Pancreatic Enzyme Replacement and Glucose Regulation in Type 1 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pancreatic Enzyme Replacement and Glucose Regulation in Type 1 Diabetes (NCT05266963), a randomized early/phase 1 study. The primary outcome is Improvement in Glucose Regulation.

2. Clinical Question

3. Trial Design

This was a randomized, quadruple-masked, crossover study of CREON and placebo in type 1 diabetes. The registry lists the phase as EARLY PHASE1 and the enrollment as 11. The study is marked completed, with a start date of 2022-09-02 and a primary completion date of 2024-03-22. Those dates describe the registry record; they do not by themselves indicate when each participant received treatment or how long each treatment period lasted.

In a crossover study, participants receive more than one study treatment in an assigned order. This structure can support comparisons within the same participant, because each person may contribute observations under each treatment condition. Such comparisons can be useful when participant-level characteristics affect outcome measurements. At the same time, interpretation can depend on treatment order, changes over time, and whether an earlier treatment affects outcomes measured during a later period. Those are general design considerations, not claims about what occurred in this study.

The registry says that five of the participants in the primary analysis population received CREON followed by placebo, while five received placebo followed by CREON. It identifies those 10 participants as the people who completed both drug periods. The enrolled population and the primary analysis population therefore have different reported counts; the registry does not explain the status or analysis of the remaining enrolled participant.

The study description says the treatments were given in a random order, and the record labels allocation as randomized and masking as quadruple. It does not describe the randomization procedure, the identities of the masked parties, or whether masking was assessed. Details of the treatment schedule, any washout, adherence, and the statistical handling of period and sequence effects are not reported in the registry record. The design labels establish the broad structure, but they do not supply those operational details.

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: Eleven (11) participants were enrolled to achieve completion goal of ten (10). One subject withdrew at end of drug period A due to failed OGTT and unwillingness to continue.

Drug Period A

Reasons for not completing this period:

Washout

Drug Period B (Crossover)

Analysis population for the primary outcome, as defined in the registry: This analysis population is the 10 participants who completed both drug periods of the study. Five received CREON, then placebo, and the other five received placebo, then CREON.

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: Although 11 participants were enrolled, only 10 completed both treatment periods, so those 10 are the only ones included in analysis.

6. Primary Endpoint

The registry lists the primary outcome as Improvement in Glucose Regulation, measured over through study completion (4-5 weeks).

The primary endpoint is glucose regulation assessed using C-peptide area under the curve (AUC) during mixed meal tolerance testing. The registry specifies the unit as ng*hr/mL and describes the summary parameter as a mean with full-range dispersion. Testing is described at baseline and after treatment with placebo and CREON. The stated timeframe is through study completion (4-5 weeks).

AUC is a way to represent the integrated measurements across a testing interval, rather than relying on a single measurement at one moment. In general, this can characterize the overall response observed during a test. C-peptide is the marker specified in this trial's endpoint; the registry does not provide a more detailed explanation of how individual measurements were collected or how the AUC was calculated.

The endpoint is relevant to the study's stated question because the investigators set out to assess glucose regulation after enzyme replacement compared with placebo. However, an endpoint definition is not itself an outcome finding. The registry record does not report the AUC estimates, a treatment contrast, a confidence interval, or a single comparison result for this primary outcome. Consequently, the direction and precision of any treatment difference cannot be evaluated from the posted primary outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies this study as randomized, quadruple-masked, and crossover. Those terms describe important parts of the design, but the registry does not report a complete statistical analysis plan. The following explanations distinguish general statistical concepts from the specific methods that are documented for this trial.

What does randomization contribute?

In general, random assignment is intended to make treatment allocation independent of participants' measured and unmeasured characteristics. In a crossover trial, the assigned order determines which treatment is received first. Randomization can help prevent systematic differences between treatment-order groups, but it does not guarantee that every characteristic will be balanced in a small study. The registry labels allocation as randomized and says the order was random; it does not report the sequence-generation method, allocation concealment, or implementation details.

How does a crossover comparison work?

In a crossover design, a participant receives each treatment at different times. A within-participant comparison can reduce the influence of stable characteristics, because the participant serves as their own comparator. This is a general feature of the design, not a statement about the magnitude or validity of a treatment effect in this study. Crossover analyses also need to consider whether outcomes change over time, whether treatment effects vary by period, and whether an earlier treatment has effects that persist into a later period. The registry does not report a washout interval or a method for assessing or adjusting for these possibilities.

The primary analysis population is described as the 10 participants who completed both drug periods. Five followed the CREON-then-placebo order and five followed the placebo-then-CREON order. This gives the reader information about the analyzed treatment sequences, but not about the statistical model used to compare them. The registry does not report whether the analysis was based on paired differences, a model including period and sequence, or another approach.

What does the endpoint summary mean?

The primary endpoint is C-peptide AUC, measured during mixed meal tolerance testing and expressed in ng*hr/mL. The record describes the parameter as a mean and the dispersion as a full range. In general, a mean summarizes the center of observations, and a range communicates the observed spread. These summaries answer different questions from a confidence interval. A confidence interval for a treatment contrast would describe the range of effect estimates compatible with the data under the model's assumptions, and would help show how precise the estimate is. The registry does not report such an interval for a single primary comparison.

The AUC measure integrates information across measurements during the testing interval. In general, this can summarize the overall pattern across that interval, but its interpretation depends on how measurements were timed and how the area was calculated. The registry does not give the sampling schedule, calculation details, or individual outcome values. Therefore, the endpoint definition can be described, but the numerical outcome cannot be reconstructed from the record.

What does the planning illustration represent?

The sample-size assumptions describe a planning illustration computed from the observed effect, not the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, a planning calculation estimates the sample size that would be needed under a set of assumptions to achieve a target probability of detecting a specified effect if that effect were true. It is not a measure of the probability that the trial's result is correct, and it is not observed power.

The registry says that time-to-event illustrations use total events, while other illustrations use participants per arm. The primary endpoint is not a time-to-event outcome. Regardless, those planning assumptions do not establish the sample-size rationale for the completed study. The original sample-size justification is not reported in the registry record. The numerical illustration should be treated as hypothetical planning information, not as a feature of the trial's original analysis plan.

What can be said about significance and uncertainty?

A p-value, when reported, measures how compatible the observed data are with a specified null model and analysis assumptions; it is not the probability that a treatment works or that the null hypothesis is true. A confidence interval describes uncertainty around an estimate and is especially useful for assessing the range of effects compatible with the data. Neither a p-value nor a confidence interval for a single primary treatment contrast is reported in the registry record. Without the estimate and its uncertainty, statistical significance and precision cannot be assessed.

The record reports two outcome measures and two analyses, while the primary outcome description notes several categories or time points that were not reduced to one comparison. In general, multiplicity arises when several outcomes, time points, or analyses are considered, because the chance of a false-positive finding can increase if many tests are interpreted without an appropriate plan. The record does not report a multiplicity adjustment or identify how multiple comparisons were prioritized. It is therefore not possible to determine from the registry which testing strategy was used.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses, and the primary outcome description says that it has several categories or time points and was not reduced to one comparison. In general, examining multiple outcomes, time points, or contrasts can make interpretation more difficult. If many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or which contrasts were designated for formal inference.

The primary analysis population is explicitly described: the 10 participants who completed both treatment periods. The record also lists enrollment as 11, but does not explain the difference between enrollment and the primary analysis population. It does not report why the other enrolled participant is not part of the stated population, whether any data from that participant were analyzed, or whether an alternative analysis population was used.

Missing-data handling is not reported in the registry record. The record does not say whether missing measurements were imputed, excluded, or handled through a statistical model, nor does it describe sensitivity analyses. In a crossover study, incomplete treatment sequences can affect which participants contribute to a paired comparison; the registry does not describe whether participants with incomplete periods were considered in any analysis.

These gaps do not establish that the underlying investigators failed to consider multiplicity or missing data. They mean the public registry information does not allow readers to evaluate those decisions. The record's stated complete-period population is clear, but the path from enrollment to analysis, and the implications of unreported or unavailable measurements, are not documented.

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 0% reporting threshold.

The registry reports adverse-event figures separately for CREON and placebo. For each treatment group, 10 participants are listed as at risk for serious adverse events and 10 as at risk for other adverse events. The reported number affected is zero for serious adverse events and zero for other adverse events in each group. Deaths are also reported as zero in each group, and no leading serious adverse-event terms are listed.

These figures describe what the registry reports for the study; they should not be read as proof that an event is impossible or that no risk exists. In general, an observed count of zero in a small study can coexist with uncertainty about the underlying event rate. A larger or longer study may provide different information, but the registry record does not report evidence that permits quantifying that uncertainty.

The record does not provide further detail about how adverse events were defined, collected, attributed, or monitored, or whether the safety summaries cover exactly the same participants as the primary outcome analysis population. The at-risk counts and zero affected counts are the posted safety results, not a complete account of all safety procedures or possible risks.

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

The record establishes that a randomized, quadruple-masked crossover study compared CREON with placebo in type 1 diabetes and assessed glucose regulation through C-peptide AUC during mixed meal tolerance testing. It also states that the primary analysis population included the 10 participants who completed both treatment periods, divided between the two treatment orders. These details describe the study question and the population used for the stated primary analysis.

The registry does not report a single numerical primary comparison. It does not provide the treatment-specific AUC summaries, an estimated contrast, a confidence interval, or a p-value. As a result, the posted results do not show the direction or size of a difference in the primary endpoint, or how precisely such a difference was estimated. No conclusion about an outcome favoring either treatment can be drawn from the endpoint description alone.

The record's statement that the primary outcome has several categories or time points and was not reduced to one comparison is important. A general description of measurements is not interchangeable with a prespecified, interpretable estimate. Readers would need a clearly defined contrast and its uncertainty to assess what the comparison says about the study question. Those results are not reported in the registry record.

The study's stated hypothesis also mentions hypoglycemia and symptoms of pancreatic exocrine insufficiency. The material available in the registry record does not give detailed results for those hypotheses. The adverse-event summary reports zero serious adverse events, zero other adverse events, and zero deaths in each treatment group, but that safety summary is not the same as an efficacy result for glucose regulation or symptoms.

Thus, the record is informative about trial structure, the primary endpoint, the completed-period analysis population, and the posted adverse-event counts. It is not sufficient to determine whether CREON changed the measured outcome compared with placebo, what the magnitude of any difference was, or whether a difference was estimated precisely. Those questions require outcome estimates and analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because it uses a crossover design to compare a pancreatic enzyme replacement with placebo in people with type 1 diabetes. In general, crossover designs can make within-participant contrasts possible, which may be useful when individuals differ in their baseline measurements. They also make treatment order, time effects, and possible carryover relevant to interpretation. The registry labels the design but does not report how these issues were handled analytically.

The study also illustrates why a clearly reported endpoint contrast matters as much as an endpoint label. C-peptide AUC is named, its unit and summary format are specified, and the testing context is described. Yet the record says the primary outcome has several categories or time points and is not reduced to one comparison. Without one interpretable estimate and its uncertainty, the endpoint definition cannot answer the comparative question on its own.

The stated analysis population further highlights the distinction between enrollment and analysis. The registry records enrollment of 11 and identifies 10 completers as the primary analysis population, but does not explain the status of the remaining enrolled participant or how missing data were handled. Clear accounting of participant flow and analysis populations helps readers understand which observations support an estimate.

Finally, the planning illustration is explicitly based on the observed effect and on stated assumptions. Keeping a planning calculation separate from the original trial design and from observed inference is important: it cannot substitute for the treatment estimate, confidence interval, or p-value. The record offers a useful description of the intended comparison, but its missing primary result limits what can be learned statistically from the posted information.

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 central limitation for interpreting the primary question is that the registry record does not report a single reduced comparison for the primary outcome. Although it identifies C-peptide AUC, the testing context, unit, summary type, and analysis population, it does not provide numerical outcome estimates or an uncertainty interval. The direction, magnitude, and precision of any treatment contrast are therefore unavailable in the posted results.

The outcome is described as having several categories or time points. The registry does not specify which contrast was intended to be the principal inferential comparison, how baseline was used in the analysis, or how multiple comparisons were handled. The record also does not report a statistical model, treatment of period or sequence, or procedures for evaluating possible carryover in the crossover design.

The primary analysis population is defined by completion of both drug periods, while enrollment is reported separately. The registry does not explain the participant accounting between these figures, why the analysis population excludes one enrolled participant, or how incomplete or missing measurements were treated. It is also unclear whether any additional analysis populations or sensitivity analyses were used.

Further design details are not reported, including the treatment-period schedule, any washout interval, adherence information, and operational details of randomization and masking. These omissions do not show that such procedures were absent; they limit what can be assessed from the public record. The posted safety counts are also limited: detailed event definitions, collection methods, and attribution procedures are not described.

Finally, the registry's sample-size assumptions are presented as a planning illustration based on the observed effect, not as the trial's original design justification. The original sample-size rationale is not reported. Together, these reporting gaps mean that the trial's comparative primary result and several aspects of its analysis cannot be independently evaluated from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pancreatic Enzyme Replacement and Glucose Regulation in Type 1 Diabetes — NCT05266963.
• Registry record last updated 2025-03-28; status last verified 2025-03.
• Results first posted 2025-03-28.
• 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.

18. Record Summary

The registry record describes NCT05266963, titled “Pancreatic Enzyme Replacement and Glucose Regulation in Type 1 Diabetes.” It lists the study as EARLY PHASE1, randomized, quadruple-masked, crossover, and completed. Enrollment is 11; the listed start date is 2022-09-02 and primary completion date is 2024-03-22.

The study compared CREON, described as a pancreatic enzyme replacement, with placebo. The primary endpoint was C-peptide AUC during mixed meal tolerance testing, reported in ng*hr/mL, with a mean and full-range dispersion. The primary analysis population was the 10 participants who completed both periods, split evenly between the two treatment orders.

The registry does not report a single primary comparison or its numerical estimate and uncertainty. Safety summaries list zero serious adverse events, zero other adverse events, and zero deaths in each treatment group. The record does not report the statistical plan, missing-data methods, or multiplicity handling.