Sanctura Muscarinic Receptor Antagonist Resists Transport (SMART-II) Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sanctura Muscarinic Receptor Antagonist Resists Transport (SMART-II) Trial (NCT01178827), a randomized phase 4 study. The primary outcome is Cerebral Spinal Fluid Levels of Sanctura XR® at Day 10 Post-dose.

2. Clinical Question

3. Trial Design

This is a Phase 4, randomized, parallel-group trial with single masking. The registry lists enrollment of 20 and a completed study. Its recorded start is 2010-08, and its primary completion is 2011-03. The sponsor is Allergan. The condition listed is overactive bladder. The registry record does not identify who was masked, describe the randomization procedure, or provide the planned allocation ratio; those design details are not reported in the registry record.

Three arms are named. The Sanctura XR® arm received trospium chloride, 60mg once daily for 10 days. The oxybutynin IR arm received oxybutynin immediate release, 5 mg three times daily for 2 days. The oxybutynin IR placebo arm received placebo three times daily for 2 days. The primary endpoint concerns cerebrospinal fluid levels of Sanctura XR® at Day 10 post-dose, among patients who received Sanctura XR®. The posted primary endpoint row records 6 participants for this arm, while the oxybutynin IR and placebo rows each record 0 for that endpoint. Their outcome values are not posted.

The study summary says it evaluates cerebrospinal fluid levels of trospium chloride and oxybutynin immediate release in relation to memory performance in patients with overactive bladder and age-associated memory impairment. Secondary outcomes include plasma drug levels and changes from baseline in total and delayed recall on the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised, up to Day 10. These descriptions identify planned or listed measurements, not evidence that results for them are available. The registry record does not report further detail about treatment sequence, assessment timing beyond the listed timeframes, or the operational conduct of masking.

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: All patients who received Sanctura XR®

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 Cerebral Spinal Fluid Levels of Sanctura XR® at Day 10 Post-dose, measured over Day 10 Post-Dose.

The primary endpoint is the cerebrospinal fluid level of Sanctura XR® at Day 10 post-dose, reported as a mean in nanograms per milliliter with standard deviation as the stated measure of dispersion. Cerebrospinal fluid is described in the registry as the fluid surrounding the spinal cord and the inside of the brain. The samples were drawn from patients who received Sanctura XR®.

This endpoint is used to describe the amount of trospium measured in cerebrospinal fluid after the recorded dosing course. As a concentration measure, it addresses drug exposure in the sampled fluid; it is not itself a memory score or a measure of clinical benefit. The trial summary links drug levels and memory performance as topics of evaluation, while memory outcomes are listed separately among secondary measures.

The posted primary endpoint data do not include a mean or standard deviation. The endpoint row records 6 participants in the Sanctura XR® arm, but the result fields are blank. Consequently, the posted results do not show the observed concentration, its variability, or how precisely it was estimated. No numerical interpretation of the primary endpoint is possible from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes this as a randomized, single-masked, parallel-group trial. It does not describe the specific randomization method, who was masked, or the statistical analysis plan. These details are not reported in the registry record. The study has three named arms, but the primary endpoint is recorded for the Sanctura XR® arm only. The record specifies a mean and standard deviation for that endpoint, rather than a treatment contrast or a model-based estimate.

What does the stated summary measure mean?

General: a mean summarizes the central level of a continuous measurement by averaging its observed values. A standard deviation describes how dispersed individual measurements are around that mean. They answer different questions: the mean describes the sample's typical level, while the standard deviation describes variation among observations. Here, the endpoint is a concentration measured in cerebrospinal fluid at Day 10 post-dose. The registry gives the intended summary format, but does not post either statistic. It is therefore not possible to interpret the concentration or its observed variability.

What can be learned from the participant counts?

The primary endpoint row lists 6 participants for Sanctura XR® and 0 for each of the other arms. The count is useful for understanding the displayed endpoint record, but it does not supply an outcome value. A participant count alone cannot tell a reader the mean concentration, the spread of measurements, or the precision of an estimate. Nor should the zeros in the other endpoint rows be treated as evidence that those arms had no participants in the trial: their separate at-risk counts appear in the safety record. The reason the primary endpoint rows show these counts is not reported in the registry record.

General: uncertainty in a mean depends on the amount of information available and on how variable the measurements are. A confidence interval is one common way to express that uncertainty, but it requires an estimate and a defined analysis. Neither a confidence interval nor the inputs needed to reconstruct one are posted for this endpoint. No interval should be inferred from the participant count alone.

Why is there no treatment comparison to interpret?

The primary endpoint description is limited to patients who received Sanctura XR®. The primary result fields are missing, and no numerical values are posted for the other arms in this endpoint record. A between-arm difference would require observed results for the relevant groups and a specified comparison. The registry record supplies neither. The other displayed content may include calculated tables, plots, or planning illustrations, but the unavailable primary endpoint values cannot support an independent comparison.

General: when groups are compared, an analysis may estimate a difference while accounting for the design and any relevant baseline or repeated-measure structure. The choice of model depends on the outcome and protocol. For a continuous measurement such as concentration, possible approaches vary, but it would be inappropriate to name one as the method used in this trial. The statistical model, covariate adjustments, and handling of repeated measurements are not reported in the registry record.

How should statistical significance be understood?

A p-value, when reported, describes how compatible data are with a specified null model under the assumptions of a test. It is not a measure of effect size or clinical importance. No p-value, test statistic, or analysis is posted for the primary endpoint. Statistical significance therefore cannot be assessed from this record. General: interpretation should consider the estimated magnitude and its uncertainty, not a significance label alone. Here, the estimate and uncertainty are both unavailable.

The sample-size assumptions listed for planning illustrations describe a general framework: two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Such an illustration is not the trial's own design justification and is not observed power. The registry record does not report the trial's sample-size justification. Since no observed primary effect is posted here, the planning assumptions do not supply missing outcome evidence.

The record reports 0 analyses. That means no analysis results are available in the posted results represented; it does not establish what analyses were performed outside the registry. A complete interpretation would require the numerical outcomes and methodological details that are not reported in the registry record. The most defensible statistical reading is therefore to distinguish the endpoint definition, which is recorded, from the analysis result, which is not.

10. Multiplicity, Missing Data and Analysis Populations

The record lists six secondary outcomes in addition to the primary endpoint. These cover plasma levels of Sanctura XR®, oxybutynin, and N-Desethyl-Oxybutynin, along with total and delayed recall changes on the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised. The registry reports 8 outcome measures overall and 0 analyses. No numerical secondary results are posted in the registry record.

When a study examines multiple outcomes, the chance of obtaining at least one apparently notable result can depend on how many analyses are conducted and how they are handled. General: a prespecified multiplicity strategy can help define how results across outcomes should be interpreted. The registry record does not report whether a multiplicity adjustment was planned or used, how outcome priorities beyond the named primary endpoint were set, or whether any interim analyses occurred. Those details are not reported in the registry record, so no adjustment strategy should be assumed.

The primary endpoint result fields are missing, and the record has no posted analyses. A blank result is not equivalent to a zero value, and it does not identify why the result is absent. Whether measurements were not collected, were unavailable, were not estimable, or were omitted from the registry record is not reported in the registry record. The endpoint's stated population is all patients who received Sanctura XR®, but the record does not describe an analysis population beyond that wording.

The registry record also does not describe how missing observations were handled, whether participants were analyzed according to randomized assignment or treatment received, or whether any sensitivity analyses were conducted. These are important distinctions for interpreting results, but no specific approach can be attributed to this trial from the posted information. The absence of these details limits assessment of both the outcome analyses and the potential influence of missing data.

11. 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 non-serious adverse event terms

The adverse-event record reports serious adverse events for each listed group: 0 among 6 participants at risk in the Sanctura XR® group, 0 among 10 at risk in the oxybutynin IR group, and 0 among 4 at risk in the oxybutynin IR placebo group. These are event counts within the recorded at-risk groups. They are not measurements of the primary cerebrospinal fluid endpoint and do not describe memory outcomes.

The record also reports other, non-serious adverse events affecting 5 participants in the Sanctura XR® group, 7 in the oxybutynin IR group, and 2 in the placebo group. These figures are counts, not a comparison adjusted for treatment duration, exposure, or other factors. No serious adverse-event terms are listed in the record. Death counts are marked as null; the number of deaths is therefore not reported in the registry record.

General: safety counts should be interpreted in light of the group sizes, observation period, and the way events were collected and classified. The registry record does not describe event ascertainment procedures or provide further details about follow-up for safety. These counts alone do not establish comparative safety, and they do not replace a full account of event types, timing, severity, or relatedness.

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

The record answers some descriptive questions but leaves the central numerical question unresolved. It identifies the primary endpoint as the mean cerebrospinal fluid level of Sanctura XR® at Day 10 post-dose, measured in nanograms per milliliter, and states that standard deviation is the dispersion measure. It also identifies the population as patients who received Sanctura XR®. However, it does not post the mean or standard deviation. Readers therefore cannot tell what concentration was observed or how variable the measurements were.

The trial record describes three randomized arms and gives the dosing schedules for Sanctura XR®, oxybutynin IR, and oxybutynin IR placebo. It also lists six secondary outcomes focused on plasma levels and memory-score changes. These details clarify the study questions and planned measurements, but outcome descriptions are not findings. No numerical memory results or drug-level results are available in the posted analysis information represented.

General: an observed outcome in a study sample does not, by itself, establish what would happen in a broader population. Statistical interpretation normally considers the size of an estimate, its uncertainty, the design, and the analysis assumptions. In this case, the missing estimate prevents evaluation of magnitude and precision, and the absence of a reported analysis plan prevents assessment of the methods used. The record supports no conclusion about whether any treatment improved or worsened memory, or about comparative efficacy.

The serious adverse-event counts are reported separately and should be read narrowly as the counts and at-risk group sizes shown. They do not resolve the missing primary outcome or establish a broader treatment effect. The study is marked completed, but that status does not mean every result is displayed in the registry. The record is useful for understanding the trial's design and endpoint framework; it does not provide the numerical evidence required to judge the stated primary question.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its outcome framework links a pharmacokinetic measurement with memory assessments. The primary measure is a cerebrospinal fluid concentration, while the listed secondary outcomes include plasma concentrations and changes in verbal and visuospatial memory scores. Keeping these outcomes distinct matters: drug concentration and performance on a memory test are different types of measurements and answer different questions.

The design also illustrates why a registry description and a results record serve different purposes. The description identifies randomized parallel groups, masking, dosing schedules, population, and outcome timing. Those details help readers understand what was intended to be studied. But statistical conclusions require posted outcomes and analyses. Here, the primary endpoint's summary fields are blank and no analyses are listed, so the design cannot be translated into an estimate of the measured concentration or its uncertainty.

General: a small or moderate study can still provide useful information when its measures, populations, and analysis are clearly reported. Conversely, even a clearly described design cannot answer an outcome question when the results are unavailable. Precision depends on the observed data and their variability, not merely on the fact that a study was randomized or completed. The registry record does not report a sample-size justification, so enrollment should not be interpreted as evidence of a particular target precision.

The record further illustrates the importance of transparent reporting about analysis populations, missing data, and multiplicity. Multiple outcomes are listed, but no analysis results or adjustment strategy are described. These omissions constrain what can be learned statistically. The principal contribution of this record for readers is therefore a clear account of the study questions and measurements, alongside a reminder that outcome definitions alone are not outcome evidence.

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 main limitation is that the posted primary endpoint has no numerical result. Although the registry specifies the mean, standard deviation, measurement unit, timeframe, and primary endpoint population, it provides no concentration estimate or measure of dispersion. The primary result fields are blank, and no analyses are listed. This prevents assessment of the endpoint's magnitude, variability, precision, or statistical significance.

The primary endpoint rows show 6 participants for Sanctura XR® and 0 for each of the other arms, whereas the adverse-event record includes at-risk counts for all three groups. The record does not explain this difference in endpoint reporting. It is not possible to determine from the posted information whether it reflects collection, analysis, estimability, or reporting. The listed zeros should not be treated as outcome measurements.

The registry record does not report the randomization method, masking details, statistical model, sample-size justification, analysis populations, missing-data procedures, interim analyses, or multiplicity strategy. It also does not give numerical results for the six listed secondary outcomes. These are limitations of the information available in the record; they do not establish that the corresponding procedures or analyses were absent from the study itself.

The adverse-event summary provides counts but limited context about event collection, duration of safety observation, event classification, and relatedness. Death counts are not reported in the registry record. Consequently, the safety summary is narrow and should not be used to infer comparative safety beyond the recorded counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sanctura Muscarinic Receptor Antagonist Resists Transport (SMART-II) Trial — NCT01178827.
• Registry record last updated 2016-02-26; status last verified 2016-01.
• Results first posted 2012-08-16.
• 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 SMART-II trial is recorded as a completed, Phase 4, randomized, single-masked, parallel-group study sponsored by Allergan. It enrolled 20 participants with overactive bladder. The listed arms received Sanctura XR® (trospium chloride), oxybutynin immediate release, or oxybutynin immediate-release placebo.

The primary endpoint is the mean cerebrospinal fluid level of Sanctura XR® at Day 10 post-dose, with standard deviation specified. The primary result values are not posted in the registry record; the Sanctura XR® endpoint row lists 6 participants, while the other two endpoint rows list 0. Six secondary outcomes are listed, but the record reports 0 analyses.

The safety record lists serious adverse-event counts of 0 in each group and other adverse events affecting participants in all three groups. Death counts are not reported in the registry record. Overall, the record describes the design and outcomes but lacks the numerical results needed to interpret the primary endpoint.