A Study to Compare the Bioavailability (BA) of Dexlansoprazole Delayed-release Capsules: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Compare the Bioavailability (BA) of Dexlansoprazole Delayed-release Capsules (NCT03801148), a randomized phase 1 study. The primary outcome is Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole.

2. Clinical Question

This is a bioavailability comparison, not a trial of clinical outcomes. Its central statistical contrast concerns exposure after single doses under the study conditions: healthy volunteers, administration after a high-fat meal, and sampling from predose through multiple time points up to 24 hours after dosing. The two dose levels were handled in separate parts of the study. The 30 mg comparison is between the two manufacturers’ 30 mg capsules; the 60 mg comparison is between their 60 mg capsules.

The registry identifies the study as randomized, open-label, single-center, and crossover. In a crossover, a participant receives both treatments in a planned sequence, so the comparison can use within-participant information. Randomization determines the sequence; the record lists both possible orders within each dose part. The main question is whether the observed concentration profiles, summarized by maximum concentration, differ between the two manufacturing sources. The record does not report a clinical benefit or harm question, and the posted endpoint is pharmacokinetic rather than a patient-centered outcome.

3. Trial Design

The registry describes a Phase 1, randomized, open-label, single-center, single-dose, two-period, two-part crossover study in healthy subjects. It was sponsored by Takeda and is recorded as completed. The study started on 2019-01-10, with primary completion on 2019-02-25. Enrollment was 122.

The trial had separate dose parts. Part 1 compared 30 mg delayed-release capsules manufactured at TOB with 30 mg capsules manufactured at TPC. Part 2 made the corresponding comparison at 60 mg. Within each part, participants were assigned to one of the two treatment orders: TOB followed by TPC, or TPC followed by TOB. Each was administered orally once after a high-fat, high-calorie breakfast on Day 1 of Period 1, followed by a minimum 5 day washout before the other formulation. The registry’s descriptions of some arm regimens are truncated, so no additional schedule details can be established from the record.

Open-label means that masking was not used, as stated in the registry. That is distinct from randomization: treatment order was randomized, but participants and study personnel were not masked. The crossover structure means that the two formulations were compared within each dose part and treatment sequence, rather than as a simple parallel-group assignment in which each participant received only one formulation. The registry does not report the randomization procedure, sequence allocation details, or a period-specific analysis plan.

The primary analysis population is described as the pharmacokinetic evaluable set. Its listed requirements include enrollment, receipt of at least one dose, not being discontinued and replaced, completion of pharmacokinetic sampling in both periods, and sufficient protocol compliance. The full eligibility wording is not reported in the registry record. The registry reports 60 participants in each 30 mg arm and 57 in each 60 mg arm for the primary endpoint summaries; the adverse-event populations are described separately. Those arm-level analysis counts should not be treated as the overall enrollment count.

The record reports four outcome measures and eight analyses, but only the primary endpoint information is described in the posted results included in this record. The sample-size justification, planned statistical analysis details, and rules for handling sequence, period, or carryover effects 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 participants were enrolled in this 2-part and 2-way crossover study to receive dexlansoprazole 30 milligram (mg) capsules manufactured by Takeda GmbH Plant Oranienburg (TOB) and 30 mg capsules manufactured by Takeda Pharmaceutical Company Ltd. (TPC) in Part 1 and dexlansoprazole 60 mg capsules by TOB and 60 mg capsules by TPC in Part 2.

Period 1 (2 Days)

Reasons for not completing this period:

Washout Period (at Least 5 Days)

Reasons for not completing this period:

Period 2 (2 Days)

Follow-Up (12 Days)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic (PK) evaluable set included all participants who enrolled into study and received at least one dose of study drug, were not discontinued from study and replaced with other participants, who completed PK sampling in both periods, complied sufficiently with protocol, and displayed evaluable PK profiles.

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: The safety set included all participants who enrolled into the study and received at least one dose of the study drug(s).

6. Primary Endpoint

The registry lists the primary outcome as Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole, measured over Day 1 pre-dose and at multiple time points (up to 24 hours) post dose.

The primary endpoint is Cmax, the maximum observed plasma concentration of dexlansoprazole, measured in nanograms per milliliter. It summarizes the highest measured concentration in the pharmacokinetic sampling profile after dosing. The registry specifies predose sampling and multiple post-dose time points up to 24 hours.

In general, Cmax is used in bioavailability comparisons because it captures the peak concentration observed after a dose. It is one aspect of drug exposure; it does not by itself describe the entire concentration-time profile or total exposure. Other pharmacokinetic measures can address different features, but the record’s primary endpoint is specifically maximum observed concentration.

The endpoint summaries are geometric means, with geometric coefficient of variation as the dispersion measure. In general, geometric summaries are useful when measurements are positive and vary multiplicatively or are right-skewed. A geometric coefficient of variation describes relative variability on a multiplicative scale; it is not a confidence interval and should not be read as a range containing a specified proportion of individual observations.

The registry reports the Cmax outcome separately for the 30 mg and 60 mg parts, and gives a geometric least-squares mean ratio with a 90% confidence interval for each comparison. The confidence intervals describe uncertainty around the estimated relative comparison under the analysis used. The registry does not report the endpoint’s equivalence margin or the detailed model used to obtain the least-squares means, so the clinical or regulatory decision rule cannot be reconstructed from these results alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover comparison contribute?

In general, a crossover design gives each participant more than one treatment, in a randomized order. When the outcome is measured in each period, the comparison can account for some stable differences between participants because each person contributes information under both treatments. This may improve precision compared with a parallel design, but only if the analysis and conduct appropriately address the paired structure, treatment sequence, and period.

Here, the registry describes two periods within each dose part and lists both formulation orders. It also specifies a minimum 5 day washout. A washout is intended to separate treatment periods, but its presence alone does not establish that all carryover concerns were eliminated. The registry does not report the washout’s justification, an assessment of carryover, or how period and sequence were handled statistically. Those details are not reported in the registry record.

What does the ratio represent?

In general, a geometric least-squares mean ratio compares estimated geometric means on a relative scale. A ratio of 1 represents equal estimated values on that scale. A ratio below 1 means the numerator estimate is lower than the denominator estimate; a ratio above 1 means it is higher. The registry presents ratios for TOB relative to TPC in the 30 mg and 60 mg comparisons. These are not raw differences in ng/mL.

Least-squares means are model-based estimates. They may account for features of the analysis model, while the displayed arm geometric means are summaries of the observed endpoint values. The registry does not identify the model, its covariates, transformation details, or its treatment of the crossover structure. Therefore, the ratio cannot be independently reproduced from the record’s arm summaries alone. A simple division of the posted geometric means would not necessarily reproduce the reported model-based ratio.

How should a confidence interval be read?

In general, a confidence interval expresses the precision of an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval on the same scale. A 90% confidence interval is not a statement that there is a 90% probability that the particular fixed interval contains the true value. Rather, the confidence level describes the long-run performance of the interval procedure under its assumptions.

For a ratio, the value 1 is the reference point for equal relative estimates. The 30 mg interval includes 1; the 60 mg interval is entirely above 1. This helps describe how the interval relates to equality, but it is not by itself a test of equivalence. Equivalence requires a prespecified range of acceptable ratios, and the registry does not report that range. The confidence level and the equivalence bounds together determine how an equivalence conclusion is assessed.

Why are geometric summaries used?

In general, pharmacokinetic measurements are positive and can have multiplicative variability. A geometric mean summarizes the central value on a logarithmic scale and then expresses it in the original measurement units. The geometric coefficient of variation expresses relative dispersion rather than absolute spread in ng/mL. It should not be interpreted as the standard deviation, nor as the interval for the estimated ratio.

The posted Cmax geometric means and coefficients of variation are descriptive. They provide context for the distributions and variation in each arm, but they do not alone quantify the uncertainty in the within-participant treatment contrast. The ratio and its confidence interval address that comparative question more directly.

What can be concluded about the analysis method?

The registry classifies the reported comparisons as equivalence analyses and gives geometric least-squares mean ratios with 90% confidence intervals. The method field is not reported, and the record does not provide the model specification, the equivalence margin, a p-value, or detailed handling of missing pharmacokinetic samples. It is therefore not possible to verify the exact inferential procedure or reproduce its estimate from the posted summaries.

In general, an equivalence analysis asks whether the uncertainty around a treatment comparison is contained within prespecified limits regarded as practically acceptable. It is not enough that a conventional test fails to find a difference. The margin must be chosen before examining the results and justified for the context. Because the margin and justification are not reported in the registry record, the posted label should be read as the registry’s analysis classification, not as a complete record of the decision rule.

What do the planning illustrations mean?

In general, sample-size planning illustrations based on an observed effect explore how a hypothetical future design might perform under chosen assumptions. They are not the observed power of a completed study, and they do not establish that the original trial was planned using the same assumptions. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The registry does not report the trial’s own sample-size justification, so the illustrations cannot be treated as the original design rationale.

Planning based on an observed effect has an additional limitation: the observed estimate is uncertain and can be an unstable basis for projecting a future study. In general, design decisions should also consider the target effect, variability, analysis method, and an appropriate margin or clinically meaningful threshold. The available registry record does not report those planning choices for this trial.

10. Analyses Reported by the Sponsor

The registry’s reported comparisons are geometric least-squares mean ratios with 90% confidence intervals, classified as equivalence analyses. These are the sponsor-reported results available in the record. The registry does not provide the detailed statistical method or model needed to reconstruct those adjusted comparisons from the arm-level geometric means and coefficients of variation.

No separately identified recalculated ratios or confidence intervals are reported in the registry record. The arm summaries are descriptive, while the sponsor’s ratios are model-based estimates; they are not interchangeable. Because the record does not identify the model or provide individual-level data, a direct independent reproduction of the sponsor’s analysis is not possible from the posted summaries alone.

The record does not indicate a discrepancy between a recalculation and the sponsor’s analysis. The most useful interpretation is therefore to report the sponsor’s estimates and intervals as posted, while noting that the equivalence margin and analysis details are unavailable. For the 30 mg comparison, the interval includes 1; for the 60 mg comparison, the interval is above 1. Whether either result satisfies the intended equivalence criterion cannot be established without the criterion and full statistical plan.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and eight analyses, while the available primary results describe Cmax comparisons for the two dose parts. The number of secondary outcomes with posted results is 0. The record does not explain how the full set of outcomes or analyses was organized, or whether any multiplicity adjustment was planned or used.

In general, multiplicity arises when several outcomes, doses, comparisons, or analyses are examined. The more inferential questions considered, the greater the chance that some estimates will appear noteworthy by chance if each is interpreted independently. A prespecified testing hierarchy or adjustment can address this issue, but the registry does not report whether such an approach was planned for these analyses. The two dose comparisons are presented separately, and no combined or adjusted conclusion should be inferred from that presentation.

The primary analysis population is described as pharmacokinetically evaluable. It included participants who enrolled and received at least one dose, were not discontinued and replaced, completed pharmacokinetic sampling in both periods, and complied sufficiently with the protocol. The registry description ends before its full criteria are specified. The number excluded from this set, reasons for exclusion, and any sensitivity analyses are not reported in the registry record.

Missingness matters in a crossover study because a participant may have endpoint data in one period but not the other. In general, incomplete paired data can reduce information and can affect the comparison if missingness relates to treatment or outcome. The registry does not report the amount, timing, or reasons for missing pharmacokinetic samples, nor how incomplete period data were handled. It also does not report imputation procedures or sensitivity analyses for missing data.

The record does not report interim analyses, stopping rules, or a detailed statistical analysis plan. The absence of those details from the registry record does not establish that no such procedures existed; it means their presence and implementation cannot be assessed from the posted information.

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 adverse-event summaries list no serious adverse events in any of the four dose-and-manufacturer groups. The numbers at risk were 61 for each 30 mg group and 59 for each 60 mg group; the number affected by a serious adverse event was 0 in each group. Deaths were also 0 in each group. The registry lists no top serious adverse-event terms.

The record separately reports other, non-serious adverse events: 4 affected participants in the 30 mg TOB group, 3 in the 30 mg TPC group, 7 in the 60 mg TOB group, and 5 in the 60 mg TPC group. These are counts, not rates adjusted for exposure or duration. The study was a single-dose Phase 1 study in healthy volunteers, and the registry’s safety summary does not provide event descriptions or a detailed assessment of severity, timing, or relationship to treatment.

In general, zero observed serious events in these groups does not prove that the risk is zero. A safety count describes what was observed in the recorded study population and does not rule out uncommon events or characterize longer-term use. The safety figures should be read separately from the primary pharmacokinetic comparisons; they do not determine whether the Cmax comparisons met an equivalence criterion.

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

The posted results describe the maximum observed plasma concentrations after single doses of two manufacturing-source formulations, separately at 30 mg and 60 mg, under high-fat-meal conditions. For 30 mg, the reported ratio is close to 1 and the 90% confidence interval includes 1. For 60 mg, the reported ratio is above 1 and the confidence interval lies above 1. These findings describe relative Cmax estimates and their statistical uncertainty; they are not clinical outcome results.

The registry labels the analyses as equivalence comparisons, but it does not report the equivalence margin or full statistical method. Consequently, the posted results alone cannot establish whether the prespecified equivalence criterion was met. A confidence interval that includes 1 is not by itself proof of equivalence, and an interval entirely above 1 does not, without the margins, settle an equivalence decision. The exact decision rule is not reported in the registry record.

These results do not show whether either formulation improves or worsens symptoms, prevents disease, or changes any other clinical outcome. Cmax is a pharmacokinetic measure, and no clinical effectiveness endpoint is described in the posted primary results. Nor do the findings establish long-term safety: the study involved single-dose administration and reports only the adverse-event summaries available in the registry.

Generalizability is also limited by the study population and conditions. The participants were healthy volunteers, and dosing followed a high-fat meal. The results do not directly describe other populations, dosing schedules, meal conditions, or repeated use. The record does not report evidence on those settings.

Overall, the record supports a narrow interpretation: it provides dose-specific relative Cmax estimates and confidence intervals for the two manufacturing sources, along with descriptive variability and adverse-event counts. It does not provide enough detail to independently verify the full equivalence procedure or extend the findings to clinical outcomes.

14. Why This Trial Matters Statistically

This trial illustrates why the design and estimand matter when reading a bioavailability comparison. The crossover design compares two formulations within randomized treatment sequences, while the reported endpoint is a concentration measure rather than a clinical outcome. Reading the result as a simple comparison of two unrelated groups would miss the paired structure described in the registry.

It also shows why descriptive summaries and inferential estimates should be kept distinct. The geometric means summarize observed Cmax values in each group. The geometric least-squares mean ratios and confidence intervals represent the reported comparative analysis. Without the model details, the latter cannot be rebuilt from the arm summaries alone. A statistical report is most interpretable when it gives both the estimate and enough information about how it was obtained.

Equivalence questions depend on more than whether an interval contains the equality value. The equivalence margin defines how far apart the formulations may be while still meeting the intended criterion. Since the registry does not report that margin, the analysis label and interval cannot independently establish the decision. This is a useful distinction between estimating a relative difference and demonstrating equivalence under a prespecified rule.

The record also highlights the importance of population definitions and missing-data reporting. The primary analysis used a pharmacokinetically evaluable set with requirements related to dosing, sampling in both periods, replacement, and protocol compliance. The registry does not fully describe exclusions or missing measurements. Those details affect how readers understand which observations contribute to the estimate.

Finally, the study’s scope is specific: healthy volunteers, single-dose administration, and dosing after a high-fat meal. Statistical interpretation should remain aligned with that setting and the endpoint actually measured. The posted results are informative about the stated pharmacokinetic comparison, not a substitute for clinical outcomes or longer-term safety 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.

The registry record does not report the equivalence margin, the statistical model, or the detailed analysis plan. Without these, readers cannot verify how the geometric least-squares mean ratios were estimated, determine the exact decision rule, or independently reproduce the sponsor’s analysis from the posted arm summaries. No p-values are reported.

The primary analysis population is described as pharmacokinetically evaluable, but the description is incomplete. The record does not report how many participants were excluded from that population, why participants may have been discontinued or replaced, or how missing pharmacokinetic samples were handled. It also does not report sensitivity analyses addressing exclusions or missing data.

The registry describes randomized treatment sequences but does not report the randomization method or how sequence and period effects were handled. It specifies a minimum 5 day washout, but does not report the rationale for that interval or an analysis of carryover. These omissions limit assessment of the crossover analysis.

The trial was open-label and single-center, and enrolled healthy volunteers. Its primary endpoint was Cmax after a single dose following a high-fat meal. Those features restrict interpretation to the conditions and population recorded; the results do not directly address other populations, repeated dosing, other meal conditions, or clinical outcomes. The registry does not report a sample-size justification, so the adequacy of enrollment for the intended equivalence assessment cannot be judged from the record.

The safety information is also limited to summary counts. Serious-event counts were zero in the listed groups, but the record does not provide a detailed account of event timing, duration, severity, or relatedness. These limitations do not negate the posted results, but they define what can be concluded from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Compare the Bioavailability (BA) of Dexlansoprazole Delayed-release Capsules — NCT03801148.
• Registry record last updated 2020-03-19; status last verified 2020-03.
• Results first posted 2020-03-19.
• 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

NCT03801148 is a completed Phase 1, randomized, open-label, single-center, single-dose, two-period, two-part crossover study sponsored by Takeda. It enrolled 122 healthy volunteers and compared dexlansoprazole delayed-release capsules manufactured at TOB and TPC at 30 mg and 60 mg, after a high-fat meal.

The primary endpoint was maximum observed plasma concentration, summarized with geometric means and geometric coefficients of variation. The registry reports geometric least-squares mean ratios and 90% confidence intervals for the two dose comparisons, classifying them as equivalence analyses. The equivalence margin and detailed statistical method are not reported in the registry record.

The adverse-event summaries report no serious adverse events or deaths in the listed groups. The posted record supports interpretation of dose-specific Cmax comparisons under the study conditions, but not conclusions about clinical outcomes or settings beyond those studied.