Pharmacokinetics of Immediate-Release vs. Delayed-Release Omeprazole in Gastroparesis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics of Immediate-Release vs. Delayed-Release Omeprazole in Gastroparesis (NCT00492622), a randomized phase 4 study. The primary outcome is Time to Maximal Omeprazole Concentration (Tmax).

2. Clinical Question

3. Trial Design

The registry describes a Phase 4 randomized, unmasked crossover study sponsored by the University of Louisville. It lists enrollment as 12 and the study status as completed. The recorded start was 2007-06, and primary completion was 2008-12. The population of interest was patients with heartburn associated with gastroparesis; the listed conditions are gastroparesis and gastroesophageal reflux disease.

The crossover structure means participants received both formulations in a sequence rather than remaining in a single formulation group throughout. One sequence began with immediate-release omeprazole for 7 days and then changed to delayed-release omeprazole for 7 days. The other began with delayed-release omeprazole for 7 days and then changed to immediate-release omeprazole for 7 days. The registry identifies the sequence groups, but the reported primary outcome population includes all subjects regardless of which formulation they received first.

Masking is listed as none. That means the registry does not describe the study as blinded. Random allocation is recorded, but the allocation procedure and the method used to preserve allocation concealment are not reported in the registry record. A washout period between treatment periods, if any, is not reported in the registry record. The registry also does not report the detailed recruitment procedures or eligibility criteria.

This design can support within-participant comparisons because each participant received both formulations. Such a comparison accounts for stable differences between participants, but interpretation can also depend on the treatment sequence and on effects that persist from one period into the next. How sequence, period, or carryover effects were assessed is not reported in the registry record. The reported formulation-level results are means and standard deviations, while the inferential analysis is identified as paired t-tests.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All subjects were included regardless of which formulation they received first.

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 Time to Maximal Omeprazole Concentration (Tmax), measured over 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 and 300 min after the study drug was ingested on day 7 of treatment.

The primary endpoint is time to maximal omeprazole concentration, abbreviated Tmax and measured in minutes. It describes how long after ingestion it takes for the measured omeprazole concentration in blood to reach its maximum. It is a pharmacokinetic measure: it describes the timing of drug concentration, rather than directly measuring symptom relief, disease control, or overall amount of drug absorbed.

The registry specifies blood measurements at 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 and 300 minutes after the study drug was ingested on day 7 of treatment. A difference in Tmax can therefore indicate a difference in the timing of peak concentration. It does not, by itself, establish a difference in total exposure. Other concentration-based measures would be needed to characterize that aspect of pharmacokinetics; a reported endpoint for total exposure is not included in the primary outcome information.

The registry reports the endpoint as a mean with standard deviation for each formulation and reports a paired t-test analysis. A mean describes the average Tmax in the measured group, while the standard deviation describes variation among the observed values. Neither statistic alone reveals the full distribution or the precision of the within-participant contrast. A confidence interval for the paired contrast is not reported in the registry record.

In this setting, Tmax is useful for comparing the timing of peak concentrations under the two formulations. It answers a narrower question than whether one formulation is better absorbed overall: the primary endpoint is time to the peak, not the peak concentration itself or an integrated measure of blood drug levels.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The reported inferential method is a paired t-test. In general, a paired test analyzes the within-person difference between two measurements, rather than treating the measurements as if they came from unrelated groups. That is a natural form of comparison for a crossover design in which each participant received both formulations. It can account for stable participant characteristics because each person serves as their own comparison. The method still relies on assumptions about the paired differences, including that their distribution is adequately represented by the test’s model. The registry does not report diagnostic checks or alternative analyses.

What do the means and standard deviations describe?

The mean is the arithmetic average of the observed Tmax values for a formulation. The registry reports 32.0 minutes for immediate-release omeprazole and 97.0 minutes for delayed-release omeprazole. The standard deviation describes the spread of individual values around their formulation mean; the reported standard deviations are 11.0 and 46.0, respectively. A larger standard deviation indicates more dispersion in the observed values, but does not by itself explain why the values vary.

These summaries are not the same as a paired treatment effect. To understand the paired comparison, the relevant quantity is each participant’s difference between formulations and the average of those differences. The registry does not report that paired estimate, its standard deviation, or a confidence interval. The two separate standard deviations cannot be used to recover the paired uncertainty without information about the relationship between each participant’s measurements. No such calculation is made.

How should the p-value be read?

A p-value describes how compatible the observed test result is with a specified null model, assuming that model and the test assumptions hold. The registry reports p < 0.01 for paired t-tests. This communicates a threshold rather than an exact p-value. It does not measure the probability that the result is due to chance, the probability that the null is true, or the size of the effect. The record does not provide a confidence interval for the paired contrast, which would help show the range of values compatible with the analysis.

The registry marks the analysis type as equivalence. In general, an equivalence analysis asks whether the difference is sufficiently small to fall within a prespecified acceptable range. That requires a margin defined before interpreting the results, along with an estimate and uncertainty evaluated against that margin. A conventional test for a difference and an equivalence assessment answer different questions. Because the margin, estimate, and confidence interval are not reported in the registry record, the equivalence label and p-value cannot be reconciled from the posted details alone.

What does crossover structure contribute?

In a crossover study, within-participant comparison can reduce the influence of characteristics that remain relatively stable over the study periods. The recorded sequences alternate which formulation is given first. Randomization of sequence can help balance order, but the registry does not describe the randomization procedure or how sequence effects were analyzed. Period effects can arise when measurements differ over time, and carryover can arise when effects from an earlier treatment persist into a later period. Whether these possibilities were assessed, and whether a washout was used, is not reported in the registry record. The posted paired-test description does not say whether the analysis adjusted for sequence or period.

What do planning calculations mean?

General sample-size illustrations are planning scenarios, not measurements of the trial’s achieved power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. These assumptions describe hypothetical future planning, not the protocol used for this study. They do not establish that the study was designed to detect a particular effect, and they should not be read as observed power. The registry does not report the original sample-size justification or its design assumptions.

For a crossover comparison, planning should reflect the paired outcome and its variability, as well as anticipated missing measurements and the intended analysis. The planning assumptions described in the record do not provide those study-specific details. No numerical planning result should be interpreted as a count of participants actually enrolled or as a measure of the strength of evidence in the completed study.

What can be inferred from the analysis description?

The method label identifies a paired t-test, but the record does not provide enough detail to reproduce the sponsor’s test. In particular, it does not report the paired differences, the exact test statistic, degrees of freedom, or a confidence interval. It also does not explain how the analysis handled any missing measurements. These omissions limit independent assessment of precision and robustness. The descriptive means and standard deviations remain interpretable as summaries, but they do not substitute for the paired effect estimate required to fully understand the primary comparison.

10. Analyses Reported by the Sponsor

The registry’s reported analysis is the sponsor-side inferential result available for the primary comparison: paired t-tests with p < 0.01, labeled as an equivalence analysis. The posted formulation-specific means and standard deviations provide descriptive summaries, but the record does not report a paired mean difference or a confidence interval that would allow a direct comparison with the paired analysis.

No discrepancy is flagged between the reported result and a recalculated result. That does not add information beyond the registry’s stated analysis: the paired estimate, its uncertainty, and the equivalence margin remain unreported. If a simple reconstruction from summary statistics differs from the sponsor’s analysis, the sponsor’s own analysis takes precedence, because the summaries do not contain the participant-level pairing needed to reproduce a paired test. In this record, there is no reported reconstruction that supplies the missing paired estimate.

The equivalence label should not be treated as proof of equivalence without the margin and corresponding uncertainty assessment. The reported p-value indicates the result of the listed test, but the record does not specify the tested null in sufficient detail to establish how it supports an equivalence conclusion. The sponsor result is therefore best read alongside its descriptive means, with the limits of the reported analysis kept explicit.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, while the primary outcome is time to maximal omeprazole concentration. No secondary outcomes are posted in the record summarized for this analysis. The registry does not report whether the analyses were prespecified in a statistical analysis plan, how outcome priority was established beyond identifying the primary outcome, or whether any adjustment for multiple testing was applied. The presence of multiple outcomes or analyses can increase the chance of at least one apparently notable result when each is tested separately; whether that concern applies to the reported analyses depends on their prespecification and interpretation, details that are not reported in the registry record.

Missing-data handling is not described. The primary outcome population is stated to include all subjects regardless of which formulation they received first. That tells readers how the registry describes the population in relation to sequence, but it does not say whether every participant had complete measurements for both formulations or all scheduled sampling times. The record does not report how incomplete concentration measurements, missed visits, or unusable values were handled, or whether any imputation was used.

The analysis population is also not fully characterized beyond the statement that all subjects were included regardless of which formulation came first. The record does not specify whether the analysis followed randomized sequence assignment, required completed treatment periods, or used another inclusion rule. It does not report exclusions or protocol deviations. Consequently, the relationship between enrollment, the outcome summaries, and the paired-test population cannot be assessed in detail.

These reporting gaps matter particularly for a crossover analysis, where paired observations are needed to estimate within-participant differences. If one member of a pair is missing, that participant may not contribute to a conventional paired analysis, depending on the analysis method. Whether this occurred or influenced the result is not reported in 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.

The registry lists serious adverse events as 0 in the immediate-release group and 0 in the delayed-release group. It also lists deaths as 0 in both groups. The group descriptions identify 12 participants at risk in each formulation group for serious adverse events and other adverse events. The registry records 0 other adverse events in each group as well. No serious adverse event terms are listed.

These are the counts posted in the registry, not evidence that an event was impossible or that the formulations have identical safety profiles. A zero count means that no events of the listed category were recorded in the reported group during the period represented by the registry entry. The record does not provide detailed adverse-event definitions, ascertainment procedures, severity grading, or an explanation of how events were attributed across the crossover periods.

The safety counts should also be interpreted in the context of the study’s small enrollment and limited reported information. They do not establish the frequency of uncommon events or support a broad comparison of safety. The registry group title for the immediate-release serious-adverse-event entry contains a different drug-name spelling, but the intervention and other arm information identify the formulation comparison as immediate-release and delayed-release omeprazole.

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

The posted primary results describe the timing of maximal omeprazole concentration under two formulations in patients with gastroparesis. The mean Tmax was 32.0 minutes for immediate-release omeprazole and 97.0 minutes for delayed-release omeprazole. The reported standard deviations were 11.0 and 46.0. The paired analysis is reported with p < 0.01. Taken together, these results describe an earlier mean time to peak for the immediate-release formulation in the measured study population, alongside greater spread in the delayed-release values.

The result does not establish how much total omeprazole was absorbed. Tmax is about timing, not total exposure, and the posted primary outcome is not a direct measure of symptom change. The registry summary describes an interest in blood drug levels and absorption, but the primary result addresses time to maximal concentration. It does not demonstrate a clinical benefit or establish that either formulation is preferable for an individual patient.

The p-value does not quantify the magnitude or precision of the paired difference. The paired estimate and its confidence interval are not reported in the registry record. The equivalence label also cannot be evaluated without a stated margin and uncertainty assessment. Therefore, the result should not be interpreted as demonstrating equivalence, despite that label.

General interpretation of pharmacokinetic outcomes also depends on how measurements were obtained and analyzed. The registry identifies sampling times and day of treatment but does not report assay details, missing-measurement handling, or analyses of sequence and period effects. Those omissions limit assessment of how robustly the primary comparison reflects formulation differences.

Overall, the record supports a descriptive and test-based statement about Tmax in this crossover study. It does not support claims about overall absorption, effectiveness for heartburn, other clinical outcomes, or uncommon safety events. The scope of the result is the reported pharmacokinetic endpoint and the participants included in the analysis as described by the registry.

14. Why This Trial Matters Statistically

This study illustrates why endpoint choice matters in pharmacokinetic comparisons. Time to maximal concentration addresses when a peak occurs. It is distinct from peak concentration and from total exposure. A study can report a difference in timing without answering whether the total amount of drug reaching the circulation differs. Keeping these measures separate prevents a narrow timing result from being described as a broad conclusion about absorption.

The crossover design also highlights the importance of matching the statistical analysis to the way observations are collected. Because participants received both formulations, a paired analysis can use within-participant comparisons. The means and standard deviations for each formulation do not show the variability of those paired differences. Reporting the paired estimate and its confidence interval would make the size and precision of the main comparison more transparent.

The equivalence label alongside a p-value draws attention to the distinction between testing for a difference and assessing whether differences are small enough to be considered equivalent. Equivalence depends on a justified margin and an uncertainty interval evaluated against it. A label alone does not communicate that evidence. Clear reporting of the analysis objective, margin, estimate, and interval is important for readers to understand what conclusion the analysis can support.

Finally, a small completed study can be informative about a focused pharmacokinetic question while leaving important issues unresolved. Sequence and period considerations, missing-data procedures, and multiplicity handling affect interpretation, yet are not described in the registry record. The statistical lesson is not that a result should be discarded, but that its meaning depends on the estimand, paired analysis, and reporting detail available.

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 provides limited information for evaluating the primary paired comparison. It reports formulation-specific means and standard deviations and a p-value, but not the paired estimate, confidence interval, test statistic, or details needed to reproduce the analysis. The analysis is labeled as equivalence, yet an equivalence margin and the uncertainty assessment against that margin are not reported. This prevents a clear evaluation of the equivalence interpretation.

Although the design is crossover, the record does not report whether a washout period was used or how period, sequence, or carryover effects were considered. These are design-specific issues because each participant received both formulations in sequence. The registry’s statement that all subjects were included regardless of which formulation they received first does not explain how treatment order entered the analysis.

Other limitations include the absence of reported missing-data procedures, participant-level paired results, and detailed information about measurement methods. The registry does not describe the statistical analysis plan, sample-size justification, or multiplicity adjustment. Although three outcome measures and three analyses are listed, secondary results are not posted in the record summarized for this analysis. It is therefore not possible to assess how the primary result relates to the full set of planned outcomes or analyses.

The study is unmasked, and the registry does not report additional safeguards or procedures that might affect outcome assessment. The result concerns Tmax, a pharmacokinetic timing measure, rather than a direct clinical outcome or a complete measure of exposure. The posted safety counts also provide limited information about rare events. These points restrict the conclusions to the reported endpoint and analysis; they do not, on their own, invalidate the observed summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetics of Immediate-Release vs. Delayed-Release Omeprazole in Gastroparesis — NCT00492622.
• Registry record last updated 2017-07-28; status last verified 2017-06.
• Results first posted 2017-07-28.
• 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, randomized, unmasked Phase 4 crossover study compared immediate-release omeprazole 40 mg powder with delayed-release omeprazole 40 mg capsule in patients with heartburn associated with gastroparesis. The registry lists enrollment of 12 and identifies the University of Louisville as sponsor. Participants received both formulations in one of two sequences, with each treatment period described as 7 days.

The primary endpoint was time to maximal omeprazole concentration on day 7, measured in minutes after ingestion. The registry reports means and standard deviations of 32.0 and 11.0 for immediate-release omeprazole, and 97.0 and 46.0 for delayed-release omeprazole. It reports paired t-tests with p < 0.01 and labels the analysis as equivalence. A paired estimate, confidence interval, and equivalence margin are not reported.

The record lists 0 serious adverse events, 0 other adverse events, and 0 deaths in each formulation group. Interpretation is limited by unreported details about the paired effect, missing data, multiplicity, and crossover-period considerations.