are not reported. Their absence from the record does not establish that the procedures were not used; it means their use and consequences cannot be evaluated from the registry entry.

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.

The registry lists serious adverse events for the Tenapanor and placebo groups. For each group, 10 participants are listed as at risk, with 0 serious adverse events and 0 deaths. The record also lists 10 at risk in each group and 0 other adverse events. These are the posted group counts, not a comparison adjusted for the crossover design.

In a crossover study, a participant may receive both conditions in separate phases. The group-level counts should therefore be read in the context of treatment exposure, not automatically as independent sets of participants. The registry record does not explain how safety observation periods were assigned or how events were attributed across phases. It also does not provide event descriptions, severity beyond the serious/non-serious categories, or exposure duration beyond the stated study phases.

Zero recorded events in these group entries means that no events were listed in those categories for the stated at-risk counts; it does not establish that risk is absent. The safety record does not provide enough detail to assess less common harms or compare safety between conditions with precision. Serious adverse event figures should be interpreted as descriptive registry counts, not as proof of safety or a treatment effect.

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

This trial addresses a focused mechanistic question: whether Tenapanor, compared with placebo, is associated with a change in urinary oxalate excretion during short study phases in healthy adults without a history of kidney stones or kidney disease. The registry rationale connects the proposed intestinal pathway with urinary excretion, but that proposed mechanism remains a hypothesis in the record. Urinary oxalate is the stated endpoint; it is not itself a reported kidney-stone outcome.

The posted information does not include outcome means, variability, a treatment contrast, or an inferential analysis. It therefore does not establish the direction or magnitude of any change, and it cannot show how precisely a difference was estimated. The lack of reported results should not be interpreted as evidence that there was no effect. It leaves the central treatment comparison unanswered in the registry record.

Even if a urinary oxalate comparison were available, general interpretation would depend on design and analysis details, including paired measurements, phase and sequence effects, missing data, and the breadth of the intended population. The registry record does not report enough information to assess these features. The enrolled population is also described as healthy adults, so the stated design does not directly answer questions about people with kidney stones or kidney disease.

The study is recorded as completed, but that status does not substitute for posted results. The record supports describing the rationale, interventions, outcome measurement, and listed safety counts. It does not support claims that Tenapanor reduced oxalate absorption, changed urinary excretion, altered kidney-stone risk, or had a particular clinical benefit or harm.

13. Why This Trial Matters Statistically

The study is statistically notable for combining a randomized comparison with a crossover model and a repeated-measure endpoint. In general, a crossover can make within-person comparisons informative when each participant contributes usable measurements under both conditions and when period and carryover effects are handled appropriately. That structure also makes the analysis different from a simple comparison of unrelated groups. The record does not report enough design or analysis detail to determine how these issues were addressed.

The endpoint is directly tied to the stated biological hypothesis but remains a measurement of urinary excretion. Distinguishing a proposed mechanism from an observed endpoint is important: a rationale can motivate measurement, but only reported data and analysis can show what was observed. Here, the registry record describes the measurement procedure without reporting the outcome estimates.

Small pilot studies can be useful for exploring feasibility and informing later research, but estimates from a small study may be imprecise. This is general statistical context; the registry record does not report a design justification or an uncertainty estimate for this trial. Enrollment is listed as 18, while the safety groups each list 10 at risk. Because the study is crossover and the registry does not explain those counts, they should not be treated as a clear account of completed paired outcome data.

The most important statistical point is the boundary between a completed study record and an interpretable treatment result. Without a reported contrast, uncertainty interval, and analysis description, readers cannot judge effect size, precision, or robustness. The registry entry documents a research question and study structure, but does not provide the evidence needed to answer that question statistically.

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 primary limitation for interpretation is that the registry record does not report the primary outcome results or any analyses. It gives no treatment-phase means or standard deviations, no contrast, and no confidence interval or p-value. Thus the magnitude, direction, and precision of the primary comparison cannot be assessed.

The stated population is healthy adults with no history of kidney stones or kidney disease. The record does not give further participant characteristics, so the enrolled population cannot be described in greater detail. The condition listed is hyperoxaluria, but the stated population should not be conflated with people diagnosed with that condition. No clinical kidney-stone endpoint is listed in the posted outcome description; the primary measure is urinary oxalate excretion.

Important crossover details are not reported in the registry record, including treatment order, period structure, washout arrangements, and handling of sequence, period, or carryover effects. The record also does not report randomization procedures, the roles included in triple masking, adherence, participant flow by phase, or reasons for missing data. These details limit evaluation of both potential bias and the analysis population.

The safety record provides counts but not detailed event descriptions or an explanation of how at-risk counts relate to treatment periods in the crossover. The primary outcome description also contains a record-level note about multiple categories or time points without explaining them. Together, these gaps limit assessment of multiplicity and the completeness of outcome reporting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk. — NCT06481150.
• Registry record last updated 2026-10-07; status last verified 2026-09.
• Results first posted 2026-10-07.
• 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

The registry record describes a completed phase 4, randomized, triple-masked crossover pilot sponsored by the University of Texas Southwestern Medical Center. It lists 18 participants enrolled and a healthy-adult population with no history of kidney stones or kidney disease. The interventions were Tenapanor and placebo, each described as 30 mg twice a day during a 5-day phase.

The primary endpoint was mean total urinary oxalate excretion in mg/24-h, based on two 24-hour collections on days 4 and 5 of each phase and averaged to one value. The registry record does not report the endpoint results, a treatment comparison, or analyses. It lists 0 serious adverse events, 0 other adverse events, and 0 deaths in each group, with 10 at risk per group. These safety entries are descriptive counts and do not resolve the unanswered primary outcome question.