A Study to Evaluate Mirabegron in Pediatric Participants From 5 to Less Than 18 Years of Age With Overactive Bladder (OAB): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Mirabegron in Pediatric Participants From 5 to Less Than 18 Years of Age With Overactive Bladder (OAB) (NCT04641975), a randomized phase 3 study. The primary outcome is Change From Baseline to Week 12/EoT in Mean Number of Micturitions Per 24 Hours for Age Group 5 to <12 Years.

2. Clinical Question

3. Trial Design

The registry describes a Phase 3, randomized, double-blind, multicenter, parallel-group, placebo-controlled study of mirabegron in pediatric participants with overactive bladder. The overall age range was 5 to less than 18 years. The primary efficacy endpoint, however, was specified for the 5 to less than 12 years age group. The study also included participants aged 12 to less than 18 years, and the registry lists safety and pharmacokinetic aims for pediatric participants.

There were 26 participants enrolled in total. The primary endpoint results include 9 participants in the mirabegron group and 10 in the placebo group. Those arm counts are endpoint-specific and are not necessarily the same as the enrollment count: the primary analysis population required at least 1 dose and at least 1 post-baseline measurement. The reasons that some enrolled participants do not appear in these endpoint counts are not reported in the registry record.

For the younger age group, the arm descriptions state that the initial mirabegron dose was 25 mg orally once daily on day 1, based on weight, and that placebo was matched to mirabegron. The registry also describes separate treatment groups for participants aged 12 to less than 18 years. Details beyond the truncated arm descriptions are not reported in the registry record.

The listed study start was 2021-03-15 and the primary completion date was 2023-07-07. The study status is terminated. The reason for termination, the number of sites, and whether termination changed the planned conduct or interpretation are not reported in the registry record. The protocol's sample-size justification, planned interim analyses, and full statistical analysis plan are also not reported in the registry record. The registry identifies the sponsor as Astellas Pharma Global Development, Inc.

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: Standard urotherapy included information on and demystification of voiding function and dysfunction, instruction on voiding habits, lifestyle advice regarding fluid intake, prevention of constipation, recording of symptoms and voiding habits in bladder diaries and support via regular follow-up. Specific interventions included various forms of pelvic floor training, behavioral modification, electrical stimulation, catherization and biofeedback and elements of cognitive behavioral therapy.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis set: All participants who were randomized and received at least 1 dose of study drug and had at least 1 post baseline measurement for mean number of micturitions per 24 hours.

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: Safety Analysis Set (SAF) included all participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to Week 12/EoT in Mean Number of Micturitions Per 24 Hours for Age Group 5 to <12 Years, measured over Baseline, week 12.

The primary endpoint is change from baseline to week 12 or end of treatment in the mean number of micturitions per 24 hours for participants aged 5 to less than 12 years. A micturition was defined as a voluntary act of passing urine; episodes involving incontinence alone were excluded. The daily measure was calculated as the average number of times a participant urinated per day during a 7-day micturition diary period.

Change from baseline describes how the recorded measure at follow-up differs from the baseline measure. Negative changes correspond to a lower mean count at follow-up than at baseline. The registry reports a mean change for each arm and a least-squares mean comparison between arms. The endpoint therefore summarizes a repeated daily behavior over a diary period, rather than relying on a single day's count.

Diary-based frequency is used to quantify one aspect of overactive bladder symptoms in a way that can be compared over time and between randomized groups. It does not, by itself, describe every symptom or experience relevant to participants. The registry lists other outcomes, including voided volumes, incontinence episodes, micturitions, dry days, adverse events, and post-void residual volume.

The primary endpoint analysis used last observation carried forward to impute missing week 12 data. The registry specifies the analysis population as randomized participants who received at least 1 dose and had at least 1 post-baseline measurement for the endpoint. The detailed diary-completion rules and the amount of missing endpoint data are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The sponsor reports an analysis of covariance, or ANCOVA, for the primary comparison. In general, ANCOVA models a continuous outcome while accounting for one or more covariates. Adjusting for prespecified baseline or design variables can improve precision or account for differences in those variables. The exact covariates used in this study are not reported in the registry record, so the adjustment cannot be reconstructed from the registry description.

The reported arm-level statistics are least-squares means, also called adjusted means. In general, these are estimates from a fitted model rather than simple averages calculated directly from every participant's outcome. The posted least-squares mean difference is 2.22. The registry gives the order of the groups as mirabegron followed by placebo, but does not describe the covariate adjustment in enough detail to reproduce that model estimate from the arm summaries alone.

The arm-specific spread is reported as a standard error: 0.89 for each group. In general, a standard error describes the estimated uncertainty of a statistic, such as a mean. It is not the same as the spread of individual participants' outcomes. A standard error generally becomes smaller when an estimate is based on more information, although its size also depends on outcome variability and the analysis model. The endpoint counts are 9 and 10, so the arm summaries are based on relatively small groups and should be interpreted with attention to uncertainty.

The registry reports a 90% confidence interval from -0.15 to 4.59 for the least-squares mean difference. In general, a confidence interval gives a range of estimates compatible with the data and the assumptions of the method at its stated confidence level. It is not a range containing a fixed proportion of individual participant outcomes, and it is not a probability statement about the particular interval after it has been calculated. Here, the interval includes zero and extends to values on both sides of zero, so the direction and size of the between-group difference are uncertain.

The reported p value is 0.121. In general, a p value is calculated under a null hypothesis and measures how inconsistent the observed data are with that hypothesis under the statistical model. It does not measure clinical importance and should not be interpreted as the probability that the result occurred by chance. The registry record does not report the prespecified decision threshold or a complete analysis plan, so the p value is best considered together with the estimate, confidence interval, and study limitations.

The primary analysis used last observation carried forward, or LOCF, to impute missing week 12 data. In general, LOCF replaces a missing later value with the participant's most recent earlier observed value. This approach assumes that the last observed measurement is an adequate stand-in for the missing measurement. That assumption may not reflect the participant's actual later outcome, particularly if the outcome would have changed over time. The registry does not report the amount or pattern of missing data, or sensitivity analyses testing alternative assumptions.

The Full Analysis set was defined as randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement for the primary endpoint. This definition excludes randomized participants without a post-baseline measurement from this endpoint analysis. The numbers randomized, treated, and included in every analysis are not all separately reported in the endpoint description.

The registry lists 17 outcome measures and 13 analyses, while multiple secondary outcomes are described. Testing multiple outcomes or contrasts can increase the chance of observing at least one seemingly notable result when all null hypotheses are true. In general, multiplicity can be addressed through prespecified testing sequences, adjusted significance levels, or other procedures. Whether and how multiplicity was handled is not reported in the registry record. No inference about the secondary outcomes should therefore assume a particular adjustment strategy.

A sample-size calculation is a planning exercise, whereas the trial's endpoint counts are observed data. The planning illustration uses the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect varied as a fraction of the observed effect. These assumptions define an illustrative scenario; they do not establish what the trial originally planned or justify its enrollment. The protocol's own sample-size assumptions are not reported in the registry record. Such illustrations are not observed power and should not be used as evidence that the study had a particular probability of detecting an effect.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Mirabegron (5 to < 12 Years)", "Placebo (5 to < 12 Years)")
n   <- c(9, 10)
m   <- c(-1.62, -3.84)
sp  <- c(0.89, 0.89)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Mirabegron (5 to < 12 Years)  9  -1.620  2.670  -3.672  0.432
CARM  Placebo (5 to < 12 Years)  10  -3.840  2.814  -5.853  -1.827

11. Analyses Reported by the Sponsor

The registry's sponsor-reported comparison is an ANCOVA estimate of the least-squares mean difference: 2.22, with a 90% confidence interval from -0.15 to 4.59 and p = 0.121. The arm-level changes are -1.62 for mirabegron and -3.84 for placebo. These types of summaries are related, but the adjusted ANCOVA estimate is not necessarily identical to a difference calculated directly from unadjusted arm means. The adjustment variables and model details are not reported in the registry record.

No discrepancy is flagged between the sponsor-reported result and the record-based comparison. The sponsor's own analysis is therefore the principal result to interpret; a simple unadjusted recalculation, where available, would not replace the sponsor's model-based analysis. Such a recalculation would be a check based on posted summary statistics, not a reconstruction of the full ANCOVA.

The registry record does not report enough detail to independently reproduce the adjusted estimate or its standard error. In particular, the covariates, model specification, and diagnostic checks are not described. The sponsor's reported confidence interval and p value should be read as the stated inferential results, with those reproducibility limits in mind.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures, including secondary measures of voided volume, incontinence, daytime micturitions, dry days, adverse events, and post-void residual volume. It also lists 17 outcome measures and 13 analyses. Examining multiple outcomes can create multiple opportunities to observe a result that appears notable even when there is no underlying difference. Statistical methods can account for this through prespecified testing sequences or adjustments, but a multiplicity strategy is not reported in the registry record. The p value for the primary comparison should not be assumed to be adjusted for other tests.

For the primary endpoint, the registry says missing week 12 or end-of-treatment data were imputed using last observation carried forward. In general, this carries a participant's last observed outcome forward to stand in for the missing follow-up value. The approach relies on an assumption about what the participant's later value would have been; the registry does not report an evaluation of that assumption. The amount, timing, and reasons for missing data, and any sensitivity analyses, are not reported in the registry record.

The Full Analysis set required randomization, at least 1 dose, and at least 1 post-baseline endpoint measurement. This defines who contributed to the primary endpoint analysis, but it is not the same as including every randomized participant regardless of treatment received or follow-up. The registry does not describe additional analysis populations or provide a complete accounting of exclusions for this endpoint.

The posted primary comparison is limited to the 5 to less than 12 years age group. The overall study covered ages 5 to less than 18 years, but a corresponding primary efficacy estimate for the older group is not reported in the registry record. The registry also does not state whether age-group comparisons or other subgroup analyses were prespecified. These omissions limit assessment of the full statistical plan and the role of each analysis.

13. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: electrocardiogram qt prolonged (100.0%), diffuse axonal injury (50.0%).

The registry reports serious adverse events for each age and treatment group as counts of participants at risk and counts affected. In the 5 to less than 12 years groups, 0 of 11 mirabegron participants and 0 of 12 placebo participants were reported with serious adverse events. In the 12 to less than 18 years groups, 1 of 2 mirabegron participants and 1 of 1 placebo participant were reported with serious adverse events. These are small group counts, particularly in the older age groups, and do not support a precise estimate of comparative risk.

The registry lists Electrocardiogram QT prolonged at 100.0% and Diffuse axonal injury at 50.0% among the serious adverse event terms. The denominator and the relationship between these percentages and the participant-level counts are not reported in the registry record, so the percentages should not be interpreted as rates in the full treatment groups. They are listed terms, not evidence by themselves about causation or comparative risk.

No deaths were reported in any of the four listed groups. The registry also reports other adverse events, but the summary counts do not provide event-level context, timing, severity details, or a complete assessment of causality. Safety counts are descriptive; the small numbers and the terminated study status limit what can be inferred from them.

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

The result describes a specific comparison: change in mean micturitions per 24 hours from baseline to week 12 or end of treatment among participants aged 5 to less than 12 years. The sponsor-reported estimate was a least-squares mean difference of 2.22, with a 90% confidence interval from -0.15 to 4.59 and p = 0.121. The interval includes zero and spans values in both directions, indicating uncertainty about the size and direction of the between-group difference.

The result does not establish whether mirabegron is beneficial or ineffective. A statistical estimate from a small endpoint population is not a treatment recommendation, and the p value alone does not determine the importance of an outcome. The arm means show decreases in both groups, but changes within each group do not by themselves isolate the effect of treatment from other influences, including time, study participation, and measurement variability.

The finding also does not answer every question about overactive bladder. The primary endpoint concerns frequency of voluntary urination, excluding incontinence-only episodes. Other symptoms, functional outcomes, longer-term outcomes, and the experience of individual participants are not captured by that single measure. Although the registry lists outcomes in those areas, their results are not described in the primary comparison.

Interpretation is bounded by the endpoint counts, use of last observation carried forward, and missing details about the ANCOVA model and multiplicity. The registry status is terminated, but the reason is not reported in the registry record. The reported data therefore support a description of the analyzed participants and the uncertainty around their estimated group difference, not broad conclusions about all pediatric age groups or outcomes.

15. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be read through its estimate and uncertainty, rather than through arm-level changes alone. Both groups had negative mean changes, while the sponsor's adjusted comparison was expressed as a least-squares mean difference. The contrast and its confidence interval address the between-group question more directly than the fact that either group's mean changed from baseline.

It also highlights the importance of separating the overall study population from the population attached to a particular endpoint. The study enrolled 26 participants across its pediatric age range, while the primary endpoint concerns the younger age group and includes 9 mirabegron participants and 10 placebo participants. Those are distinct descriptions of study size and analysis population.

Small endpoint groups make precision especially important. The confidence interval ranges from -0.15 to 4.59, illustrating that a point estimate alone can give an incomplete impression of uncertainty. The registry's missing model details and missing-data information further show why an apparently simple result may not be fully reproducible from summary statistics.

Finally, the record illustrates the difference between a sample-size planning illustration and a study's actual design justification. Calculations based on the observed effect can explore hypothetical planning scenarios, but they do not reveal the protocol's original assumptions or the chance that the completed trial would detect a particular effect. Those design details are not reported in the registry record.

16. 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 results apply to participants aged 5 to less than 12 years, not automatically to the full age range of 5 to less than 18 years. Although the registry describes separate groups for older participants, a corresponding primary efficacy comparison for that age group is not reported in the registry record. The primary endpoint counts are 9 and 10, limiting the precision of the group estimates.

The study is listed as terminated, but the reason for termination and its consequences for enrollment, follow-up, or planned analyses are not reported in the registry record. The registry does not state whether the final enrollment matched the planned target or provide the original sample-size justification. Thus, the adequacy of enrollment relative to the intended design cannot be assessed from this record.

The primary analysis used last observation carried forward for missing week 12 data. The extent and pattern of missingness, reasons for missing observations, and results from alternative missing-data assumptions are not reported in the registry record. Without that information, it is difficult to assess how sensitive the estimate might be to the imputation approach.

The ANCOVA estimate is reported, but the covariates and full model specification are not. The registry does not report model diagnostics, the prespecified significance threshold, or a complete multiplicity strategy. Those omissions constrain independent reproduction and assessment of the analysis plan. The posted arm summaries and sponsor comparison remain interpretable as reported estimates, but they do not provide every detail needed for a full statistical audit.

Safety counts are also limited by small numbers, especially in the older age groups. The registry's listed serious adverse event term percentages do not include a clear denominator in the record. No deaths were reported, but the sparse counts do not allow precise comparisons of uncommon events.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Study to Evaluate Mirabegron in Pediatric Participants From 5 to Less Than 18 Years of Age With Overactive Bladder (OAB) — NCT04641975.
• Registry record last updated 2024-11-14; status last verified 2024-10.
• Results first posted 2023-12-28.
• 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.

20. Record Summary

NCT04641975 is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled study of mirabegron in pediatric participants with overactive bladder. The registry lists 26 participants enrolled and a terminated status. The primary efficacy endpoint is change from baseline to week 12 or end of treatment in mean micturitions per 24 hours for participants aged 5 to less than 12 years.

The primary endpoint groups included 9 participants receiving mirabegron and 10 receiving placebo. Their reported mean changes were -1.62 and -3.84, respectively. The sponsor-reported ANCOVA difference in least-squares means was 2.22, with a 90% confidence interval from -0.15 to 4.59 and p = 0.121. The primary analysis used last observation carried forward for missing week 12 data.

The registry lists additional outcomes, including safety measures, but the reason for termination, full model details, protocol sample-size justification, and multiplicity approach are not reported in the registry record.