Bioequivalence Study of Esomeprazole 20 Milligram (mg) Delayed-Release Capsules in Healthy Adult Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bioequivalence Study of Esomeprazole 20 Milligram (mg) Delayed-Release Capsules in Healthy Adult Participants (NCT05265247), a randomized phase 1 study. The primary outcome is Maximum Observed Post Dose Concentration (Cmax).

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, single-center, single-dose, two-period, two-sequence crossover study in healthy adult participants. It compared esomeprazole 20 mg delayed-release capsules made by Catalent, Guayama, with the esomeprazole 20 mg delayed-release capsule identified as Nexium 24HR, the reference product. Dosing was under fasted conditions. The study record lists 61 participants enrolled and a completed status. The recorded start date is 2022-03-02, and the primary completion date is 2022-06-02.

In a crossover design, participants receive both products in different periods. Random assignment to treatment sequence helps determine which product is received first. Such designs can support a within-participant comparison, because measurements under the two products come from the same participants, provided the analysis appropriately accounts for the design. The registry identifies two treatment sequences, but the complete sequence descriptions are truncated in the record. Details of washout duration and any procedures to assess carryover are not reported in the registry record.

The masking information is not fully consistent within the registry: the structured masking entry says double, while the official title calls the study single blind. The record does not explain this difference, so the masking arrangement cannot be characterized more specifically. The study record lists gastrointestinal diseases as a condition, but its title and population description identify healthy adult participants; the record does not establish that participants were enrolled as patients with a gastrointestinal disease.

The primary pharmacokinetic analysis group is described as participants who completed both periods and for whom relevant pharmacokinetic parameters were available. The reported Cmax group counts are 44 for each product. These are product-group counts in a crossover study and should not be added as if they represented distinct participants. The record does not give a complete participant-flow account or explain why the primary analysis counts differ from enrollment.

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: A total of 61 participants were enrolled, of which 55 participants were randomized and dosed (6 enrolled participants were not randomized).

Period 1 (2 Days)

Washout Period (7 Days)

Reasons for not completing this period:

Period 2 (2 Days)

Analysis population for the primary outcome, as defined in the registry: PK analysis set included all participants of the PK population who completed both treatment periods, and for which the relevant PK parameters (at least at least Area Under the Plasma Concentration Versus Time Curve Calculated from Time 0 to the Last Measurable Sampling Time Point \[AUC0-t\] or Cmax) could be derived. Participants with baseline concentration greater than (\>) 5 percent (%) of the individual Cmax for either period were to be excluded from the PK analysis set.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety population- comprised all randomized participants who received at least one dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Post Dose Concentration (Cmax), measured over Pre-dose (within 1 hour prior to dosing), 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8,10, 12, 16, and 24 hours post dose in each treatment period (each period is of 2 days).

The primary endpoint is maximum observed post-dose concentration, abbreviated Cmax. It measures the highest concentration of esomeprazole observed in collected blood samples after dosing. The registry specifies that Cmax was obtained without interpolation: the value is the maximum among the observed sampling measurements, rather than an estimated peak between measured time points.

Blood sampling was scheduled before dosing and at multiple post-dose times through 24 hours in each treatment period. The registry says that pharmacokinetic parameters were calculated using standard non-compartmental analysis. Cmax is a concentration measure, reported in nanograms per milliliter, and provides information about the observed peak exposure after a dose. Comparing Cmax between test and reference products is relevant to a bioequivalence assessment because it addresses whether the observed peak concentrations are similar in relative terms.

The registry summarizes Cmax using geometric means and geometric coefficients of variation. A geometric mean is a way to describe the central level of positive measurements when values are treated on a multiplicative scale. The coefficient of variation describes relative dispersion, rather than the spread in the endpoint's original units. Cmax is only one aspect of the concentration-time profile. The registry also lists other pharmacokinetic outcomes, including area under the concentration-time curve, time to maximum concentration, and elimination measures. Their presence does not change the interpretation of the primary endpoint, and their results are not all available in the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents a randomized, two-period, two-sequence crossover comparison. The analysis is reported as a ratio of geometric least-squares means for Cmax, with a 90% confidence interval. The statistical method field for the posted analysis is not specified. The interpretation should therefore focus on the reported estimand and uncertainty rather than assume a particular model or implementation.

Why use a crossover comparison?

General explanation: in a crossover study, each participant receives both products in different periods. This can reduce the influence of stable differences between people, because the comparison can use each participant as their own reference. Randomization of sequence helps balance which product is received first. The benefit depends on the quality of the period design and on an analysis that reflects the repeated measurements within participants. The registry confirms the crossover structure and two sequences, but detailed period procedures, washout duration, and the specific analysis model are not reported in the registry record.

General explanation: a crossover analysis may account for treatment, period, sequence, and within-participant variation, but the record does not say which terms or model were used. It would be inappropriate to attribute a particular model, adjustment, or variance estimator to this analysis based only on the endpoint summary.

What does a geometric mean ratio express?

The reported comparison is a ratio, rather than a difference in concentration units. A ratio expresses the relative level of the test product's geometric least-squares mean compared with the reference product's geometric least-squares mean. A ratio at equality corresponds to the same estimated geometric mean under the two products. A ratio below or above equality indicates the direction of the point estimate. The reported ratio is below equality, and the confidence interval spans equality.

General explanation: pharmacokinetic measurements are often positive and may vary multiplicatively. Geometric summaries can be useful for such data because they describe a central level on a relative scale. A geometric least-squares mean is typically an estimate adjusted according to a statistical model, but the model and any adjustments are not reported in the registry record. The posted group-level geometric means are descriptive summaries and are not a substitute for the reported ratio analysis.

How should the confidence interval be read?

General explanation: a confidence interval conveys the uncertainty around an estimated effect under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval for the same quantity and method. The reported interval is a 90% confidence interval for the ratio. Its inclusion of equality indicates that the posted interval is compatible with equal relative Cmax as well as values on either side. This is not a test of whether the products are equivalent: equivalence requires an explicit margin or range, which is not reported in the registry record.

General explanation: failure to exclude equality in a conventional difference-based test is not the same as demonstrating equivalence. Equivalence asks whether the uncertainty is sufficiently contained within specified limits. Without those limits, the ratio and interval can be described, but the equivalence decision cannot be independently evaluated from the registry record. No p-value is posted for this comparison.

Why does variability matter?

The reported geometric coefficients of variation are 51.1 for the test product and 46.2 for the reference product. A coefficient of variation describes spread relative to the central level, which can be more interpretable than an absolute standard deviation when measurement scale differs. The coefficients indicate that observations vary around the group summaries; they are not confidence limits and do not directly quantify uncertainty in the ratio.

General explanation: over-dispersion means that observed variation is larger than a chosen model expects. If present and not handled appropriately, it can make standard errors and confidence intervals too optimistic. The registry does not report an over-dispersion assessment or a variance model, so no such issue can be diagnosed from the posted summaries alone. The coefficients of variation are descriptive and should not be treated as evidence for or against a particular model assumption.

What can the planning illustration tell readers?

Any sample-size illustration based on the observed effect is a planning exercise, not an observed study result and not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a fraction of the observed effect. Non-time-to-event figures refer to participants per arm. These assumptions do not establish the study's actual design rationale. The registry's own sample-size justification is not reported in the registry record.

In particular, a planning illustration based on an observed effect is sensitive to the estimated effect and to the assumed fraction of that effect. It does not show the probability that the completed trial detected an effect, nor does it replace the confidence interval for the observed comparison. The registry does not report a protocol-based sample-size calculation, interim analyses, or a prespecified statistical analysis plan. Those details should not be inferred from a planning illustration or from the reported outcome summaries.

10. Analyses Reported by the Sponsor

The registry-posted analysis reports a geometric least-squares mean ratio and a 90% confidence interval for Cmax. It is identified as an equivalence analysis, although the method field and equivalence limits are not reported in the registry record. This is the analysis to use when describing the reported inferential result. The product-specific geometric means are descriptive summaries and do not reproduce the paired crossover analysis on their own.

A simple recalculation from posted summary statistics, where available, is not necessarily identical to the sponsor's analysis. It may not preserve the participant-level pairing or model adjustments used in the original analysis. The registry record does not flag a discrepancy between the sponsor analysis and a recalculation. No separate recalculated estimate or interval is reported in the registry record, so a numerical comparison between the two cannot be made from the posted information. If a discrepancy were present, the sponsor's own analysis would take precedence; the record does not indicate one.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary Cmax outcome and five secondary outcomes: AUC from time zero to infinity, the percentage of AUC obtained by extrapolation, terminal elimination rate constant, time to maximum observed concentration, and elimination half-life. The record lists seven outcome measures overall, but not all results are available in the posted material. Values are missing or not estimable for a two-arm comparison for another endpoint. The reason for those missing or non-estimable values is not reported in the registry record.

When multiple outcomes are examined, the chance of obtaining at least one apparently notable result can increase if each is assessed separately. General explanation: multiplicity procedures can control that issue, but whether they are needed and how they are applied depends on the prespecified analysis plan and the role of each outcome. The registry does not report a multiplicity strategy, hierarchy among secondary outcomes, or adjusted decision criteria. The posted analysis count is two, but the record does not explain the analysis set or multiplicity handling for those analyses.

The primary population is described as participants who completed both treatment periods and had relevant pharmacokinetic data. That defines an available-data analysis group, but details of exclusions, missing samples, protocol deviations, or handling of incomplete profiles are not reported in the registry record. The difference between enrollment of 61 and the Cmax product-group counts of 44 is not explained. Because each participant can contribute under both products in a crossover, those product counts should not be summed to infer a number of unique participants.

The registry does not report interim analyses, a missing-data strategy, or a full statistical analysis plan. It also does not explain whether outcome-specific populations differed or how missing concentrations affected endpoint calculations. These omissions limit assessment of selection, multiplicity, and robustness. They do not establish that a particular problem occurred; they mean the relevant procedures cannot be evaluated from the registry record.

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

The posted safety figures list no serious adverse events in either product group and no deaths. For other adverse events, the registry reports 8 affected participants among 48 at risk for the test product and 13 among 51 at risk for the reference product. These are counts for the safety groups recorded for each product. In a crossover design, the group counts need not represent distinct participants, and the registry does not explain the differing numbers at risk.

The record does not provide serious adverse event terms because none are listed, and it does not give event-level detail for the other adverse events in the information summarized. It also does not specify in these figures whether events were judged related to treatment. A count of zero serious adverse events in this study is a description of the observed record, not proof that serious events cannot occur. The safety figures should be read in the context of the study's size, healthy adult population, single-dose design, and available observation period; they do not establish comparative safety beyond those data.

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

The posted result describes a relative comparison of maximum observed concentration after a single dose of two esomeprazole 20 mg delayed-release capsules in healthy adults under fasted conditions. The estimated geometric least-squares mean ratio is below equality, while its 90% confidence interval spans equality. This communicates both the direction of the point estimate and uncertainty around it. The result should not be reduced to the point estimate alone.

The registry labels the analysis as an equivalence analysis, but the acceptable equivalence limits are not reported in the registry record. Without those limits, the displayed ratio and confidence interval cannot establish whether the prespecified equivalence criterion was met. The record also does not report a p-value for the primary comparison. The appropriate statistical reading is therefore descriptive of the estimate and its interval, not a definitive equivalence determination.

The endpoint concerns peak concentration, not every aspect of drug exposure. The registry lists other pharmacokinetic outcomes, but their results are not all available. Cmax results do not, by themselves, describe total exposure, the clinical response to treatment, or outcomes with repeated dosing. The trial enrolled healthy adults and used a single-dose, fasted setting; its findings do not directly describe a patient population or other dosing conditions.

The results do not establish that either product is clinically preferable, nor do they amount to medical advice. They describe the posted pharmacokinetic data and the precision of the reported comparison. Further interpretation would require information not reported in the registry record, particularly the equivalence limits, detailed analysis model, participant flow, and complete secondary outcome results.

14. Why This Trial Matters Statistically

This trial illustrates why the design and estimand matter when reading a bioequivalence result. A crossover comparison uses two treatment periods and two sequences, so the product comparison is not simply a comparison of unrelated groups. The reported geometric least-squares mean ratio is the central inferential quantity, while the product-specific geometric means and coefficients of variation provide descriptive context. Keeping those roles distinct prevents the group summaries from being mistaken for the full crossover analysis.

It also shows why a confidence interval must be interpreted against a decision criterion. The interval communicates uncertainty, but an equivalence label alone does not reveal whether the interval falls within acceptable limits. Because those limits are not reported in the registry record, the posted estimate can be described without claiming that an equivalence decision has been demonstrated.

The record contains practical uncertainties that statistical readers should notice: the title and structured masking entry differ, the complete participant accounting is not reported, and some outcome results are missing or not estimable for comparison. These details affect how fully the design and analysis can be audited. The study is therefore useful as an example of reading estimates, endpoint definitions, analysis populations, and registry completeness together, rather than treating a single result label as a complete account of the evidence.

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 limitations specific to this study constrain interpretation. The registry's official title describes the study as single blind, whereas the structured masking entry says double. The record does not resolve the difference. The treatment-sequence descriptions are truncated, and details such as washout duration and period procedures are not reported in the registry record. These omissions prevent a full assessment of how the crossover was implemented.

The primary outcome population is defined by completion of both periods and availability of relevant pharmacokinetic data, but the reason the Cmax counts are 44 per product when 61 participants were enrolled is not reported. Participant flow, exclusions, missing samples, and protocol deviations are not described in the available record. This makes it difficult to assess the extent and potential effect of missing data or selection into the pharmacokinetic analysis.

The registry does not provide the equivalence margins, detailed statistical model, p-value, or full statistical analysis plan for the primary comparison. It also does not report a multiplicity strategy for the listed secondary outcomes. Results for all listed outcomes are not available, and one endpoint has values that are missing or not estimable for a two-arm comparison. The reasons are not reported in the registry record.

Finally, the study concerns a single dose under fasted conditions in healthy adults. The record does not support extending the Cmax result to repeated dosing, other conditions, or clinical outcomes. The posted safety counts likewise describe only the recorded study groups and do not resolve broader safety questions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bioequivalence Study of Esomeprazole 20 Milligram (mg) Delayed-Release Capsules in Healthy Adult Participants — NCT05265247.
• Registry record last updated 2024-02-05; status last verified 2023-05.
• Results first posted 2024-02-05.
• 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

The registry describes a completed, randomized, Phase 1, single-dose, two-period, two-sequence crossover study of esomeprazole 20 mg delayed-release capsules under fasted conditions in healthy adults. Enrollment was 61. The primary endpoint was Cmax, measured from scheduled blood samples and summarized using geometric means and geometric coefficients of variation. The reported primary comparison is a ratio of geometric least-squares means with a 90% confidence interval; the registry identifies it as an equivalence analysis.

The interval spans equality, but the equivalence limits and detailed statistical method are not reported in the registry record, so the equivalence decision cannot be assessed from the posted result alone. The primary pharmacokinetic analysis population consisted of participants completing both periods with relevant data; the reported Cmax counts are 44 per product. The record also lists no serious adverse events or deaths, and reports other adverse events in both product groups. Incomplete participant accounting, missing outcome results, and inconsistent masking descriptions limit further interpretation.