Investigate Linaprazan Glurate/Linaprazan in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigate Linaprazan Glurate/Linaprazan in Healthy Subjects (NCT05742984), a randomized phase 1 study. The primary outcome is AUC0-24h Linaprazan (QD).

2. Clinical Question

This is a pharmacokinetic question: it concerns measured drug concentration over time, rather than a clinical outcome in people with GERD. Although GERD is listed under conditions, the study population is described as healthy subjects. The broader study objectives also include pharmacodynamics assessed by continuous intragastric pH measurement, as well as safety and tolerability. The registry record does not report numerical results for those objectives in the registry record for this analysis.

3. Trial Design

The registry describes a Phase 1, randomized, open-label, parallel-group study at a single center. The listed enrollment is 75, and the study status is completed. The start date is 2023-01-26 and the primary completion date is 2023-03-24. No masking is reported; the design is explicitly open label.

Interventions cover linaprazan glurate at 25 mg, 50 mg and 75 mg, with once-daily and twice-daily schedules. The arm descriptions specify administration for 14 days. The brief summary additionally describes single dosing and an additional single dose after a drug holiday of 2, 4 or 6 days. The registry entries do not link each drug-holiday duration to a particular dose group, so that mapping is not reported in the registry record.

The stated aims are pharmacokinetics, pharmacodynamics measured by continuous intragastric pH, safety and tolerability. The primary outcome is the mean AUC0-24h for linaprazan in the QD groups, measured on Day 1 and Day 14. The registry also lists 9 outcome measures, but the numerical primary outcome results and the results for the other outcomes are not reported in the registry record.

Random allocation across parallel groups can support comparisons among the assigned regimens, but the design alone does not establish that a particular comparison was planned or that a difference was found. The record does not report the randomization procedure, allocation concealment, sample-size justification, or a detailed statistical analysis plan. Those design details should not be inferred from the study being randomized or from the listed 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Overall # of participants analyzed does not match the participant flow figures due a discrepancy between "completers" and "evaluable" participants (protocol deviations). Figures here represent the number of evaluable subjects. NB! One participant in 50mg QD discontinued before completion of the full study, but only after the primary variables had been collected. Thus this participant's data was evaluable despite being a non-completer.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as AUC0-24h Linaprazan (QD), measured over Day 1 and Day 14.

The primary endpoint is titled AUC0-24h Linaprazan (QD). AUC is the area under a concentration-time curve: in general, it combines concentration measurements across a specified time interval into a measure of overall drug exposure. Here, the stated interval is 0 to 24 hours after dosing, and the stated unit is nmol/L*h. Results are specified for Day 1 and Day 14, in the once-daily groups only.

The registry identifies the endpoint summary as a mean with standard deviation. In general, the mean describes the group’s average measured exposure, while the standard deviation describes how spread out individual measurements are around that average. A mean alone does not show the range of individual values, and a standard deviation is not a confidence interval for the mean.

Pharmacokinetic exposure measures are used to characterize how much drug is present in the body over a defined interval. They are distinct from pharmacodynamic measures, such as the continuous intragastric pH monitoring also named among this study’s objectives. The primary endpoint title does not itself provide evidence about pH, safety, tolerability, or clinical benefit.

The record names the endpoint and its measurement schedule, but it does not report the mean, standard deviation, or number analyzed for either assessment. Therefore, the size and precision of the observed exposure cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the AUC measure?

In general, area under the concentration-time curve (AUC) summarizes measured concentrations across a defined period. It is not the same as a single concentration measurement: concentrations at different times contribute to the overall area. The endpoint in this study is specified from 0 to 24 hours after dosing and uses the unit nmol/L*h. The registry names two assessment days, Day 1 and Day 14, and restricts the primary endpoint to the QD groups.

AUC is a pharmacokinetic measure. It describes drug exposure over the specified interval, not a clinical outcome or a direct measure of intragastric pH. The study’s separate pharmacodynamic objective is continuous intragastric pH measurement. In general, pharmacokinetic and pharmacodynamic measures answer related but distinct questions: one concerns drug concentration over time, while the other concerns a measured physiological response.

How should the mean and standard deviation be read?

The registry specifies that the primary endpoint is summarized by a mean and standard deviation. In general, the mean is the arithmetic average of the measured values in the analysis population. The standard deviation describes variability among individual measurements around that average. It does not, by itself, show the precision of the estimated mean. A confidence interval is a separate summary used to express statistical uncertainty around an estimate, and no confidence interval for the primary endpoint is reported in the registry record.

Both the mean and its variability are useful for understanding a continuous outcome. The mean conveys the central level of observed exposure, while the standard deviation indicates how heterogeneous the measurements are within the group. Neither statistic can be interpreted numerically because the registry record does not report the endpoint values.

What can randomization establish?

In general, random allocation aims to make assigned groups comparable with respect to factors that could influence an outcome. A parallel-group design assigns participants to a regimen and compares outcomes across groups. These design features can support interpretation of between-group differences when allocation and analysis are appropriately conducted and when results are reported.

Randomization alone does not guarantee that groups were balanced in a particular realized study, nor does it reveal the size or uncertainty of an effect. The record describes the study as randomized, but the randomization method and allocation concealment are not reported in the registry record. No numerical primary-outcome comparison is reported either. Thus, the design classification should not be mistaken for evidence of a specific exposure difference.

Why does analysis population matter?

The primary outcome description distinguishes evaluable subjects from completers and attributes a discrepancy with participant-flow figures to protocol deviations. In general, the population used in an endpoint analysis determines which observations contribute to its summary. A complete-case or evaluable analysis may differ from a population defined by randomized assignment, especially when data are missing or protocol deviations occur. The exact analysis population definition and the count analyzed are not reported in the registry record.

The record also mentions a participant in the 50 mg QD group who discontinued before completion of the ful—an incomplete description. It does not report whether that participant contributed any primary endpoint measurements, how missing measurements were handled, or whether the analysis used imputation. Those details cannot be reconstructed from the available wording.

What does uncertainty require?

In general, statistical uncertainty depends on both the observed data and the analysis method. A confidence interval would give a range of values compatible with the data and model, while a hypothesis test would evaluate a specified null hypothesis under stated assumptions. The registry does not report primary endpoint estimates, confidence intervals, test statistics, or p-values. Without these, neither statistical precision nor evidence against a particular null value can be assessed.

Variability can also affect precision. When measurements are highly dispersed, the group mean may be less precisely estimated than when measurements are more tightly clustered, all else equal. This general principle does not establish the degree of variability or precision in this study; the necessary numerical outcome information is not reported in the registry record.

What about repeated measures and multiple outcomes?

The primary measure is listed for Day 1 and Day 14, and the wider study includes pharmacokinetic and pharmacodynamic objectives. In general, analysis of measurements at multiple times can require a prespecified approach to within-person correlation and to the comparisons of interest. When a study evaluates multiple outcomes or contrasts, a multiplicity strategy may be needed to manage the increased chance of false-positive findings across tests. The statistical methods for repeated measurements and multiplicity are not reported in the registry record.

The record lists 9 outcome measures and 0 analyses. Those counts do not identify which analyses were planned, whether all outcomes were analyzed, or how results were selected for reporting. No particular model, adjustment, or interim-analysis procedure should be inferred. The primary endpoint results themselves are not reported, so a recalculation from posted summary statistics is not possible.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, but the primary endpoint spans Day 1 and Day 14 and applies to the QD groups. The broader study also concerns pharmacokinetics, continuous intragastric pH, safety and tolerability. When several outcomes, time points, doses, or contrasts are examined, multiple statistical tests can increase the chance of at least one apparently unusual result. In general, a prespecified multiplicity strategy may address that issue. The multiplicity approach is not reported in the registry record.

The record lists 0 analyses. This does not establish whether analyses were conducted outside the registry, nor does it explain how the outcome measures were handled. A formal analysis plan, statistical model, treatment of repeated observations, and approach to any interim analyses are not reported in the registry record.

Missing-data handling is also not reported. The primary outcome population note says the analyzed count differs from participant-flow figures because of a discrepancy between completers and evaluable subjects related to protocol deviations. It mentions a participant in the 50 mg QD group who discontinued before completion of the ful—an incomplete description. The exact endpoint analysis counts, extent of missing primary measurements, and handling of missing values are not reported in the registry record.

These gaps limit interpretation of any comparison that might otherwise be made. The registry does not provide the primary estimates, analysis populations, or method details needed to assess how multiplicity and missing data affected results. It is therefore not possible to determine whether estimates are based on all randomized participants, evaluable participants, completers, or another population.

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% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: commotio cerebri (8.3%).

The safety summary reports serious adverse events by dose group. It records 0 serious events in the 25 mg QD, 50 mg QD, 75 mg QD, 25 mg BID and 50 mg BID groups, and 1 in the 75 mg BID group. The listed number at risk is 12, 13, 13, 12, 11 and 12 in those respective groups. The record reports 0 deaths in every listed group.

The top serious-event term is Commotio cerebri, with a reported value of 8.3%. The registry entries do not provide further clinical detail about this event. The other adverse-event counts are 6, 8, 6, 7, 6 and 5 across the same sequence of groups. These are counts, not measures of event severity or duration.

In general, adverse-event counts describe events recorded in the study and do not establish that a study drug caused them. Group counts should be read alongside the number at risk and the study’s duration and follow-up. The registry entries do not report comparative statistical tests for adverse events or additional details about attribution. These safety figures should not be interpreted as proof of a causal relationship or as a complete characterization of risk.

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

This record describes a completed Phase 1 study in healthy subjects that examined linaprazan glurate across QD and BID dose groups. Its primary pharmacokinetic question concerns mean linaprazan AUC from 0 to 24 hours on Day 1 and Day 14 in the QD groups. The study also aimed to assess intragastric pH, safety and tolerability. Those stated aims define what the study set out to examine; they do not, by themselves, establish what was observed.

The primary endpoint’s numerical results are not reported in the registry record. Without the reported means, standard deviations, analysis counts, or uncertainty estimates, it is not possible to describe the observed exposure level, its variability, or the precision of an estimate. The same record does not provide numerical pH results. No conclusion about a dose-related pattern or a difference between regimens can be drawn from the intervention labels alone.

The safety summary records serious adverse events and deaths by group, as well as counts of other adverse events. Such counts provide descriptive information about events recorded during the study, but do not by themselves establish causation or permit a complete comparison of safety across regimens. The study population is described as healthy subjects, so the record does not directly answer questions about outcomes in people being treated for GERD.

In general, a Phase 1 pharmacokinetic study can characterize exposure under the regimens studied, while broader conclusions require the relevant numerical results and an understanding of the analysis. Here, the registry entries support a description of design and the recorded safety counts, but not a conclusion about the size or precision of the primary pharmacokinetic result. The record also does not provide evidence to support a treatment recommendation.

13. Why This Trial Matters Statistically

This trial is statistically notable for the kind of question it asks: it focuses on drug exposure at more than one assessment day and across once-daily dose groups, within a broader study that includes twice-daily schedules and continuous intragastric pH monitoring. Those features make clear why a study report needs to specify its target endpoint, analysis population, and intended comparisons. A study design and a list of outcomes are not substitutes for outcome estimates.

The registry explicitly flags a difference between completers and evaluable subjects in the primary analysis population, associated with protocol deviations. That distinction is important for interpreting continuous outcomes: the observations included in an analysis determine what population the reported mean describes. Reporting the analysis counts, exclusions, missing measurements, and handling of those measurements would make the endpoint easier to assess.

The record also illustrates the role of uncertainty reporting. A mean and standard deviation are named as the summary for the primary measure, but no numerical results are reported in the registry entries. Without estimates and precision measures, readers cannot judge whether observed exposure is tightly or widely distributed, or how reliably groups can be compared.

Finally, a study with multiple outcomes and measurement occasions raises general questions about prespecified analyses and multiplicity. Those methods are not reported in the registry record. The main statistical lesson is therefore about the boundary between design information and evidence: the record identifies the planned measurement and groups, but does not supply the primary outcome statistics needed to evaluate the result.

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 most consequential limitation is that numerical results for the primary endpoint are not reported in the registry record. Although the endpoint is defined by measure, unit, population and assessment days, the mean, standard deviation, analysis count and uncertainty are absent. The primary exposure findings therefore cannot be quantified or compared from these registry entries.

The outcome population description is incomplete and notes a discrepancy between completers and evaluable subjects related to protocol deviations. It also contains a truncated statement about a participant in the 50 mg QD group discontinuing before completion of the ful. The full discontinuation detail, analyzed counts and handling of any missing measurements are not reported in the registry record.

The study is described as open label and randomized, but the method of randomization and any allocation concealment are not reported. The detailed statistical plan, analysis model, multiplicity approach, and treatment of repeated measurements are also not reported. The registry entries do not state the rationale for the enrollment target or whether interim analyses were conducted.

Interpretation is further limited because the population is described as healthy male and female subjects, even though GERD is listed under conditions. The registry entries do not report numerical pharmacodynamic results for intragastric pH. Safety information is presented as counts, without reported comparative analyses or additional details about event attribution. These gaps restrict interpretation to the design and descriptive counts that are recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Investigate Linaprazan Glurate/Linaprazan in Healthy Subjects — NCT05742984.
• Registry record last updated 2025-05-07; status last verified 2025-05.
• Results first posted 2025-05-07.
• 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

The registry record identifies NCT05742984 as a completed Phase 1, randomized, open-label, parallel-group, single-center study of linaprazan glurate in healthy subjects. It lists an enrollment of 75, a start date of 2023-01-26 and a primary completion date of 2023-03-24.

The listed regimens include 25 mg, 50 mg and 75 mg doses administered QD or BID. The primary endpoint is mean linaprazan AUC0-24h in QD groups on Day 1 and Day 14, summarized with standard deviation. Numerical primary results are not reported in the registry record. The study’s broader aims include continuous intragastric pH measurement, safety and tolerability.

The safety summary records 1 serious adverse event in the 75 mg BID group, 0 serious events in the other listed groups, and 0 deaths across groups. The primary analysis population note describes a discrepancy between completers and evaluable subjects related to protocol deviations. Further analysis details and missing-data methods are not reported in the registry record.