Relative Bioavailability of Linaprazan for the Test Formulation vs. Reference Formulation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Relative Bioavailability of Linaprazan for the Test Formulation vs. Reference Formulation (NCT05627518), a randomized phase 1 study. The primary outcome is Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratios of AUCinf and AUClast.

2. Clinical Question

The trial also lists secondary pharmacokinetic outcomes for linaprazan glurate, including comparisons of peak concentration and exposure under fed and fasting conditions. The study therefore addresses formulation and food-condition comparisons within one trial. It does not, from the record, establish a clinical treatment benefit: the stated primary question concerns relative bioavailability, not a health outcome. The posted results should be read as pharmacokinetic evidence for the studied doses, formulations, population, and conditions.

3. Trial Design

This was a randomized, open-label, single-center, single-dose, three-way crossover study in healthy volunteers. It is listed as Phase 1 and completed. The registry records 67 participants enrolled, with a start date of 2022-11-15 and a primary completion date of 2022-12-30. The sponsor is Cinclus Pharma Holding AB.

Each of the three treatment descriptions specifies a 100 mg dose of linaprazan glurate. Treatment A used four 25 mg reference tablets under fasting conditions. Treatment B used one 100 mg test tablet under fasting conditions. Treatment C used one 100 mg test tablet under fed conditions. The study was designed to compare the new test formulation with the reference formulation while fasting, and to assess the effect of a high fat, high calorie meal on pharmacokinetics after the test formulation.

In a crossover design, participants receive more than one study treatment, so comparisons can be made within the same person. This can help account for stable differences between participants. The registry identifies the study as a crossover but does not report the treatment sequences, the interval between doses, or how sequence assignment was handled. Those details are not reported in the registry record and should not be inferred.

The study was open-label, meaning masking is listed as none. The record does not describe additional safeguards for measurement or analysis. The enrollment total and the numbers listed in the adverse-event groups do not, by themselves, identify how many participants completed each treatment or contributed to each pharmacokinetic comparison. Those details 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: Approximately 84 healthy volunteers were planned to be screened to achieve 54 randomized subjects. 97 Volunteers were actually screened for eligibility, of those, 67 were Randomized and 49 Analyzed.

Only the first 6 of 8 groups are shown.

Treatment Period 1

Reasons for not completing this period:

Treatment Period 2

Reasons for not completing this period:

Treatment Period 3

Analysis population for the primary outcome, as defined in the registry: 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: 13 subjects were erroneously underdosed with 1x25 mg LG instead of 4x25 mg in the sequence arms starting with treatment A. These 13 subjects were excluded from the analysis set and replaced. Data was collected nevertheless and presented as "exploratory". This is why there is an imbalance between the number in the first two sequence arms. In addition, in error, one subject recieved the treatments in reverse order from his/her randomization. E.g. B C A instead of as randomized to A C B.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratios of AUCinf and AUClast, measured over From pre-dose up to 72 h post dose.

The primary endpoint compares linaprazan exposure after the test formulation with exposure after the reference formulation. It uses the ratios of AUCinf and AUClast for Treatments B versus A. AUC is the area under the plasma concentration–time curve: AUCinf represents exposure from time zero extrapolated to infinity, while AUClast represents exposure from time zero to the last measurement. The registry describes the measurement window as from pre-dose up to 72 h post dose.

The endpoint is reported as a geometric mean measure, with standard deviation identified as the dispersion measure. The unit is hours * nmol/Liter. A ratio-based comparison is relevant to relative bioavailability because it expresses exposure for one formulation relative to another. The endpoint description says the comparison is intended to show how much linaprazan exposure is increased or decreased with the new formulation.

As a general statistical explanation, AUC summarizes concentration over time rather than focusing on a single concentration measurement. AUCinf and AUClast use different endpoints for the integration period, so they can provide complementary summaries of exposure. The registry lists both as primary measures. Their numerical estimates, confidence intervals, and other inferential results are not reported in the registry record, so the direction and precision of the observed formulation comparison cannot be assessed from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, open-label, three-way crossover study. These design features shape how the pharmacokinetic comparisons should be understood. The primary question compares two formulations under fasting conditions, while a separate treatment condition uses the test formulation with food. The record identifies the PK Analysis Set as the population for the primary endpoint. It does not report the detailed statistical analysis plan, model specification, or numerical outcome estimates.

What does a crossover comparison mean?

General explanation: in a crossover study, participants receive multiple treatments, and each participant can contribute measurements under more than one condition. A within-participant comparison can reduce the influence of stable between-person differences, because the same person serves as a comparison for their other treatment periods. This advantage depends on appropriate conduct and analysis. Treatment order, period effects, and possible carryover from one treatment period to another can matter. The registry identifies the crossover design but does not report treatment sequences, period length, washout interval, or analyses of these effects. Their handling is therefore not reported in the registry record.

Randomization concerns assignment to treatment order or sequence in this design, but the registry does not specify how randomization was implemented or whether allocation concealment was used. Masking is listed as none, so the study was open-label. The record does not say whether laboratory measurement or data analysis was blinded. These details should not be assumed.

Why use AUC measures?

General explanation: plasma concentration changes over time after a dose. AUC summarizes the concentration profile across a time interval, rather than describing concentration at only one sampling time. AUCinf extends the summary from time zero to infinity, while AUClast ends at the last measured concentration. Here, the registry describes measurements from pre-dose up to 72 h post dose and identifies the unit as hours * nmol/Liter. AUCinf may involve extrapolation beyond the last observation as part of its definition; the record does not describe the method or amount of extrapolation used in this study.

The primary endpoint is expressed as ratios of geometric means for the test formulation relative to the reference formulation. General explanation: geometric means are often used for positive measurements that are analysed on a logarithmic scale, and ratios are a natural way to express relative exposure. This is a general description, not confirmation of the study’s analysis model. The registry lists a geometric mean parameter and standard deviation as the dispersion measure, but does not report whether the model used log-transformed values, how the ratio and its uncertainty were calculated, or what covariates were included.

How should uncertainty be read?

General explanation: an estimate summarizes the observed data, while an interval estimate such as a confidence interval conveys the uncertainty associated with that estimate under a specified method. A narrow interval indicates greater precision than a wide interval, all else being equal. A p-value, if reported, addresses compatibility of the data with a specified null model; it does not by itself quantify the size or clinical importance of a difference. The numerical estimates, confidence intervals, and p-values for the primary comparison are not reported in the registry record. No inferential conclusion about the formulation comparison can therefore be recovered from the endpoint definition alone.

The registry lists secondary outcomes for relative bioavailability of linaprazan glurate, including Cmax and fed-versus-fasting comparisons for AUCinf, AUClast, and Cmax. Cmax is the maximum measured concentration and is a peak-concentration measure; this is a general definition. The posted descriptions identify the intended comparisons but do not give their numerical results. The record lists 8 outcome measures and 12 analyses, but the full analysis plan and how multiplicity was handled are not reported in the registry record.

What does over-dispersion mean in general?

General explanation: over-dispersion occurs when observed variation is greater than expected under a model’s assumptions. It can make standard errors too small if the extra variation is ignored, and can affect interval estimates and tests. It is not reported whether over-dispersion was assessed or relevant to these pharmacokinetic analyses. No such issue should be inferred from the design description or outcome labels.

The trial record includes sample-size assumptions for planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those illustrations are not the trial’s own design justification, and the record does not report a sample-size justification for this study. They are planning examples, not observed power and not evidence that the study had a particular probability of detecting an effect. The numerical illustration outputs are not because they are not stated in the registry entries available for this explanation.

Finally, the primary analysis population is named as the PK Analysis Set, but membership rules, exclusions, and the number analysed are not reported in the registry record. Missing concentration data, handling of incomplete profiles, and sensitivity analyses are also not reported. These omissions limit independent assessment of how the planned pharmacokinetic summaries were produced.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome based on the ratios of AUCinf and AUClast for the fasting test-versus-reference comparison. It also lists secondary pharmacokinetic outcomes involving Cmax and fed-versus-fasting comparisons. The record lists 8 outcome measures and 12 analyses. The detailed statistical plan, the hierarchy among the outcomes, and any adjustment for multiple comparisons are not reported in the registry record.

Multiplicity matters in general when several outcomes or comparisons are examined: the more questions tested, the greater the chance that at least one result may appear notable by chance under a collection of null hypotheses. This general issue does not establish that any result in this study is misleading. Without the analysis plan and numerical results, it is not possible to determine what multiplicity strategy, if any, was used or how it affects interpretation. The primary designation helps identify the main stated question, but does not substitute for the missing details about inference.

The primary outcome names the PK Analysis Set, but the definition and size of that population are not reported in the registry record. The record does not describe how missing samples, incomplete concentration profiles, or participants who did not contribute to all treatment conditions were handled. It also does not report imputation methods, exclusions, or sensitivity analyses. Enrollment of 67 should not be treated as the number analysed for every outcome.

These are reporting limits, not proof that the analyses were omitted. The available record does not establish what procedures were prespecified or used. Readers should distinguish the reported design and endpoint labels from unreported details of analysis and missing-data handling.

11. 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 1.40% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: skin bacterial infection (1.9%).

The safety record lists serious adverse events by treatment group. Treatment A has 51 participants at risk and 0 serious adverse events; Treatment B has 53 at risk and 1 serious adverse event; Treatment C has 50 at risk and 0 serious adverse events. A separate group titled Reference lists 13 at risk and 0 serious adverse events. Deaths are listed as 0 in each group. The record lists Skin Bacterial Infection at 1.9% among the top serious terms.

These group counts are safety summaries, not pharmacokinetic results. The registry lists other, non-serious adverse events separately: 17 for Treatment A, 12 for Treatment B, 14 for Treatment C, and 4 for the separate Reference group. The record does not explain the relationship between that separate Reference group and the treatment groups. Because this is a crossover study, group counts should not be added or interpreted as distinct participants without further information. They also should not be taken as the number enrolled or the number in the PK Analysis Set.

General interpretation: serious adverse-event counts describe events recorded under the registry’s categories; they do not by themselves establish a causal relationship to a treatment. The record does not report event narratives, assessment of relatedness, or additional context for the listed serious term. These figures describe what is listed, not a comparative safety conclusion.

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

This trial is designed to answer a focused pharmacokinetic question: how linaprazan exposure compares after a new 100 mg tablet and a reference tablet regimen under fasting conditions, and how food affects pharmacokinetics after the new tablet. Its randomized, three-way crossover design places those conditions within one study of healthy volunteers. The primary measures are ratios of AUCinf and AUClast for linaprazan, from pre-dose up to 72 h post dose.

The registry entries do not include numerical results for those primary measures. They therefore do not establish the size or direction of the observed exposure comparison, its precision, or whether it met any prespecified criterion. The registry record does not report a decision threshold or equivalence margin. No claim of equivalence, bioequivalence, or a meaningful difference can be made from the endpoint description alone.

The study is also not a clinical-outcome trial. It evaluates pharmacokinetics and relative bioavailability in healthy volunteers after single doses. General explanation: pharmacokinetic measures describe drug concentrations and exposure; they are not, by themselves, evidence of a clinical benefit or harm in a patient population. The record does not describe outcomes in patients or repeated dosing.

The design has features that can support within-person comparisons, but important details are absent from the registry record, including treatment sequences, washout interval, analysis model, missing-data handling, and the size and rules of the PK Analysis Set. The listed safety counts provide limited descriptive information and do not establish comparative causality. These boundaries are important: the record defines the question and the intended measures, but the available numerical details do not permit a full assessment of the pharmacokinetic findings.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it combines two related but distinct questions in a crossover design. The fasting comparison evaluates a new tablet formulation against a reference formulation, while the fed condition evaluates the test tablet after a high fat, high calorie meal. Treating these as separate comparisons helps keep formulation effects distinct from food-condition effects.

The primary endpoint uses AUCinf and AUClast, two summaries of exposure over time, rather than relying on a single concentration measurement. Ratios are an intuitive way to express relative exposure between formulations. The stated endpoint therefore links the study design to the pharmacokinetic question: whether the exposure profile differs when the test tablet replaces the reference tablets under fasting conditions.

The crossover arrangement can be useful for this type of comparison because each participant may contribute under multiple conditions, allowing within-person contrasts. General explanation: this can reduce the influence of stable differences between individuals, while making period, sequence, and carryover considerations important. The registry identifies the crossover structure but does not report enough operational or analytical detail to evaluate how those considerations were handled.

The study also illustrates why an endpoint label and design description are not a complete statistical report. Interpretation depends on effect estimates and uncertainty, the analysis population, model specification, missing-data procedures, and any approach to multiple comparisons. Those details and the numerical primary pharmacokinetic results are not reported in the registry record. The posted tables and plots can be consulted for the summaries they display, but their values should be read alongside the corresponding measure and comparison.

Finally, the record includes planning illustrations based on an observed effect. Such illustrations can show how planning assumptions relate to a hypothetical future study, but they are not the study’s own design justification and are not observed power. Keeping that distinction clear is part of interpreting statistical evidence responsibly.

14. 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 gives the study’s broad design and primary endpoint but does not report numerical primary pharmacokinetic results in the registry record. Estimates, confidence intervals, and p-values are therefore unavailable for assessing the direction, magnitude, or precision of the main comparison. The record also does not state a decision threshold or equivalence margin.

Several details needed to evaluate a crossover analysis are not reported in the registry record: treatment sequences, the interval between doses, period details, and analyses of sequence, period, or carryover effects. The statistical model, transformations, covariates, and method for calculating uncertainty are also not reported. The primary analysis population is named as the PK Analysis Set, but its size and inclusion criteria are unavailable.

Missing-data procedures and sensitivity analyses are not reported. The record lists multiple outcomes and analyses but does not describe any multiplicity strategy. These omissions limit assessment of how robustly the endpoint estimates were produced and how secondary comparisons should be interpreted.

The study was open-label and conducted in healthy volunteers after single doses. The record does not report masking of laboratory measurement or analysis, and the findings described by the study question are not patient clinical outcomes. The adverse-event groups have different numbers at risk, including a separate Reference group whose relationship to the treatment groups is not explained. These safety counts cannot be used to infer the pharmacokinetic analysis population or a causal treatment effect. The enrollment total of 67 does not resolve those uncertainties.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Relative Bioavailability of Linaprazan for the Test Formulation vs. Reference Formulation — NCT05627518.
• Registry record last updated 2025-04-03; status last verified 2025-02.
• Results first posted 2025-04-03.
• 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.

18. Record Summary

NCT05627518 is a completed Phase 1, randomized, open-label, single-center, single-dose, three-way crossover study sponsored by Cinclus Pharma Holding AB. It enrolled 67 healthy volunteers. The study compared a 100 mg test tablet with a 100 mg reference regimen under fasting conditions and assessed the test tablet under fed conditions.

The primary endpoint was the ratio comparison of AUCinf and AUClast for linaprazan, using the PK Analysis Set and a measurement window from pre-dose up to 72 h post dose. Secondary outcomes included peak concentration and fed-versus-fasting pharmacokinetic comparisons. Numerical primary results and key statistical analysis details are not reported in the registry record.