URO-902 in Female Subjects With Overactive Bladder and Urge Urinary Incontinence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for URO-902 in Female Subjects With Overactive Bladder and Urge Urinary Incontinence (NCT04211831), a randomized phase 2 study. The primary outcome is Change From Baseline at Week 12 in Average Daily Number of Urgency Episodes.

2. Clinical Question

3. Trial Design

This completed, randomized, double-masked Phase 2a study evaluated URO-902 in female subjects with overactive bladder and urge urinary incontinence. The registry lists Urovant Sciences GmbH as the sponsor and an enrollment of 80. Enrollment is the registry’s recorded study enrollment; it should not be treated as the number included in every outcome analysis. The study began on 2019-12-16, reached primary completion on 2021-11-18, and is listed as completed.

The study used two dose cohorts. Participants in Cohort 1 received either a single treatment of URO-902 24 mg or matching placebo; participants in Cohort 2 received either URO-902 48 mg or matching placebo. Both active treatments were described as intradetrusor injections. The registry identifies the model as sequential, but further operational details of that model are not reported in the registry record.

The primary outcome was change from baseline at Week 12 in average daily urgency episodes. The registry also identifies treatment-emergent adverse events and treatment-emergent serious adverse events as a secondary outcome. The study description states that efficacy, safety, and tolerability were evaluated up to 48 weeks post-dose, but the primary endpoint comparison concerns Week 12.

The primary endpoint analysis counts were 21.0 for placebo, 22.0 for URO-902 24 mg, and 21.0 for URO-902 48 mg. Safety counts use different numbers at risk: 26 for placebo, 22 for URO-902 24 mg, and 26 for URO-902 48 mg. The registry record does not explain the difference between these analysis populations in the information, so the endpoint and safety denominators should be kept distinct.

Further details about the randomization procedure, allocation concealment, masking roles, and dose-cohort sequence are not reported in the registry record. Those omissions limit how fully the design can be reconstructed from the record alone.

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: A total of 80 participants were randomized into the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT-E Population. Only those participants with data available at the specified data points were analyzed.

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: Intent- to-treat Exposed (ITT-E) population was defined as all participants who were randomized and treated.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline at Week 12 in Average Daily Number of Urgency Episodes, measured over Baseline (Day 1) and at Week 12.

The primary endpoint was change from baseline at Week 12 in average daily urgency episodes, measured in urgency episodes per day. It describes the difference between a participant’s baseline diary-based average and the average recorded at the Week 12 visit. The registry defines baseline as the last non-missing measurement before study treatment and calculates change by subtracting the baseline value from the post-dose visit value.

An urgency episode was counted when a participant answered “Yes” to the bladder diary question “Need to urinate immediately.” The daily average was calculated from urgency episodes recorded on completed diary days within the visit window, divided by the number of days with at least one completed diary day. If more than one diary was completed on a day, the episodes were combined. These rules make the outcome a diary-based daily average rather than a simple count over the entire follow-up period.

This endpoint is used to quantify change in a symptom relevant to the study population. Because it is expressed as a change from baseline, a negative value indicates that the recorded average at follow-up was lower than baseline. The registry reports least-squares means and standard errors for the arms, and between-arm least-squares mean differences from a mixed model for repeated measures. The endpoint is one measure of symptom change; it does not by itself describe all aspects of efficacy, safety, or tolerability.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a repeated measurement of a diary-based symptom, assessed from baseline through follow-up. The registry reports that the comparison was analyzed using a mixed model for repeated measures. This is a general statistical approach for analyzing outcomes measured at multiple visits, while accounting for the fact that observations from the same participant are related rather than independent.

What the model estimates

The reported arm summaries are least-squares means, also called model-based means. In general, these estimates are derived from a statistical model rather than being only raw arithmetic averages. The registry gives the arm estimates as -1.13 for placebo, -2.43 for URO-902 24 mg, and -3.37 for URO-902 48 mg, with standard errors of 0.74, 0.777, and 0.738, respectively. A standard error describes the estimated sampling uncertainty of an estimate; it is not the spread of individual participants’ outcomes.

The registry’s between-arm results are least-squares mean differences. It reports -1.29 for the placebo and URO-902 24 mg comparison, and -2.24 for the placebo and URO-902 48 mg comparison. These are model-based contrasts, not the raw arm summaries. The registry lists 95% confidence intervals for the contrasts, which convey a range of values reasonably compatible with the model and data under the method’s assumptions. A confidence interval is not a guarantee that the true value lies within that specific interval, nor does it describe the range of individual participant responses.

How to read the p-values

The reported p-values are p = 0.172 for the 24 mg comparison and p = 0.016 for the 48 mg comparison. In general, a p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the model assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the magnitude or clinical importance of a difference. The confidence interval adds information about estimate precision and the range of contrasts compatible with the analysis.

Why repeated-measures methods are used

Repeated measurements from one participant tend to be related. A method that treats all observations as independent can misrepresent uncertainty. Mixed models for repeated measures are generally designed to account for within-participant correlation and can use available repeated observations without requiring every participant to have a measurement at every scheduled visit. That general property does not establish how missing measurements were handled in this specific analysis. Details of the model’s covariance structure, fixed effects, handling of missing data, and any sensitivity analyses are not reported in the registry record.

The primary outcome is an average rate per day, constructed from diary entries and completed diary days. In general, rate outcomes can have variability that differs from what a simple constant-variance model assumes, particularly when observations are uneven or more variable than expected. Over-dispersion means that observed variability exceeds what a chosen model expects; if it is not accommodated, uncertainty estimates may be too small or too large. The registry describes a mixed model for repeated measures for the primary comparison, but details sufficient to assess any modeling of rate-specific distributional features are not reported in the registry record.

Analysis population and interpretation

The registry identifies the primary analysis population as ITT-E and says that only participants with data available at the specified data points were analyzed. The ITT-E label identifies the stated analysis population, but the registry record does not provide further detail about its exact inclusion rules in the information. Nor does it report the number of participants with missing endpoint data, reasons for missingness, or a sensitivity analysis evaluating assumptions about those missing data.

In general, missing-data assumptions matter because the observed participants may differ from those without recorded measurements. A model can produce an estimate using available data, but the reliability of that estimate depends on assumptions about why data are missing and on how the model is specified. The registry record does not report enough detail to determine whether those assumptions were examined or how robust the primary results were to alternatives.

The study reports two placebo comparisons, one for each dose. In general, making multiple statistical comparisons can increase the chance of at least one apparently notable result if no adjustment is made. Whether and how multiplicity was addressed is not reported in the registry record. The available p-values should therefore be understood as the reported results for their individual comparisons, without assuming a particular family-wise adjustment or prespecified testing hierarchy.

Finally, these are model-based estimates from an exploratory Phase 2a study. Statistical significance does not establish clinical importance, and a non-significant result does not demonstrate equivalence. The registry record does not report a threshold for a clinically meaningful change, a detailed prespecified statistical analysis plan, or information sufficient to evaluate all modeling assumptions.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparisons using a mixed model for repeated measures. For URO-902 24 mg versus placebo, the reported least-squares mean difference is -1.29, with a 95% confidence interval from -3.16 to 0.58 and p = 0.172. For URO-902 48 mg versus placebo, the reported difference is -2.24, with a 95% confidence interval from -4.04 to -0.43 and p = 0.016. These model-based results are the appropriate starting point for interpreting the study’s stated comparisons.

A simple recalculation from arm-level summary statistics would be unadjusted and would not reproduce all features of a repeated-measures model. It may therefore differ from the sponsor’s model-based estimate. The registry does not flag a discrepancy between the sponsor analysis and the recalculation. Where a discrepancy is flagged, the sponsor’s own analysis takes precedence; no such discrepancy is indicated for these results.

The arm-level estimates and their standard errors give descriptive context, but they do not replace the model-based contrasts, confidence intervals, and p-values. The registry record does not report enough detail about the full model specification to independently reproduce the sponsor’s analysis from the posted summaries alone.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies the primary endpoint analysis population as ITT-E and states that only participants with data available at the specified data points were analyzed. This describes the data included at those assessment points, but it does not fully explain the analysis population definition or the treatment of participants without observations. The detailed inclusion rules for ITT-E are not reported in the registry record.

Missingness is important for this diary-based endpoint because the daily average is calculated from days with completed diary entries. The endpoint definition explains how completed diary days contribute to the average, but the registry record does not report the extent or pattern of missing diary data, the number of missing Week 12 measurements, or reasons for missingness. The model’s specific missing-data assumptions and sensitivity analyses are also not reported in the registry record. In general, results based on observed data may be affected if the likelihood of missing observations is related to the outcome.

Two dose-versus-placebo comparisons are reported for the primary endpoint. The registry record does not report whether multiplicity was controlled, whether the comparisons followed a prespecified hierarchy, or whether p-values were adjusted. In general, multiple comparisons increase the opportunity for a statistically notable result by chance if considered together. The individual p-values therefore should not be interpreted as though a multiplicity procedure was necessarily applied.

The record lists two outcome measures and two analyses, including the primary outcome and a secondary outcome concerning treatment-emergent adverse events and serious adverse events. Additional details about the statistical plan, interim analyses, sample-size justification, and any prespecified subgroup analyses are not reported in the registry record. Without these details, readers cannot fully assess how the reported comparisons fit within the study’s complete inferential plan.

These gaps do not invalidate the posted estimates, but they limit assessment of robustness and the scope of the statistical claims. The reported intervals and p-values should be interpreted as results from the stated analyses, with uncertainty about unreported missing-data and multiplicity procedures kept in view.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: covid-19 pneumonia (4.5%), cervical radiculopathy (3.8%), acute kidney injury (3.8%), arthralgia (3.8%), fall (3.8%).

The registry reports participants at risk and participants affected by serious adverse events and other treatment-emergent adverse events. For serious events, the counts were 3 of 26 for placebo, 1 of 22 for URO-902 24 mg, and 2 of 26 for URO-902 48 mg. For other treatment-emergent adverse events, the counts were 14 of 26, 10 of 22, and 14 of 26, respectively. No deaths were reported in any of the three groups.

These counts describe the numbers recorded in each group; they are not a test of whether the groups differ. No comparative statistical analysis of these safety counts is reported in the registry record. The at-risk denominators also differ from the primary endpoint analysis counts, so safety counts should not be combined with or substituted for the efficacy analysis populations.

The registry lists serious-event terms including COVID-19 pneumonia at 4.5%, and cervical radiculopathy, acute kidney injury, arthralgia, fall, and non-cardiac chest pain at 3.8% each. These listed percentages do not, by themselves, show whether an event was caused by treatment or whether its risk differs between groups. The registry record does not provide a causal assessment in the information. Adverse event counts are descriptive safety observations, and their interpretation depends on event definitions, follow-up, exposure, and clinical context.

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

The primary result concerns change in average daily urgency episodes from baseline to Week 12. The arm-level estimates were negative in all three groups: -1.13 for placebo, -2.43 for URO-902 24 mg, and -3.37 for URO-902 48 mg. These values indicate lower diary-recorded averages than baseline. The model-based comparison for 24 mg had a 95% confidence interval from -3.16 to 0.58 and p = 0.172; the comparison for 48 mg had a 95% confidence interval from -4.04 to -0.43 and p = 0.016.

The estimates do not establish how important a change would be to participants. The registry record does not report a threshold defining a clinically meaningful difference. It also does not report a direct statistical comparison between the URO-902 doses. Although the arm estimates are numerically different, that alone cannot establish a dose-response relationship or identify a superior dose.

The two placebo comparisons give different levels of statistical precision and evidence against a zero contrast under the reported model. Neither p-values nor confidence intervals determine whether an observed difference is clinically important, durable, or likely to recur in another population. The study is described as exploratory, and the registry record does not report a confirmatory testing plan or multiplicity adjustment.

The safety counts provide descriptive information about reported serious and other treatment-emergent adverse events, including the number at risk in each group and the absence of reported deaths. They do not establish that an event was caused by URO-902, nor do the counts alone establish comparative safety. The registry’s reported follow-up description extends to 48 weeks post-dose, while the primary endpoint is at Week 12; the information does not establish how complete follow-up was for each outcome.

In short, the registry reports a Week 12 symptom-change estimate for each group and model-based comparisons of each dose against placebo. Those results are informative about this study’s recorded data, but they do not settle broader questions about clinical importance, durability, causation, dose differences, or applicability beyond the study population.

14. Why This Trial Matters Statistically

This trial illustrates why an arm’s change from baseline and a treatment-versus-control comparison answer different questions. The posted arm estimates describe change within each group, while the least-squares mean differences address the randomized comparisons against placebo using the reported repeated-measures model. Looking only at active-arm change would not account for the placebo group’s own observed change.

It also shows how precision changes interpretation. The URO-902 24 mg comparison has a confidence interval that includes zero, whereas the URO-902 48 mg comparison’s interval does not. The interval widths convey uncertainty beyond the point estimates, and the results should not be reduced to a simple label based only on a p-value. Neither statistical significance nor its absence answers the question of clinical importance.

The endpoint’s construction is another statistical consideration. It is an average per day based on completed diary days, so the result depends on the diary data available within the visit window and the rules for handling multiple diaries on a day. This makes the endpoint definition central to understanding what was measured. The registry provides those calculation rules, but it does not report the amount or pattern of missing diary data.

Finally, the endpoint and safety summaries use different participant counts. Recognizing distinct analysis populations prevents a common misreading in which safety denominators are assumed to match efficacy denominators. The record also gives limited information about multiplicity and model specification, illustrating how registry results can support a careful reading of the posted analyses while leaving important questions about robustness and the full statistical plan unanswered.

15. 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 endpoint estimates come from relatively small analysis groups: 21.0 participants for placebo, 22.0 for URO-902 24 mg, and 21.0 for URO-902 48 mg. The registry lists total enrollment as 80, but enrollment should not be confused with the number contributing to a particular endpoint analysis. The record does not explain why the endpoint counts differ from the safety counts of 26, 22, and 26 at risk.

The registry reports that only participants with data at the specified data points were analyzed, but does not describe the amount, timing, or causes of missing endpoint data. It does not report the mixed model’s full specification, covariance structure, or sensitivity analyses. These omissions make it difficult to assess the effect of modeling choices or missing-data assumptions on the primary estimates.

The two dose comparisons are reported with confidence intervals and p-values, but multiplicity procedures are not reported in the registry record. The record also does not report a direct comparison between doses, so the separate placebo comparisons cannot establish a dose difference. A clinically meaningful threshold for the primary endpoint is not reported, limiting interpretation of the magnitude in clinical terms.

The study is identified as exploratory Phase 2a. The registry record does not report the sample-size justification, detailed randomization and masking procedures, or a full statistical analysis plan. The posted safety results are counts, without reported comparative tests or causal attribution. These features call for a bounded interpretation of the available results rather than a broad conclusion about benefit or risk.

The study description states that outcomes were evaluated up to 48 weeks post-dose, but the primary result is at Week 12. The information does not establish the completeness or pattern of longer-term follow-up for the outcomes. These limitations are specific to what the registry record reports and should be kept distinct from findings that the record does document.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: URO-902 in Female Subjects With Overactive Bladder and Urge Urinary Incontinence — NCT04211831.
• Registry record last updated 2023-04-20; status last verified 2023-03.
• Results first posted 2023-04-20.
• 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.

19. Record Summary

NCT04211831 is a completed, randomized, double-masked Phase 2a study of URO-902 in female subjects with overactive bladder and urge urinary incontinence. The registry records enrollment of 80 and two dose cohorts, comparing single intradetrusor injections of URO-902 24 mg or 48 mg with matching placebo.

The primary endpoint was change from baseline at Week 12 in average daily urgency episodes. The registry reports mixed-model comparisons with placebo for both doses. The 24 mg comparison had a 95% confidence interval that included zero; the 48 mg comparison had a 95% confidence interval that did not. The registry also reports treatment-emergent adverse event counts and no deaths.

Interpretation is limited by unreported details about missing data, multiplicity, full model specification, and the study’s statistical plan. The results describe the posted analyses and do not alone determine clinical importance, comparative dose effects, or causation for adverse events.