Trospium Chloride XR in Obese Female Patients With Overactive Bladder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trospium Chloride XR in Obese Female Patients With Overactive Bladder (NCT00932022), a randomized phase 4 study. The primary outcome is Percent Change From Baseline in Urinary Urgency Incontinence (UUI).

2. Clinical Question

The primary measure focused on the daily average number of urinary urgency incontinence episodes. Patients recorded accidental leakage, urgency associated with a void, and urgency severity in a 3-day diary. The registry’s endpoint description places baseline at Week 2 and the final measurement at Week 14; the active-treatment schedule likewise began trospium chloride XR after 2 weeks of placebo. The reported comparison therefore concerns the change across the stated measurement period in the patients included in the endpoint analysis, not every randomized patient. The record lists overactive bladder, obesity, and incontinence as conditions relevant to the study.

3. Trial Design

This was a randomized, triple-masked, parallel-group Phase 4 trial sponsored by Allergan. The registry reports enrollment of 127 and an overall study duration of 14 weeks. The study began in 2009-07, reached primary completion in 2011-12, and is listed as completed. The registry does not describe the details of the randomization sequence, allocation concealment, or the specific parties covered by triple masking.

One arm received placebo orally once daily for 2 weeks and then trospium chloride XR 60 mg orally once daily for 12 weeks. The other arm received placebo orally once daily for 14 weeks. The primary outcome was percent change from baseline in urinary urgency incontinence, assessed at Baseline (Week 2) and Week 14. Four secondary outcomes are listed: urgency severity associated with toilet voids, voided volume, an overactive bladder symptom composite score, and the percentage of patients continent. Numerical results for those secondary outcomes are not reported in the registry record.

The primary endpoint analysis was not described as including all randomized participants. Its stated population consisted of modified intent-to-treat patients who had received at least one dose, with the analysis further restricted to those who completed the study at Week 14 and had available endpoint data. The registry does not report how many randomized participants were excluded from that endpoint analysis or why data were unavailable. It also does not report the original sample-size justification, the planned statistical model, or the trial’s detailed analysis plan. Those omissions limit assessment of how closely the posted endpoint analysis follows the study’s original design.

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: Modified Intent-to-Treat (mITT) defined as all patients who were randomized and received at least one dose of study medication. Analysis below was done on patients from the mITT population who completed the study at Week 14 and who had data available for this outcome measure.

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 Percent Change From Baseline in Urinary Urgency Incontinence (UUI), measured over Baseline (Week 2), Week 14.

The primary endpoint was percent change from baseline in urinary urgency incontinence (UUI). Patients used a 3-day diary to record UUI information, including accidental leakage, urgency associated with a void, and urgency severity. The diary measure was the daily average number of UUI episodes: the sum of UUI episodes over valid diary days divided by the number of valid diary days with at least one valid bladder entry. The measurements were taken at Baseline (Week 2) and Week 14.

Percent change was calculated from the Week 2 and Week 14 mean UUI values. The registry defines a negative percent change as improvement. Using a change measure can make the result interpretable relative to the baseline level, while a diary gives a structured way to record episodes over several days rather than relying only on a single retrospective response. These are general reasons such measures may be used; the registry does not state why this endpoint was selected for this trial.

The endpoint is a continuous measure, and the posted arm summaries are means with standard deviations. The outcome is not a count of all episodes over the full study, nor is it the percentage of patients who became continent. Those are distinct interpretations. The primary analysis included only modified intent-to-treat patients who completed the study at Week 14 and had endpoint data available, so the result describes that analyzed subset.

7. Results Posted in the Registry

• Trospium Chloride XR 60 mg: mean -23.70 versus 57.80 on control; difference -81.50 (95% CI -159.18 to -3.82), standardized effect d = -0.43; z-test p = 0.040.

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: each participant’s outcome is expressed as a percent change, and the arm summaries are means and standard deviations. The posted contrast is a difference between those arm means. A mean gives the arithmetic center of the observed values, while a standard deviation describes how dispersed individual values are around that center. General statistical interpretation should consider both the average and the spread, particularly when the spreads differ substantially between arms.

What does the mean difference represent?

The reported mean difference is -81.5, comparing the trospium chloride XR arm with placebo on the percent-change scale. The arm means are -23.7 and 57.8, respectively. The sign of the difference follows the ordering of those means: a negative value indicates a lower average percent change in the active-treatment arm. Since negative change is defined as improvement, the direction is consistent with a more negative average in that arm. This interpretation is about the recorded endpoint and does not establish that treatment caused the difference.

The difference is expressed in percentage-change units, not as a difference in the original number of UUI episodes. It should not be read as a relative risk, an odds ratio, or the proportion of patients who improved. The registry reports a mean endpoint rather than a responder analysis. It does not report the distribution of individual responses, the proportion with worsening, or how many patients achieved a specified change threshold.

Why can variability matter?

Standard deviations describe observed spread, not uncertainty in the mean itself. The placebo arm’s standard deviation is 275.3, compared with 36.16 in the active-treatment arm. Such a difference in spread can matter because methods that assume similar variability across groups may behave differently when that assumption is not met. The registry does not identify the inferential method or state whether equal-variance assumptions were used.

Percent change also has a mathematical feature worth considering in general: it divides a change by a baseline value. When baseline values are small, a given absolute change can correspond to a large percent change. That can produce skewness or extreme values, depending on the observed data. This is a general property of percent-change outcomes; the registry does not report whether it occurred in these data, whether the values were transformed, or whether robust methods were considered.

What do the interval and p-value add?

The posted interval for the mean difference runs from -159.2 to -3.816. A confidence interval is a range constructed by a statistical procedure to express uncertainty around an estimate. In repeated use of the same procedure under its assumptions, the stated confidence level governs the long-run coverage of such intervals. The registry record does not state the confidence level or describe the procedure used for this interval, so the numeric range can be reported but its construction cannot be fully assessed.

The p-value is reported as unadjusted at 0.04. In general, an unadjusted p-value is calculated without accounting for a family of multiple comparisons. It describes how unusual the observed test statistic, or one more extreme, would be under a specified null model. It is not a measure of the probability that the result is due to chance, and it does not measure the size of the difference. The registry does not report the exact test, model terms, covariates, or any adjustment strategy.

How should recalculated quantities be treated?

Simple unadjusted quantities derived from posted summary statistics can be useful as descriptive checks, but they are not substitutes for the trial’s prespecified analysis. The observed standardized difference is reported as -0.425 in the calculation record, but it is not needed to interpret the endpoint in its original units. The registry does not report a prespecified model against which such an unadjusted calculation can be compared. The sponsor’s own analysis takes precedence if a discrepancy is identified; no discrepancy is flagged in this record.

Statistical significance and precision are related but distinct. A p-value near a conventional threshold may coexist with an interval that spans a broad range of possible differences. Conversely, an estimate can be clinically important but uncertain. The posted estimate, interval, p-value, and unequal spreads should therefore be considered together, while recognizing that the analysis population excludes randomized participants without the required Week 14 completion and endpoint data.

10. Confidence Intervals and Precision

The estimated mean difference is -81.5, and the reported interval extends from -159.2 to -3.816. The entire interval is on the negative side of zero, indicating that the values compatible with this interval procedure point toward a lower mean percent change in the trospium chloride XR arm. The range is broad: it includes values much closer to zero as well as substantially more negative differences. Thus, the direction is more clearly indicated than the exact magnitude.

A confidence interval is a way to represent uncertainty around an estimate, conditional on the method and its assumptions. It is not a range containing a fixed proportion of individual patient outcomes, and it does not mean that every value in the interval is equally plausible. The registry does not report the confidence level or the method used to calculate the interval. That missing information prevents a full evaluation of its coverage properties.

The arm-level summaries reinforce the need for caution in judging precision. The standard deviation is 36.16 in the trospium chloride XR arm and 275.3 in the placebo arm. The placebo arm’s reported interval, from -73.7 to 1400.0, is especially wide. These summaries indicate substantial dispersion on the percent-change scale, particularly for placebo. They do not reveal whether the dispersion reflects a small number of extreme observations, a broadly variable response, or another feature of the data.

The p-value of 0.04 is unadjusted, and its interpretation depends on an inferential procedure that is not described in the registry record. Neither that p-value nor the interval removes uncertainty about missing endpoint data, the restricted analysis population, or the unreported analysis plan. Precision should therefore be understood as precision for the reported comparison under its analysis method, not as certainty about the result in all randomized participants or other populations.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect, rather than a description of the trial’s original design. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers an effect to detect stated as a fraction of the observed effect.

For planning for 100% of the observed effect, the figures are 87 participants per arm for 80% power and 117 participants per arm for 90% power. For planning for 75% of the observed effect, they are 155 participants per arm for 80% power and 207 participants per arm for 90% power. For planning for 50% of the observed effect, they are 347 participants per arm for 80% power and 465 participants per arm for 90% power.

Power is the probability that a specified study design would detect an effect of the stated size under the planning assumptions, if that effect were present. The 80% column means planning for a design with 80% power under those assumptions; the 90% column uses a higher target probability of detecting the specified effect. Smaller effects generally require more participants to detect, which is reflected by the larger planning figures for smaller fractions of the observed effect.

These are prospective planning illustrations derived from the observed result, not observed power for the completed trial. The registry record does not report the trial’s original sample-size assumptions or justification, so these figures should not be treated as evidence about the rationale used to enroll 127 participants. They also rely on a simplified normal-approximation framework and may not capture design features or analysis methods that are not reported.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -81.500; pooled standard deviation σ = 191.586.
2. n = 2 × (1.96 + 0.842)² × 191.586² / -81.500² = 86.7, rounded up to 87 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -81.5                      # observed difference in means
sigma <- 191.585987126842                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(932022)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 87 (80% power), 117 (90% power)
 75% of observed effect: n per arm = 155 (80% power), 207 (90% power)
 50% of observed effect: n per arm = 347 (80% power), 465 (90% power)
power.t.test: 87.7 
Simulated power at n = 87 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary endpoint and four secondary outcomes. The secondary outcomes concern urgency severity associated with toilet voids, voided volume, an overactive bladder symptom composite score, and the percentage of patients continent. Numerical results for those secondary outcomes are not reported in the registry record. The record does not state how many statistical tests were planned, whether additional exploratory analyses were conducted, or whether the primary endpoint was selected from a broader set of outcomes.

Multiplicity arises when several statistical hypotheses are tested. In general, the more comparisons made, the greater the chance that at least one will appear notable under a collection of null hypotheses. Common approaches include adjusting the significance threshold or controlling a family-wise error rate, but no such method is reported for this trial. The p-value of 0.04 is identified as unadjusted, so it should not be interpreted as accounting for a multiplicity procedure.

The primary analysis population was modified intent-to-treat, defined as all randomized patients who received at least one dose. The endpoint analysis then included only patients from that population who completed the study at Week 14 and had available data for the outcome. This is a more restricted group than the stated mITT population. The record does not report the number of patients missing endpoint data, the reasons for noncompletion or missingness, or how missing data were handled. It also does not describe sensitivity analyses testing the effect of missing data assumptions.

The endpoint arm counts are 54 for trospium chloride XR and 49 for placebo. These are the analyzed counts reported for this outcome, not the full enrollment count. Safety counts are reported separately. The registry record does not describe whether the endpoint analysis adjusted for baseline values, stratification factors, or other covariates, nor whether any prespecified subgroup analyses were conducted. Without these details, the reported estimate and p-value cannot be matched to a fully specified analysis plan.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: atrial fibrillation (1.6%).

Serious adverse events were reported for 0 of 64 participants at risk in the trospium chloride XR 60 mg group and 1 of 63 participants at risk in the placebo group. These figures are counts of participants affected, not a comparison of event rates adjusted for follow-up time. The registry lists atrial fibrillation at 1.6% among the serious adverse-event terms. It does not specify an arm for that listed term in the available summary, so the term should not be assigned to a particular group based on this information alone.

Other adverse events were reported for 6 of 64 participants in the trospium chloride XR 60 mg group and 3 of 63 participants in the placebo group. These are separate counts from the serious adverse-event counts. The registry does not provide event descriptions for these other adverse events in the summarized information, nor does it report statistical comparisons for these safety figures.

Deaths are not reported in the registry record; a blank or null death count should not be interpreted as confirmation that no deaths occurred. The safety counts also use different denominators from the primary endpoint analysis, which included 54 participants in the active arm and 49 in placebo. The record does not explain the denominator differences or provide exposure-adjusted safety analyses. These figures describe the posted safety reporting and should not be treated as a complete assessment of risks.

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

The posted endpoint data show a mean percent change of -23.7 in the trospium chloride XR 60 mg arm and 57.8 in the placebo arm. The reported mean difference is -81.5, with an interval from -159.2 to -3.816 and an unadjusted p-value of 0.04. Because the endpoint definition treats negative percent change as improvement, the estimate favors a lower mean change in the active-treatment group on this specific measure. The result describes the analyzed participants and does not by itself establish that treatment caused the contrast.

The estimate does not tell how many individual patients improved, worsened, or experienced no change. An average can conceal variation in individual outcomes, and the large placebo standard deviation of 275.3 indicates considerable dispersion on the reported scale. The outcome is percent change in urinary urgency incontinence, not a direct measure of all overactive bladder symptoms, overall wellbeing, or the proportion of patients who became continent.

The interval communicates uncertainty about the mean difference, but the registry does not state the confidence level or calculation method. The p-value is unadjusted, and the registry does not report whether multiplicity was addressed. The primary analysis also required Week 14 completion and available endpoint data, while the missing-data count, reasons, and handling methods are not reported. These features limit conclusions about the result’s precision and its applicability to all randomized participants.

Four secondary outcomes are listed, but their numerical results are not reported in the registry record. The record also does not provide the original sample-size justification, detailed statistical plan, or enough information to assess all modeling assumptions. The result therefore supports a focused description of the posted primary endpoint comparison, not a complete evaluation of every outcome, analysis, or aspect of the trial.

16. Why This Trial Matters Statistically

This trial illustrates why an endpoint’s scale matters. The primary result is expressed as percent change in a daily average of urinary urgency incontinence episodes, rather than as a raw episode count or a proportion of patients meeting a response threshold. Negative values are defined as improvement, making the sign of the result interpretable, but the percent-change scale can be difficult to assess when arm-level variability is very different.

The contrast is notable not only for its direction but also for the spread of the data. The standard deviations are 36.16 in the trospium chloride XR arm and 275.3 in placebo. When groups have substantially different variability, a reader needs to know which inferential method was used and whether it accommodates that difference. The registry does not report those details. This is a useful reminder that a mean difference and p-value should not be read in isolation from the distributional summaries and analysis method.

The endpoint analysis also highlights the distinction between randomization and the analyzed population. Participants were randomized, but the primary outcome analysis was restricted to those who completed the study at Week 14 and had endpoint data. Without counts and reasons for missingness, the extent to which the analyzed set preserves the comparability created by randomization cannot be evaluated from the registry record.

Finally, the record reports an unadjusted p-value while listing multiple secondary outcomes, without stating how multiplicity was handled. That absence matters for interpreting statistical evidence across a family of outcomes. The result is informative as a posted primary comparison, but interpretation depends on understanding uncertainty, analysis-population selection, and reporting completeness—not just whether the p-value crosses a conventional threshold.

17. 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 endpoint analysis population was narrower than the modified intent-to-treat definition: patients also had to complete the study at Week 14 and have endpoint data available. The registry record does not report how many participants were excluded from this analysis, the reasons for missing endpoint data, or the handling of missing values. This prevents assessment of the potential effect of attrition on the comparison.

The reported standard deviations differ substantially between arms, especially given the placebo standard deviation of 275.3. The registry does not describe distributional checks, the statistical model, or methods to address unequal variance or potentially influential values on a percent-change scale. The interval’s confidence level and calculation method are also not reported, and the precise test underlying the unadjusted p-value is not described.

The registry lists four secondary outcomes but does not report their numerical results. It does not report a multiplicity strategy, the original sample-size justification, interim analyses, or a complete prespecified statistical analysis plan. The trial’s randomized and triple-masked design is recorded, but details of sequence generation, allocation concealment, and who was masked are not reported.

The record also does not explain the differences between the endpoint-analysis counts and the safety denominators, or provide exposure-adjusted safety summaries. Deaths are not reported in the registry record. These limitations restrict the conclusions that can be drawn from the posted summaries and should be kept distinct from the observed arm means and comparison.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Trospium Chloride XR in Obese Female Patients With Overactive Bladder — NCT00932022.
• Registry record last updated 2013-01-21; status last verified 2012-12.
• Results first posted 2013-01-21.
• 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.

21. Record Summary

The completed Phase 4 study randomized 127 obese female patients with overactive bladder in a triple-masked, parallel-group design. One arm received placebo for 2 weeks followed by trospium chloride XR 60 mg for 12 weeks; the comparator received placebo for 14 weeks.

The primary endpoint was percent change from baseline in urinary urgency incontinence, measured using 3-day diary data at Baseline (Week 2) and Week 14. The analyzed endpoint counts were 54 for trospium chloride XR and 49 for placebo. The arm means were -23.7 and 57.8, respectively; the reported mean difference was -81.5, with an interval from -159.2 to -3.816 and an unadjusted p-value of 0.04.

The record lists four secondary outcomes but does not report their numerical results. It also does not report the original sample-size justification, detailed statistical methods, missing-data handling, or a multiplicity strategy. Safety summaries report serious adverse events for 0 of 64 active-arm participants and 1 of 63 placebo participants; deaths are not reported in the registry record.