This Is A Study Of Bioavailability And Food Effect For Fesoterodine.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for This Is A Study Of Bioavailability And Food Effect For Fesoterodine. (NCT01286454), a randomized phase 1 study. The primary outcome is Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Fesoterodine Metabolite (5-hydroxymethyltolterodine [5-HMT]).

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, open-label, single-dose crossover study. The registry lists an enrollment of 20 and describes the study as comparing 4 mg fesoterodine extended-release bead-in-capsule formulations with a commercial tablet in healthy volunteers. In a crossover design, participants receive more than one treatment across different periods, so comparisons can be made within participants. That general feature can reduce the influence of stable differences between participants, but the record does not describe the treatment sequence, period schedule, washout, or the model used to account for the crossover structure.

The six treatment conditions were 4 mg immediate-release beads in a capsule under fasting conditions; 10%, 15%, and 20% coated extended-release beads in a capsule under fasting conditions; 4 mg extended-release tablets under fasting conditions; and a 10% coated extended-release bead-in-capsule formulation under fed conditions. The 20% coated formulation is listed, but its primary-endpoint mean and dispersion are missing, and the registry notes that some values were missing or not estimable for a two-arm comparison.

The study was open label, meaning masking was not used. The registry identifies Pfizer as sponsor and records the study as completed. It lists study start and primary completion as 2010-12 and 2011-03, respectively. The precise protocol, allocation sequence, number of periods completed by each participant, and handling of treatment-period effects are not reported in the registry record.

The primary endpoint was a pharmacokinetic measure of 5-HMT exposure. Secondary outcomes listed include time to maximum observed plasma concentration (Tmax) and plasma decay half-life. The registry describes a pharmacokinetic analysis population consisting of randomized and treated participants with at least one primary PK parameter in at least one treatment period. Details beyond that description, including the analysis population count for each comparison and how incomplete period data were handled, are not reported in the registry record.

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.

Only the first 6 of 11 groups are shown.

Part I- First Intervention Period

Washout Period (At Least 3 Days)

Second Intervention Period

Washout Period (At Least 3 Days)

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here, the N (number of participants analyzed) is signifying the number of participants contributing to the mean.

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 Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Fesoterodine Metabolite (5-hydroxymethyltolterodine [5-HMT]), measured over 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 24, 30, 36 and 48 hours (hrs) post dose.

The primary endpoint was the area under the plasma concentration-time curve for 5-HMT from time zero to extrapolated infinite time, expressed in ng*hr/mL. AUC is a measure of total exposure over time: the concentration-time curve is integrated from dosing through the observed period, then extended to estimate the remaining exposure after the final measured time. The registry describes this quantity as AUC from time zero to the last time point plus the extrapolated portion from that time point to infinity.

Exposure is commonly used in pharmacokinetic studies to compare how much of a drug-related compound reaches the systemic circulation after different formulations or administration conditions. That makes AUC relevant to a bioavailability question, but it is not itself a measure of symptom change or clinical benefit. The endpoint concerns the metabolite 5-HMT, rather than a clinical outcome in people with overactive bladder.

The registry reports geometric means and standard deviations for the primary endpoint. A geometric mean is often used for pharmacokinetic measurements because such measurements can be skewed; on a logarithmic scale, relative differences are more directly represented. The record does not explain why this summary was selected or give the analysis model. Samples were scheduled from 0 through 48 hours after dosing at the listed time points. The record does not state how the extrapolated portion was estimated in individual participants.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous pharmacokinetic measure, and the registry summarizes it with geometric means and standard deviations. General statistical context: a geometric mean summarizes data on a multiplicative scale, which can be useful when concentrations and exposure values are right-skewed. A standard deviation describes dispersion on the scale used for the reported statistic; it is not a confidence interval and does not show the precision of a treatment comparison by itself. The registry does not explain the transformation or model used for the primary endpoint.

What does the primary comparison estimate?

The sponsor-reported analyses are expressed as ratios of adjusted means. A ratio compares the adjusted average exposure in one condition with that in another, after whatever adjustment was used in the analysis. The registry reports four such estimates and 90% confidence intervals, but does not identify the adjustment variables, the statistical model, or whether the ratios were calculated on a log scale and then transformed. The wording “adjusted means” therefore cannot be expanded into a more detailed account of the analysis without information not reported in the registry record.

General statistical context: a ratio and its confidence interval are most useful when the analysis scale and the target comparison are clear. A confidence interval gives a range of values reasonably compatible with the data and the model; its width reflects statistical uncertainty as well as the amount of observed variability. An interval does not determine clinical or regulatory equivalence without an appropriate prespecified margin. No such margin is reported in the registry record.

Why does the crossover design matter?

General statistical context: a crossover study compares treatments received by the same participants, which can control for stable participant-level characteristics. Valid inference can also depend on treatment order, period effects, and whether enough time separates exposures. The registry identifies the design as crossover but does not report the sequence allocation, period effects, washout duration, or model terms. It is therefore not possible to assess from this record how those design features were incorporated into the adjusted comparisons.

The reported arm summaries list the number of participants analyzed for each formulation. Because these participants took part in a crossover study, the arm counts should not be read as separate parallel groups of different people. The primary analysis population is described as randomized and treated participants with at least one primary PK parameter in at least one treatment period. The exact number contributing to each adjusted comparison and the handling of missing periods are not reported in the registry record.

What can the secondary re-calculations show?

The posted half-life summaries report means and standard deviations. The simple re-calculations compare each selected fasting extended-release bead formulation with the immediate-release bead formulation using unadjusted mean differences. General statistical context: an unadjusted mean difference is a direct subtraction of group means and does not account for covariates, treatment sequence, period effects, or any other model structure. The re-calculated intervals and p-values are therefore descriptive checks based on posted summaries, not substitutes for a sponsor analysis that accounts for the study design.

The re-calculated p-values are unadjusted, meaning they do not account for the multiple comparisons and outcomes in the study. They should be treated as exploratory rather than as confirmatory evidence. The registry does not identify a multiplicity strategy for the reported analyses. A statistically small p-value in an unadjusted comparison does not resolve concerns about multiple testing, model choice, or the limitations of summary-statistic re-calculation.

How should planning illustrations be read?

General statistical context: sample-size calculations describe how many participants might be needed for a future study under specified assumptions. The planning illustrations for the half-life comparisons use fractions of the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They give participants per arm for 80% power and participants per arm for 90% power. These are planning illustrations, not the trial’s original sample-size justification and not observed power. The registry does not report the trial’s own sample-size assumptions or justification. In particular, planning based on an observed effect is sensitive to the observed estimate and should not be treated as an independently established effect size.

General statistical context: over-dispersion means the data vary more than a chosen model expects. If present, it can make standard errors and confidence intervals too small unless the analysis accounts for it. The registry does not provide enough information to determine whether over-dispersion was assessed or relevant to these continuous pharmacokinetic outcomes. The same caution applies to distributional assumptions, outliers, and sensitivity analyses: their treatment is not reported in the registry record.

10. Analyses Reported by the Sponsor

The sponsor’s reported primary analyses compare adjusted means as ratios and include 90% confidence intervals for four pairs of formulations. They cover the fasting immediate-release beads versus the fasting tablet, the fasting 10% extended-release beads versus the tablet, the fasting 15% extended-release beads versus the tablet, and fed versus fasting administration of the 10% bead formulation. The registry does not report p-values for these comparisons or explain the adjustment and model used.

The simple re-calculations in the posted results concern secondary half-life comparisons, expressed as unadjusted mean differences. They are not a re-analysis of the primary AUC comparisons and do not reproduce the sponsor’s adjusted ratio estimates. The two approaches address different endpoints and use different scales and methods, so their estimates should not be compared as if they were competing answers to the same question.

No discrepancy is recorded between a sponsor result and a recalculation. Even so, the secondary recalculations remain approximate, unadjusted summaries and should not displace the sponsor’s reported primary analysis. The absence of full model details means the sponsor analysis cannot be independently reconstructed from the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and 14 analyses, but does not report a multiplicity adjustment or a hierarchy for interpreting the multiple comparisons. It reports four primary-endpoint comparisons and includes secondary outcomes for Tmax and half-life. The re-calculated half-life p-values are unadjusted. General statistical context: when several outcomes or contrasts are tested, the chance of at least one apparently unusual result can increase. A prespecified multiplicity strategy can control how results are interpreted, but no such strategy is reported in the registry record. The unadjusted secondary findings should therefore be treated as exploratory.

Missing-data procedures are not reported in the registry record. The record identifies the pharmacokinetic analysis population as randomized and treated participants with at least one primary PK parameter in at least one treatment period. It does not say how missing samples, incomplete treatment periods, or unavailable parameters were handled, or whether any sensitivity analyses were conducted. The primary-endpoint summary is absent for the 20% coated formulation, whose listed analysis count is 4; the registry also notes that values were missing or not estimable for a two-arm comparison.

The record describes the PK population, but does not provide a complete accounting of participant flow through the treatment periods or the number contributing to every endpoint comparison. Although 20 participants were enrolled, the endpoint-specific counts differ across formulations. The record does not explain the reasons for those differences. It also does not report an interim-analysis plan, stopping rules, or a statistical analysis plan. These omissions limit assessment of the planned analysis, the impact of missing observations, and the robustness of the reported estimates.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety record lists 20 participants at risk for serious adverse events in each of the six treatment conditions and zero participants affected by a serious adverse event in each condition. These are treatment-condition counts in a crossover study; they should not be added as though they represented distinct participants across six separate parallel groups. The registry lists no serious adverse-event terms.

Death counts are not reported in the registry record. The record also lists other adverse events affecting 7 participants in the fasting immediate-release condition, 4 in the fasting 10% extended-release condition, 6 in the fasting 15% condition, 0 in the fasting 20% condition, 4 in the fasting tablet condition, and 6 in the fed 10% condition. These are descriptive counts, and the registry record does not provide further detail about event types, severity, timing, or whether the same participant experienced events in more than one condition.

The absence of reported serious adverse events in these treatment-condition counts does not establish the absence of risk. The study enrolled 20 participants and involved single doses; the safety counts should be read within that scope.

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

The results describe pharmacokinetic exposure to 5-HMT after single 4 mg doses of several fesoterodine formulations in a randomized crossover study of healthy volunteers. The primary summaries and sponsor-reported ratios address how measured exposure varied by formulation and by fed versus fasting condition. They do not measure overactive-bladder symptoms, quality of life, or clinical benefit.

The sponsor-reported confidence intervals communicate uncertainty around adjusted-mean ratios. Without a reported equivalence margin, the intervals cannot establish equivalence or bioequivalence under a specified criterion. The record also omits details of the adjustment model and crossover analysis, which limits independent evaluation of the estimates. The missing primary summary for the 20% coated formulation means the record does not support a complete comparison across every formulation listed.

These findings should not be generalized directly to people with overactive bladder. The study is described as enrolling healthy volunteers, used single doses, and focused on a metabolite’s pharmacokinetic measures. The registry does not report long-term outcomes or clinical efficacy results. The secondary half-life analyses add descriptive pharmacokinetic information, but the recalculations are unadjusted and do not establish a confirmatory secondary conclusion.

In short, the registry record can inform interpretation of the measured exposure comparisons under the specific study conditions. It cannot, by itself, determine clinical effectiveness, establish safety over longer use, or settle formulation equivalence without the relevant prespecified criteria and fuller methods.

14. Why This Trial Matters Statistically

This trial illustrates how pharmacokinetic studies distinguish between a formulation’s measured exposure and clinical outcomes. AUC provides a summary of total exposure to 5-HMT, while the secondary half-life outcome describes a different feature of the concentration-time profile. Comparing these measures can help characterize formulations, but each answers a specific pharmacokinetic question rather than a treatment-effect question.

The crossover design is also statistically important. In general, having participants receive multiple conditions can make within-participant comparisons informative, but interpretation depends on treatment sequence, period effects, and the analysis model. Those details are not reported in the registry record. This makes the record useful for seeing the broad design and estimates while leaving important aspects of the statistical analysis difficult to assess.

The study also shows why a confidence interval should be interpreted in relation to a decision criterion. The registry reports 90% intervals for adjusted-mean ratios, but does not report an equivalence margin. Without that criterion, the estimates and intervals describe relative exposure and uncertainty, but do not alone establish equivalence.

Finally, secondary re-calculations and sample-size planning illustrations answer different questions from the trial’s own primary analysis. The half-life re-calculations are unadjusted, and planning values based on observed effects are prospective illustrations rather than evidence about the study’s achieved power. Distinguishing these roles helps prevent descriptive or exploratory statistics from being read as confirmatory findings.

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 registry record leaves important design and analysis details unspecified. It identifies a randomized, open-label crossover study, but does not report treatment sequences, period structure, washout, or the statistical model used for the adjusted primary comparisons. It also does not describe sample-size justification, missing-data procedures, interim analyses, or a multiplicity strategy. These gaps limit assessment of how well the reported methods reflect the crossover design and how robust the estimates are.

Enrollment was 20, and endpoint-specific counts vary. The 15% coated formulation has 16 participants in the primary summary, and the 20% coated formulation has 4 with no reported endpoint estimate. The record does not explain these differences. The absence of a 20% estimate prevents a complete interpretation across the six listed conditions.

The record reports a single-dose study in healthy volunteers, so its pharmacokinetic findings have limited scope for questions about repeated use or clinical outcomes in people with overactive bladder. Numerical Tmax results are not reported in the registry record, although Tmax is listed as a secondary outcome. The death count is also not reported. The safety data therefore provide only a limited descriptive account, and the available pharmacokinetic results should not be treated as evidence of clinical effectiveness or long-term safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: This Is A Study Of Bioavailability And Food Effect For Fesoterodine. — NCT01286454.
• Registry record last updated 2012-01-26; status last verified 2012-01.
• Results first posted 2012-01-09.
• 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

This completed Phase 1 study was randomized, open label, and crossover, with 20 participants enrolled. It compared single 4 mg fesoterodine doses across immediate-release beads, coated extended-release beads, an extended-release tablet, and a fed bead formulation. The primary outcome was 5-HMT AUC from time zero to extrapolated infinite time. The registry reports geometric-mean summaries and four adjusted-mean ratios with 90% confidence intervals. It also lists Tmax and half-life as secondary outcomes, with detailed numerical results for half-life. Serious adverse events affected zero participants in each listed treatment condition; death counts are not reported. The record does not report key details including the primary analysis model, missing-data methods, equivalence criteria, multiplicity strategy, or sample-size justification.