A Study to Investigate the Effect of Food With Mirabegron in Healthy Chinese Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Investigate the Effect of Food With Mirabegron in Healthy Chinese Participants (NCT04501640), a randomized phase 4 study. The primary outcome is Area Under The Concentration-Time Curve (AUC) From The Time of Dosing Extrapolated to Time Infinity (AUCinf) For Mirabegron.

2. Clinical Question

The central statistical contrast is between fed and fasted administration, not between mirabegron and a different drug. The same participants were scheduled to receive both conditions in different periods, so the design is a crossover rather than a parallel-group comparison. The posted summaries show AUCinf geometric means for each dose and condition, along with geometric least-squares mean ratios and 90% confidence intervals for the fed/fasted pairs.

The registry identifies AUCinf as the primary outcome and number of participants with adverse events as a secondary outcome. The main question is therefore pharmacokinetic: whether the reported exposure summaries differ by food condition, and how precisely the ratio estimates are reported. The registry record does not report a clinical efficacy question or a clinical outcome.

3. Trial Design

The registry describes a Phase 4, open-label, randomized, two-way crossover study of single oral doses of mirabegron. Participants received fed and fasted administrations in either order. The listed sequences were 25 mg fed followed by 25 mg fasted, 25 mg fasted followed by 25 mg fed, 50 mg fed followed by 50 mg fasted, and 50 mg fasted followed by 50 mg fed. The arm descriptions state that a washout period of 10 days was maintained between administrations.

Enrollment was 24. The posted pharmacokinetic summaries report 12 for each dose-condition group. In a crossover, treatment condition is experienced in separate periods, and sequence indicates which condition comes first. Thus the fed and fasted summaries are not equivalent to summaries from independent parallel groups. The record does not report the allocation procedure beyond randomized allocation, nor does it report details of the randomization sequence or concealment.

The study was open-label, meaning masking was listed as none. The primary pharmacokinetic analysis set is defined as participants who received at least one dose of investigational product and had concentration data that allowed derivation of at least one primary pharmacokinetic parameter. The registry reports the sampling schedule as predose and postdose time points through 96 hours on Day 1 of each period.

The study began on 2020-09-21, had primary completion on 2020-10-14, and is listed as completed. Further details about period effects, sequence effects, handling of carryover, and the analysis model 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.

Before assignment: Healthy Chinese female and male participants between 18 to 45 years of age, inclusive (at screening), and met all of the inclusion and none of the exclusion criteria were eligible to participate in this study.

Period 1 (5 Days)

Washout Period (10 Days)

Period 2 (5 Days)

Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic analysis set (PKAS) consisted of all participants who received at least 1 dose of investigational product (IP) for which concentration data were available to facilitate derivation of at least 1 primary pharmacokinetic parameter.

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: All randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Area Under The Concentration-Time Curve (AUC) From The Time of Dosing Extrapolated to Time Infinity (AUCinf) For Mirabegron, measured over Day 1: predose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72 and 96 hour(s) postdose of each period.

The primary endpoint was area under the plasma concentration-time curve from dosing extrapolated to infinity, abbreviated AUCinf. It was reported in hour*nanogram per milliliter (h*ng/mL), as a geometric mean with geometric coefficient of variation. Concentration samples were scheduled from predose through 96 hours after dosing in each period.

AUC describes exposure across time rather than concentration at one moment. AUCinf includes the measured concentration-time information and an extrapolated portion after the last measured time point. This can provide a summary of overall exposure after a dose, while relying partly on an estimate beyond the observed sampling window. The registry description says that AUCinf was derived from plasma samples; it does not report the specific extrapolation procedure or the proportion of the estimate attributable to extrapolation.

For a food-effect question, comparing AUCinf under fed and fasted conditions assesses whether the exposure summaries differ by condition. Geometric means and ratios are often used for pharmacokinetic measures because such values can be skewed and effects are commonly expressed multiplicatively. That is general statistical context, not a claim about the unreported analysis choices for this study. The registry lists geometric least-squares mean ratios for the fed/fasted dose pairs, but does not report a p-value or a decision threshold for interpreting those ratios.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the geometric mean summarize? A geometric mean describes a central value on a multiplicative scale. General statistical context: it is obtained by taking the mean on a logarithmic scale and returning to the original scale. This approach can be useful when measurements are positive and variation is more naturally understood proportionally than as an additive distance. The registry reports geometric means for AUCinf, but does not report whether the analysis used a logarithmic transformation or its exact computational details.

What does a geometric coefficient of variation convey? The geometric coefficient of variation is a measure of relative spread around geometric-scale data. It is distinct from an arithmetic standard deviation. A larger value indicates greater relative variability in the reported measure, but it does not identify the shape of the distribution or describe each participant's result. The registry lists this dispersion measure for all four dose-condition summaries.

How should the ratio be read? A ratio compares two quantities on a multiplicative scale. A value of 100 is the equal-value point when a ratio is expressed as a percentage of the reference; however, the registry does not specify whether that is the scale used for its reported values. The ratio results should therefore be quoted on the scale as posted, without converting them or assigning an unstated unit. The group ordering in the registry is fed then fasted, and the analysis labels the estimates geometric least-squares mean ratios.

What does a confidence interval add? A confidence interval is an uncertainty interval for an estimated quantity under the assumptions of the analysis. General statistical context: a 90% confidence interval is generated by a procedure that, across repeated samples under its assumptions, would cover the target quantity in 90% of such intervals. It is not a probability statement that the fixed true value has a 90% chance of lying within this particular interval. The registry reports 90% intervals for both ratios. The interval width conveys precision on the reported scale, but its validity depends on the analysis model and data assumptions, which are not fully described in the registry record.

Why does the crossover structure matter? In a crossover study, a participant can receive both conditions in separate periods. General statistical context: comparisons can account for within-participant pairing, which may reduce variation when a participant's measurements under the two conditions are correlated. The comparison also needs suitable handling of period and sequence structure. The registry identifies a two-way crossover and lists the treatment sequences, but does not report enough model detail to establish how pairing, period, sequence, or possible carryover were handled statistically. The 10-day washout is stated in the arm descriptions; that alone does not establish how carryover was assessed.

What does a single-dose pharmacokinetic endpoint capture? AUCinf is an exposure summary based on concentrations collected over time, with the endpoint extending from dosing to infinity through extrapolation beyond observed sampling. General statistical context: an extrapolated tail can add uncertainty, especially when the measured concentrations provide limited information about the later part of the curve. The registry does not report the extrapolation method, terminal-phase criteria, or the amount extrapolated for these results. The sampling schedule is listed through 96 hours in each period.

What can be said about significance and multiplicity? No p-values are reported for the two AUCinf ratios, and no multiplicity procedure or family of hypotheses is described in the registry record. A confidence interval can be interpreted as an estimate with uncertainty, but it does not replace a prespecified decision rule. The record does not report a threshold for equivalence or a formal criterion for declaring a food effect. Without those details, the posted estimates should not be reframed as a hypothesis-test conclusion.

How do planning illustrations differ from observed results? Sample-size planning is a design exercise, not a trial outcome. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of the observed effect. Such illustrations do not establish observed power and are not evidence about the study's actual design justification. The registry's own sample-size justification is not reported in the registry record. A planning illustration cannot substitute for the confidence intervals around the observed pharmacokinetic estimates.

What about missing data and analysis populations? The primary pharmacokinetic analysis set is defined by dose receipt and availability of concentration data sufficient to derive at least one primary parameter. This definition does not state how missing samples, incomplete periods, or unusable profiles were handled. The registry does not report sensitivity analyses for missing data. General statistical context: missingness can affect a comparison if the availability of observations is related to condition or outcome, but the record does not provide information to assess whether that occurred in this study.

10. Analyses Reported by the Sponsor

The registry reports geometric least-squares mean ratios for AUCinf: 57.06 with a 90% confidence interval from 46.21 to 70.47 for the 25 mg fed/fasted pair, and 61.42 with a 90% confidence interval from 52.06 to 72.47 for the 50 mg fed/fasted pair. These are the posted inferential estimates, distinct from the geometric mean summaries for each dose-condition group.

A corresponding unadjusted recalculated comparison is not reported in the registry record. The registry reports no p-values for these ratios, and the analysis method is not stated. The registry entries do not support an independent calculation of a replacement ratio or interval. No discrepancy is flagged between the registry analyses and a recalculation. The reported estimates should therefore be read as the registry's analyses, without presenting the group summaries as if they were an adjusted or paired recalculation.

The record does not report enough detail to determine the model behind the least-squares means or how crossover features were incorporated. As a result, the ratios should be interpreted as the estimates reported, with their confidence intervals and stated limitations, rather than as a fully reproducible analysis from the posted summaries alone.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists AUCinf as the primary outcome and number of participants with adverse events as a secondary outcome. It also reports two AUCinf ratio analyses, corresponding to the 25 mg and 50 mg dose pairs. The registry record does not report whether the study had additional prespecified primary or secondary hypotheses, how many comparisons were planned, or whether any multiplicity adjustment was used.

Multiplicity concerns arise when several hypotheses are examined: even if each test uses a fixed error rate, the chance of at least one false-positive result across a family of tests can increase. General statistical context: methods such as adjustment of significance levels or hierarchical testing can address particular multiplicity goals. No such procedure is reported. Since p-values and a testing plan are also not reported in the registry record, the two intervals should not be treated as proof that a prespecified family-wise criterion was met.

The primary pharmacokinetic analysis set included participants who received at least one dose and had concentration data available to derive at least one primary pharmacokinetic parameter. This identifies an analysis population, but does not describe exclusions, missing observations, or the number of participants with complete data for each comparison. The registry does not report an intention-to-treat analysis population or a sensitivity analysis addressing missing concentration data.

The crossover design also makes period-level completeness relevant. The registry record does not report how a participant with measurements in only one period would contribute, how incomplete concentration profiles were treated, or whether any participants were excluded from a particular ratio analysis. It does not report the handling of protocol deviations, the analysis set for adverse events beyond the group counts, or a missing-data assumption. Those details cannot be inferred from the endpoint definition.

Consequently, the posted estimates can be described, but their robustness to missing data and the impact of multiplicity cannot be evaluated from the registry record. No assumptions about imputation, complete-case analysis, or adjustment should be added.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

For each listed dose-condition group, the adverse-event data report 12 participants at risk for serious adverse events and zero with serious adverse events. The data also report 12 at risk for other adverse events and 2 with other adverse events in each group. Deaths are reported as zero in each group. No serious adverse-event terms are listed.

These are group counts, not evidence that the same people did or did not experience events across the crossover periods. The record does not explain whether adverse events were counted by participant, by treatment period, or under another convention beyond the outcome label of number of participants with adverse events. It does not provide event descriptions for the other adverse events in the registry record, so their type, timing, severity, and relationship to treatment cannot be characterized.

Zero reported serious adverse events and deaths in these groups means that none were recorded in the posted figures; it does not establish that the risk of such events is absent. The record does not report a comparative safety analysis or confidence intervals for these counts. The small group counts and the limited detail make these figures descriptive rather than a basis for a broad safety conclusion.

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

The posted pharmacokinetic results describe AUCinf after single oral doses of mirabegron under fed and fasted conditions in healthy Chinese participants. At each listed dose, the fed-condition geometric mean is lower than the fasted-condition geometric mean in the posted summaries. The registry's geometric least-squares mean ratio estimates and 90% confidence intervals also provide comparative summaries on the reported ratio scale.

Those findings are about pharmacokinetics, not symptom improvement, disease outcomes, long-term use, or clinical benefit. The registry describes a study in healthy participants and does not report a treatment-efficacy endpoint. The results should not be generalized beyond the studied population, doses, single-dose setting, and conditions without additional evidence.

Precision is conveyed by the reported confidence intervals, but their interpretation depends on the analysis method and assumptions. Important details—including the model specification, handling of period and sequence, missing data, and any decision threshold—are not reported in the registry record. The numerical ratios therefore do not, on their own, establish whether a formal criterion for equivalence or a clinically meaningful food effect was met.

The adverse-event figures report zero serious adverse events and deaths, and 2 participants with other adverse events in each listed group. These counts are descriptive and do not establish the absence of risk. The registry does not provide the event terms or further comparative safety analyses in the registry record for this report.

In short, the results summarize exposure under two food conditions and report uncertainty for the dose-specific ratios. They do not provide a complete account of the analysis plan, demonstrate a clinical outcome, or answer questions beyond the study's stated pharmacokinetic and safety scope.

14. Why This Trial Matters Statistically

This study illustrates why a trial's design matters when interpreting a simple-looking treatment contrast. The randomized crossover structure means fed and fasted administration occurred in separate periods, with participants assigned to different sequences. Such designs can support within-participant comparisons, but correct interpretation depends on how period and sequence are handled. The registry describes the design and washout, while the detailed statistical model is not reported in the registry record.

The endpoint is also a useful example of pharmacokinetic summaries. AUCinf condenses concentration measurements over time into an exposure measure and includes extrapolation beyond the sampling window. The geometric means, relative variability summaries, and ratio estimates answer different descriptive questions: central exposure, relative spread, and comparative exposure, respectively. Keeping those summaries distinct prevents group-level descriptions from being mistaken for the inferential comparison.

Confidence intervals add information beyond a point estimate by expressing uncertainty, but they do not provide a full decision rule. The registry posts 90% intervals and no p-values, equivalence bounds, or multiplicity procedure. A statistical reader can report what the ratios and intervals say while remaining cautious about conclusions requiring a prespecified threshold or additional model details.

Finally, the trial shows the limits of interpreting sparse safety counts. Zero serious adverse events in the posted groups is a useful descriptive fact, but it does not establish zero risk, especially without event detail or a comparative analysis. Careful reporting separates the observed counts from broader conclusions about safety and clinical impact.

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.

Several trial-specific details needed to assess the pharmacokinetic estimates are not reported in the registry record. The analysis model, treatment of period and sequence, handling of possible carryover, and method for deriving the geometric least-squares mean ratios are not specified. Although the arm descriptions state a washout period of 10 days, the record does not say how adequacy of washout was evaluated.

The endpoint includes extrapolation to infinity, but the registry does not report the extrapolation procedure, the terminal-phase method, or how much of AUCinf was extrapolated. It also does not report individual concentration profiles or participant-level AUC values in the registry record for this report. These omissions limit independent assessment of the endpoint derivation and variability.

The registry does not report p-values, a statistical decision threshold, equivalence bounds, or multiplicity handling. It is therefore not possible to judge whether the results met a prespecified formal criterion for a food effect or equivalence. The absence of a described analysis plan also limits evaluation of whether the posted ratios align with the originally planned analysis.

The analysis-set definition identifies participants with dose and usable concentration data, but there is no account of missing samples, incomplete periods, exclusions, or sensitivity analyses. The adverse-event data provide counts but no terms for the other events, event timing, severity, or treatment attribution. The registry does not describe a comparative safety analysis.

Finally, this was a single-dose study in healthy Chinese participants. The registry entries do not support extrapolation to other populations, longer-term dosing, or clinical outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Investigate the Effect of Food With Mirabegron in Healthy Chinese Participants — NCT04501640.
• Registry record last updated 2024-11-12; status last verified 2024-10.
• Results first posted 2021-10-29.
• 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

NCT04501640 is a completed Phase 4, open-label, randomized, two-way crossover study of single oral doses of mirabegron in healthy Chinese participants. The registry reports enrollment of 24 and fed/fasted sequences at 25 mg and 50 mg, with a 10-day washout stated in the arm descriptions.

The primary endpoint was AUCinf, reported as geometric means with geometric coefficients of variation. The registry reports geometric least-squares mean ratios with 90% confidence intervals for the 25 mg and 50 mg fed/fasted pairs. It also reports other adverse events in 2 participants per listed group, with zero serious adverse events and deaths in each group.

The registry record does not report the detailed statistical model, p-values, multiplicity procedure, or missing-data handling. The results are pharmacokinetic summaries and descriptive safety counts; they do not establish clinical efficacy or a broader safety conclusion.