A Study of Creon (Pancrelipase) in Resected and Non-resected Pancreatic Cancer Participants With Exocrine Pancreatic Insufficiency (EPI): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Creon (Pancrelipase) in Resected and Non-resected Pancreatic Cancer Participants With Exocrine Pancreatic Insufficiency (EPI) (NCT03859869), a randomized phase 4 study. The primary outcome is Change in Stool Fat From Baseline (Day 1) to Week 1 (Day 8) Among Participants With Resected Pancreatic Cancer.

2. Clinical Question

3. Trial Design

This was a Phase 4, randomized, parallel-design study sponsored by AbbVie. The registry lists quadruple masking and includes pancrelipase and placebo as interventions. The official title describes a double-blind randomized design with two dose cohorts in resected participants and an open-label single-dose cohort in non-resected participants. The non-resected high-dose cohort is explicitly described as open-label; the resected cohorts are the part of the study described as randomized and masked.

In the resected group, one cohort was assigned low-dose pancrelipase and another received high-dose pancrelipase. The low-dose description says participants would be evaluated at Weeks 1, 5, or 9 and that participants meeting criteria for dose increase would be given an increased dose, but the registry description is incomplete about what followed. The high-dose description says participants would continue high-dose pancrelipase throughout the study. It also mentions placebo being used as needed to keep pill counts alike, though that description is truncated. Further operational details are not reported in the registry record.

The non-resected group received high-dose pancrelipase throughout the study in an open-label cohort. This cohort does not provide a masked comparison in the posted primary outcome. The study began on 2020-02-25, and primary completion was recorded as 2022-03-23. Its status is TERMINATED. The reason for termination is not reported in the registry record.

Registry enrollment is listed as 1. The posted primary outcome has one participant in the resected high-dose arm and none in the resected low-dose arm. The registry record does not explain why the enrollment and outcome records are so limited or describe recruitment and follow-up in further detail.

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: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Neither the Resected Participants Receiving Low Dose Pancrelipase group nor the Non-Resected Participants Receiving High Dose Pancrelipase group enrolled any participants.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Participants who received at least one dose of study drug and who had evaluable stool fat at both Baseline and Week 1 visits

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: Full Analysis Set: all randomized participants who received at least 1 dose of study drug

6. Primary Endpoint

The registry lists the primary outcome as Change in Stool Fat From Baseline (Day 1) to Week 1 (Day 8) Among Participants With Resected Pancreatic Cancer, measured over Baseline (Day 1), Week 1 (Day 8).

The primary endpoint is the change in stool fat from baseline, on Day 1, to Week 1, on Day 8, among participants with resected pancreatic cancer. Stool fat is a continuous measure reported in g/24 hours. The registry says stool samples were collected during the 48 hours before both visits and analyzed for fat content. The outcome population included participants who received at least one dose of study drug and had evaluable stool-fat measurements at both visits.

As a general statistical rationale, measuring stool fat gives a quantitative way to describe fat content in stool over a defined collection period. A change endpoint focuses on how the measured value differs across the specified visits, rather than reporting only a value at one visit. It can therefore describe within-participant movement over time, provided measurements are available at both visits and the change is defined consistently.

The registry reports a value of 3.1 g/24 hours for the single participant in the resected high-dose arm. It does not report separate baseline and Week 1 measurements or the calculation convention for the change. Consequently, the numeric value cannot by itself establish the direction or size of the underlying stool-fat trajectory beyond the recorded change value. No result is reported for the resected low-dose arm.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean represent?

As a general statistical concept, a mean is an average of measured values. For a continuous endpoint such as stool fat, it gives a concise description of the observed group. It does not reveal whether all participants had similar values or whether observations differed substantially. That is why a dispersion measure is useful alongside the mean.

The registry identifies standard deviation as the planned dispersion measure for the primary outcome, but no standard deviation is posted. With only one observed participant in the resected high-dose arm, the record cannot characterize between-participant variability. There is also no low-dose outcome result from which to calculate a group mean or compare group averages.

What would a confidence interval add?

As a general explanation, a confidence interval describes the uncertainty around an estimate under a specified statistical method. It helps readers distinguish a point estimate from the range of values reasonably compatible with the data and method. No confidence interval is reported for this primary outcome. The available record does not support a reliable estimate of the difference between the resected dose groups, so an interval for that contrast is not available either.

Why is the randomized comparison not estimable?

Random allocation is intended to make treatment groups comparable on average, including with respect to factors that may not be measured. That design feature does not replace the need for outcome observations in both groups. Here, the resected high-dose arm has one primary outcome observation and the resected low-dose arm has none. Without observed outcomes in both arms, the treatment contrast cannot be calculated from the posted results.

Masking can reduce the influence of expectations on care, measurement, or assessment. The registry lists quadruple masking and describes a double-blind randomized design for the resected dose cohorts. It separately describes the non-resected cohort as open-label. The registry record does not explain exactly who was masked in the resected cohorts or how masking was implemented beyond the available descriptions.

What does the change endpoint measure?

As a general concept, a change endpoint compares a participant's value at a follow-up visit with that participant's value at baseline. It can account for the starting value in describing the observed trajectory. Interpretation depends on the exact subtraction convention, the timing and quality of measurements, and complete paired observations. The registry names baseline as Day 1 and follow-up as Week 1, Day 8, and describes stool collection before each visit. It does not report the separate visit values or state the arithmetic convention used for the change.

The stated outcome population requires a dose of study drug and evaluable stool-fat observations at both visits. This is a complete-pair requirement for the primary endpoint: a participant without an evaluable measurement at either visit would not meet that definition. The record does not report how many participants were assessed for eligibility for this population, how many had missing measurements, or how missing measurements were handled in any analysis.

What can be said about statistical testing?

The registry record lists zero analyses and no inferential result for the primary outcome. There is no reported p-value or confidence interval for a dose comparison. A p-value, as a general statistical concept, evaluates how compatible observed data are with a specified null model, under the assumptions of the analysis. It does not measure the probability that a treatment works, and it cannot be interpreted when no corresponding analysis is reported.

Statistical significance is not the only concern. Estimation of the size and precision of an effect is also important. The single posted value has no reported variability measure, and the comparison arm has no outcome observations. Thus, the record gives neither a precise estimate of a comparative effect nor a basis for judging whether any observed change is unusual relative to variation.

How should planning calculations be understood?

As a general principle, sample-size calculations are planning tools based on assumptions about an effect, variability, allocation, significance level, and analysis method. They are not measures of what a completed study actually demonstrated. The registry's planning illustration assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. The record does not provide a usable two-arm observed effect for the primary endpoint, and the comparison is marked as not estimable. No planning number should be interpreted as observed power or as evidence about the treatment effect.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes. The secondary outcomes concern change in average daily stool frequency from baseline to Week 1, change in stool consistency from baseline to Week 1, and change in the total exocrine pancreatic insufficiency symptoms score from baseline to Week 1, all among participants with resected pancreatic cancer. These outcomes create multiple opportunities to examine results. As a general statistical concern, testing several outcomes can increase the chance of obtaining an apparently notable result by chance unless the analysis plan addresses multiplicity.

Multiplicity procedures, a prespecified testing hierarchy, and any adjustment to significance thresholds are not reported in the registry record. The record does not report interim analyses or a statistical analysis plan. No inferential analyses are posted, so there are no reported p-values to evaluate for multiplicity in any case.

The primary outcome population requires participants to have received at least one dose and to have evaluable stool-fat measurements at both baseline and Week 1. The registry does not report the number screened, the number with missing measurements, the reasons for missingness, or how missing data were handled. It also does not report whether all randomized participants were included in an analysis population or whether any other analysis sets were defined.

These omissions matter because restricting an analysis to participants with complete measurements can affect how representative the analyzed group is of the randomized population. As a general point, missingness can introduce bias when the chance that an observation is missing is related to participant characteristics or outcomes. The registry record does not provide enough information to assess whether that concern arose in this study.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

For the resected high-dose pancrelipase group, the registry lists one participant at risk for serious adverse events and zero affected by serious adverse events. It lists one participant at risk for other adverse events and one affected. Deaths are listed as zero. The record does not identify the type or term of the other adverse event; serious adverse-event terms are not listed.

The resected low-dose group and the non-resected high-dose group each have zero participants listed at risk in the posted safety figures, with zero affected and zero deaths. These zero-at-risk entries do not establish that no events could occur in those groups; they indicate that no participants are represented in those safety denominators in the record.

As a general statistical caution, adverse-event counts are descriptive and depend on the number of participants observed and the period of observation. A count in a very small group is not a stable estimate of the frequency expected in a broader population. The registry figures alone do not establish whether an event was caused by study treatment. The reason for termination and any further safety context are not reported in the registry record.

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

The posted result documents a stool-fat change value of 3.1 g/24 hours for one resected participant receiving high-dose pancrelipase. It also documents that no resected low-dose participant has a primary outcome result in the record. This is a description of limited recorded data, not an estimable comparison between doses.

The result does not establish the typical change among resected participants, because only one high-dose outcome is available and no low-dose outcome is available. It does not quantify uncertainty around a comparative effect, because there is no reported confidence interval, dispersion estimate, or inferential analysis. The record does not provide baseline and Week 1 values separately, so the recorded change cannot be unpacked into the underlying measurements.

The result does not answer the primary question for the non-resected cohort. That cohort was open-label and is not the population specified for the primary outcome. No primary outcome result for non-resected participants is posted. The result also cannot be generalized to participants who do not meet the stated primary outcome population definition.

As a general principle, statistical evidence about treatment contrasts requires outcome data from the groups being compared and an analysis that accounts for uncertainty. A trial's randomized and masked design may be relevant to interpreting such a contrast, but design labels alone do not provide outcome evidence. Here, the posted data are too sparse to determine the size, precision, or direction of a comparative effect.

The TERMINATED status does not explain why the study stopped. That reason is not reported in the registry record. The outcome and safety figures should therefore be read as the available recorded observations, without inferring a cause for termination or a treatment conclusion.

13. Why This Trial Matters Statistically

This study illustrates an important distinction between a trial's planned design and the evidence that can be estimated from its recorded outcomes. Randomization and masking are features intended to strengthen a comparison, but they do not ensure that usable outcomes are available in each group. In this record, one resected high-dose participant and no resected low-dose participants contribute primary outcome data. The randomized comparison is consequently not estimable from the posted results.

The case also shows why an outcome mean should be read with its sample size and uncertainty information. The recorded mean of 3.1 g/24 hours is an observed value for one participant, not a dependable description of a group distribution. With no spread measure and no comparator outcome, readers cannot assess how variable the outcome might be or how precisely a dose difference is estimated.

The trial's structure includes both a resected randomized design and an open-label non-resected cohort. Those populations and designs address distinct questions; results from one cannot automatically stand in for the other. The primary outcome is defined only for resected participants, while the non-resected cohort has no posted primary result.

Finally, the record highlights the difference between reporting an endpoint and reporting an analysis. A named primary measure and stated assessment times do not on their own provide a treatment estimate, uncertainty interval, or test. For statistical interpretation, the number of observed outcomes, the analysis population, missing-data handling, and inferential results are all consequential. Several of these details are not reported in the registry record.

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 main limitation is the extremely sparse primary outcome record: one participant is reported in the resected high-dose arm and none in the resected low-dose arm. This precludes a direct estimate of the randomized dose comparison. The reported mean has no accompanying standard deviation or interval, and the record gives no separate baseline and follow-up stool-fat values.

Registry enrollment is listed as 1, but the record does not explain how enrollment relates to the resected and non-resected cohorts or to the safety denominators. There is no posted primary outcome for the non-resected cohort. The registry record also does not report the reason for termination, recruitment details, follow-up completeness, or reasons for missing outcome data.

Although the registry describes randomized and masked resected cohorts, details of allocation implementation and masking are not reported in the registry record. The low-dose description refers to evaluation and possible dose increase at Weeks 1, 5, or 9 but is incomplete. The high-dose arm description is also truncated. The available text therefore does not support a complete reconstruction of dosing procedures or trial conduct.

No analysis is posted, and the registry does not report a statistical analysis plan, interim analyses, multiplicity approach, or missing-data method. These omissions prevent assessment of whether outcome analyses followed prespecified methods. The limited outcome data would constrain comparative inference even if those methods were available.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Creon (Pancrelipase) in Resected and Non-resected Pancreatic Cancer Participants With Exocrine Pancreatic Insufficiency (EPI) — NCT03859869.
• Registry record last updated 2023-06-05; status last verified 2023-06.
• Results first posted 2023-06-05.
• 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

NCT03859869 is a Phase 4, randomized, parallel-design study of pancrelipase in pancreatic cancer participants with exocrine pancreatic insufficiency. It included resected low- and high-dose cohorts and an open-label non-resected high-dose cohort. The study began on 2020-02-25, had primary completion on 2022-03-23, and is listed as TERMINATED.

The primary endpoint was change in stool fat from baseline on Day 1 to Week 1 on Day 8 among resected participants with evaluable measurements at both visits. The posted result is 3.1 g/24 hours for one resected high-dose participant; the resected low-dose arm has no reported primary outcome participants. A comparative effect is not estimable. The registry lists zero analyses. The reason for termination, missing-data handling, and further analysis-plan details are not reported in the registry record.