A Randomized, Double-Blind, Dose Response-Control, Crossover Study to Evaluate the Safety and Efficacy of Two Doses of EUR-1008 (APT-1008) in Chronic Pancreatitis (CP) Participants With Exocrine Pancreatic Insufficiency (EPI): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomized, Double-Blind, Dose Response-Control, Crossover Study to Evaluate the Safety and Efficacy of Two Doses of EUR-1008 (APT-1008) in Chronic Pancreatitis (CP) Participants With Exocrine Pancreatic Insufficiency (EPI) (NCT00788593), a randomized phase 3 study. The primary outcome is Percent Coefficient of Fat Absorption (CFA) of Participants Treated With High Dose EUR-1008 and Low Dose EUR-1008.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, triple-masked, dose-response-control crossover study of EUR-1008 (APT-1008) in participants with chronic pancreatitis and exocrine pancreatic insufficiency. The interventions listed were placebo, high-dose EUR-1008, and low-dose EUR-1008. The primary objective focused on the high-dose versus low-dose comparison, rather than a stated primary comparison with placebo.

The registry reports enrollment of 82 participants. The primary endpoint concerns hospital treatment during the first and second intervention periods, and its timeframe is 3 to 5 days of hospital treatment in those periods. The record does not describe the intervention sequence, the length or use of any washout period, or the dose amounts. Those details are important for understanding a crossover trial, but are not reported in the registry record.

In a crossover design, participants can receive different interventions in separate periods, allowing comparisons to draw on within-participant information. That feature can affect how results should be analyzed, because outcomes from the same participant may be related. The registry identifies the model as crossover and reports ANCOVA for the primary comparison, but does not describe the full statistical model or its covariates.

The primary analysis population is described as the FAS, which included participants who received at least one dose. For this endpoint, the reported number analyzed means participants with CFA values available. The posted primary summaries show 72 participants for each dose group. The record does not explain why these analysis counts differ from enrollment or provide a detailed account of participant flow by period.

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.

Placebo Run-in Phase

Reasons for not completing this period:

First Intervention Period

Reasons for not completing this period:

Second Intervention Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS included all participants who received at least 1 dose of the study medication. Here "N" (number of participants analyzed) signifies those participants for whom the CFA values were available.

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 (FAS) included all participants who received at least 1 dose of the study medication.

6. Primary Endpoint

The registry lists the primary outcome as Percent Coefficient of Fat Absorption (CFA) of Participants Treated With High Dose EUR-1008 and Low Dose EUR-1008, measured over 3 to 5 days of hospital treatment in first and second intervention periods.

The primary endpoint is percent coefficient of fat absorption, or CFA. It measures the proportion of dietary fat absorbed rather than excreted. The registry describes its calculation as fat intake minus fat excretion, divided by fat intake, multiplied by 100. Fat excretion was determined from stool collected during a 72-hour CFA determination period. The reported measure is the mean percent CFA calculated over 3 to 5 days of hospital treatment in the first and second intervention periods.

CFA is used in this trial as a measure of fat absorption relevant to malabsorption in participants with exocrine pancreatic insufficiency. It is a continuous measure, so the primary summaries report group means and standard deviations, and the main comparison is expressed as a mean difference. The registry’s primary efficacy objective is to evaluate the difference between high-dose and low-dose EUR-1008.

The measure captures fat absorption over a specified collection and treatment period. It is not, by itself, a complete description of symptoms, nutritional status, or longer-term outcomes. The registry lists secondary outcomes addressing nitrogen absorption, weight, and body mass index, but their inclusion does not change the definition of the primary endpoint. The record does not report a threshold for what size of CFA difference would be clinically important.

7. Results Posted in the Registry

• EUR-1008 (APT-1008) High Dose: mean 89.86 versus 88.87 on control; difference 0.99 (95% CI -2.53 to 4.51), standardized effect d = 0.09; z-test p = 0.581.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Placebo Baseline in Weight at End of Each Treatment Period

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • EUR-1008 (APT-1008) High Dose: mean 0.50 versus 0.38 on control; difference 0.12 (95% CI -0.28 to 0.52), standardized effect d = 0.10; z-test p = 0.557.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between EUR-1008 (APT-1008) High Dose and the control. The interval gives the range of effects that remain compatible with the data.

Change From Placebo Baseline in Body Mass Index (BMI) at End of Treatment

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • EUR-1008 (APT-1008) High Dose: mean 0.16 versus 0.13 on control; difference 0.03 (95% CI -0.10 to 0.16), standardized effect d = 0.07; z-test p = 0.651.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between EUR-1008 (APT-1008) High Dose and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering CFA by dose, nitrogen absorption, weight, and body mass index. The posted numerical summaries in the available results include weight and body mass index comparisons between high- and low-dose EUR-1008. Their estimates are small in the units reported, and their unadjusted confidence intervals include zero. This broad pattern does not provide a clear, precise secondary contrast that changes the interpretation of the primary CFA result.

The secondary outcomes address related but distinct measures. Weight and body mass index reflect different aspects of participant status than CFA, while nitrogen absorption is another absorption measure. The listed secondary outcomes may help describe a wider set of results, but they should not be treated as interchangeable with the primary endpoint. Numerical results for the listed nitrogen absorption outcome and the additional CFA outcome are not reported in the registry record.

Secondary results generally carry less weight than the primary analysis when many outcomes or comparisons are examined. In general, testing multiple outcomes raises the chance that some appear notable by chance, particularly when no adjustment for multiplicity is made. The registry record does not report a multiplicity procedure or clarify which secondary analyses were prespecified as confirmatory. The secondary estimates should therefore be read as supportive or exploratory evidence, not as independent confirmation of a primary conclusion. Their uncertainty and the absence of reported multiplicity handling limit how much they can add to the primary comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Placebo Baseline in Percent Coefficient of Fat Absorption (CFA) in High Dose EUR-1008 and Low Dose EUR-1008 During Hospital Treatment
• Change From Placebo Baseline in Percent Coefficient of Nitrogen Absorption (CNA) During Hospital Treatment
• Change From Placebo Baseline in Weight at End of Each Treatment Period
• Change From Placebo Baseline in Body Mass Index (BMI) at End of Treatment

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference describe?

The endpoint is continuous, and the registry reports its mean in each dose group. A mean difference expresses the estimated separation between those group means. A positive estimate in this comparison means the estimated mean percent CFA is higher with high-dose than with low-dose EUR-1008. It describes an average contrast; it does not mean that every participant had a change of that size or in that direction.

The posted group summaries also include standard deviations. A standard deviation describes how dispersed participant values are around a group mean. It is not a confidence interval and does not directly give the uncertainty in the estimated difference. In the primary summaries, the low-dose mean is 88.87 with standard deviation 12.44, and the high-dose mean is 89.86 with standard deviation 8.77.

What is ANCOVA doing?

The registry reports an ANCOVA analysis and identifies its result as a least-squares mean difference. In general, analysis of covariance estimates a group contrast while accounting for covariates included in the model. The registry record does not name the covariates or give enough model detail to determine exactly how the adjustment was performed. Its reported estimate is 1.023, with a 95% confidence interval from -0.656 to 2.701 and p = 0.228.

The least-squares mean difference is not necessarily identical to the difference between the raw group means. It represents the contrast from the specified model, while the raw summaries describe the observed means. The registry’s ANCOVA result should therefore be kept distinct from the unadjusted recalculation based only on posted summary statistics. The record does not provide the model specification needed to reproduce the ANCOVA independently.

Why does crossover design matter?

In general, a crossover study can compare interventions within the same participant across different periods. This can account for stable participant characteristics in the comparison, but it also means outcomes across periods may be correlated. Period effects, treatment sequence, and any carryover between periods can matter to the analysis. These are general considerations, not claims about what occurred in this trial. The registry identifies a crossover model but does not report the sequence, washout details, or how period and carryover effects were handled.

The unadjusted recalculation is based on the posted group summaries and does not reproduce the sponsor’s ANCOVA. It also cannot incorporate participant-level pairing or other model details that are not available in those summaries. Accordingly, it is a supplemental descriptive comparison, not a substitute for the registry’s reported analysis. Because the record does not state the statistical model in sufficient detail, the relationship between its ANCOVA and all features of the crossover design cannot be assessed fully.

What do the p-values indicate?

In general, a p-value measures how incompatible the observed data are with a specified null hypothesis, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The registry reports p = 0.228 for the ANCOVA comparison. The summary-statistic recalculation reports an unadjusted p-value of 0.581. The latter is an unadjusted recalculation, whereas the former is the analysis posted in the registry record.

A p-value should be interpreted alongside the effect estimate, its confidence interval, the design, and the analysis population. Here the two estimates are small relative to the uncertainty expressed by their intervals, and both intervals include zero. That combination supports a cautious reading: the posted data do not precisely establish the size or direction of a difference between doses.

What can standard deviations and uncertainty tell us?

In general, greater variation among participant measurements can make a group contrast harder to estimate precisely, especially when sample sizes are limited. The standard deviations describe variation in measured CFA; the confidence intervals describe uncertainty around the estimated contrast. These answer related but distinct questions. The registry provides both raw group summaries and an ANCOVA interval, but does not provide participant-level measurements, the covariance between periods, or sufficient model details for a fuller statistical reconstruction.

The registry defines the FAS as participants who received at least one dose, and notes that the number analyzed for CFA means those with available values. This makes the endpoint-specific analysis count explicit, but does not describe how missing values were handled or whether any imputation was used. Those omissions matter when judging how well the analysis population represents everyone enrolled.

11. Confidence Intervals and Precision

The registry’s ANCOVA estimate is a least-squares mean difference of 1.023, with a 95% confidence interval from -0.656 to 2.701. The interval includes zero and extends to both negative and positive values, so the data are compatible with the high-dose mean being lower or higher than the low-dose mean under this analysis. Its range conveys uncertainty that is not captured by the point estimate alone.

The unadjusted recalculation gives a mean difference of 0.99, with a 95% confidence interval from -2.526 to 4.506. This interval is also compatible with differences in either direction and includes zero. It is wider than the ANCOVA interval. Because the analyses are not the same, the intervals should not be treated as interchangeable estimates from one identical method.

In general, a confidence interval describes a range of estimates reasonably compatible with the data and the method used. It is not a guarantee that the true effect lies inside this particular interval, nor does an interval including zero prove that there is no effect. Here, both intervals leave uncertainty about the direction and size of a dose contrast. The registry does not provide a threshold for a clinically important CFA difference, so statistical precision cannot be translated into a judgment about clinical importance.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations concern participants per arm, not total events. This is a continuous-outcome comparison, not a time-to-event calculation. The primary endpoint’s planning illustrations list 1,856 participants per arm for planning at 100% of the observed effect, 3,299 for planning at 75% of the observed effect, and 7,421 for planning at 50% of the observed effect for 80% power. The corresponding values for 90% power are 2,484, 4,416, and 9,935 participants per arm.

In general, a power target describes the chance that a study will detect an effect of the specified size under the planning assumptions, if that effect is present. The 80% and 90% columns therefore describe different planning targets; the higher target requires more participants for the same assumed effect. The effect fractions describe how large an effect the planning exercise assumes relative to the observed effect. A smaller assumed effect is harder to distinguish from random variation, so it requires more participants.

The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The planning exercise uses the observed effect as its starting point and then considers the stated fractions of that effect. The registry record does not report the trial’s original design assumptions or its own sample-size justification. These figures are planning illustrations based on the observed result, not observed power. The enrollment of 82 should not be compared with these illustrations as though they described the trial’s original plan.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.990; pooled standard deviation σ = 10.763.
2. n = 2 × (1.96 + 0.842)² × 10.763² / 0.990² = 1,855.2, rounded up to 1,856 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.989999999999995                      # observed difference in means
sigma <- 10.7625856558728                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(788593)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1,856 (80% power), 2,484 (90% power)
 75% of observed effect: n per arm = 3,299 (80% power), 4,416 (90% power)
 50% of observed effect: n per arm = 7,421 (80% power), 9,935 (90% power)
power.t.test: 1856.2 
Simulated power at n = 1,856 per arm: 0.796 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as an ANCOVA least-squares mean difference of 1.023, with a 95% confidence interval from -0.656 to 2.701 and p = 0.228. This is the analysis directly reported for the primary endpoint. It should be distinguished from the unadjusted recalculation from the posted means, which gives a mean difference of 0.99, a 95% confidence interval from -2.526 to 4.506, and an unadjusted p-value of 0.581.

The two estimates are close in direction and point estimate, but they come from different approaches and have different intervals and p-values. The sponsor’s analysis is an ANCOVA result; the recalculation uses summary statistics and cannot reproduce adjustments or crossover-model details that are not reported. The registry does not provide the covariates or full model specification. Because the registry reports no discrepancy between the posted analysis and recalculation, the recalculation serves as a supplementary check rather than a replacement for the reported ANCOVA.

Neither analysis establishes that the dose groups are equivalent. Both confidence intervals include zero, and both leave uncertainty about the magnitude and direction of the contrast. The sponsor’s analysis remains the primary reported result for this comparison.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary efficacy objective: comparing percent CFA between high-dose and low-dose EUR-1008. It also lists secondary outcomes concerning CFA, nitrogen absorption, weight, and body mass index. The record does not report whether a formal multiplicity adjustment was used across secondary outcomes, doses, or other analyses. Without that information, the secondary findings should be interpreted cautiously, because multiple statistical comparisons can increase the likelihood of apparently notable results occurring by chance.

The primary endpoint population is described as the FAS, including participants who received at least one dose. The registry adds that the CFA analysis count represents participants for whom CFA values were available. The posted primary summaries report 72 participants per dose group, while overall enrollment was 82. The registry does not provide a detailed participant flow explaining the difference between enrollment and endpoint-specific analysis counts, or whether missingness differed by treatment period or dose.

The record does not describe the method used to handle missing endpoint values, whether imputation was performed, or whether sensitivity analyses assessed the consequences of missing data. Those details are important because conclusions can depend on which participants contribute outcome measurements and on assumptions about unavailable measurements. The available description identifies the analysis population but is not enough to evaluate those assumptions.

The crossover design also raises questions about period and sequence handling. In general, a crossover analysis may need to account for within-participant association and possible period effects. The registry names ANCOVA but does not report its covariates, the specific model structure, or how period, sequence, or possible carryover were handled. The record also does not report interim analyses or a detailed statistical analysis plan. These items are not reported in the registry record and should not be inferred from the design label alone.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastrointestinal haemorrhage (1.4%), pyrexia (1.4%), obstruction gastric (1.3%), pancreatic pseudocyst (1.3%), bile duct obstruction (1.3%).

The registry reports serious adverse events affecting 2 participants among 82 at risk in the placebo-baseline group, 2 among 74 at risk in the low-dose group, and 2 among 75 at risk in the high-dose group. These are counts of affected participants as recorded for the listed groups. The record does not explain how the placebo-baseline group relates to the crossover periods or provide participant-level timing, so the group counts should be read in the registry’s stated group labels rather than as a reconstructed treatment sequence.

The record lists gastrointestinal haemorrhage and pyrexia at 1.4% each, and obstruction gastric, pancreatic pseudocyst, bile duct obstruction, and renal injury at 1.3% each among the top serious-event terms. These percentages are reported as listed; the registry information does not establish that any event was caused by a study intervention. Deaths are not reported in the registry record.

Serious adverse event summaries describe reported events in this study population, but they do not by themselves establish comparative safety or causation. The crossover design and group labels also require care when interpreting the counts. The figures should be considered as descriptive registry information, not as a complete account of all possible harms or event timing.

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

The primary result estimates the difference in mean percent CFA between high- and low-dose EUR-1008 during the specified hospital-treatment periods. The posted ANCOVA estimate is 1.023, and its 95% confidence interval ranges from -0.656 to 2.701. The interval includes zero and allows values on either side of it, so the result does not precisely determine the direction or size of the difference. The unadjusted recalculation reaches a similarly uncertain interpretation, although it uses a different method.

This result does not prove that the doses are equivalent, because a confidence interval that includes zero can still allow nonzero differences. It also does not establish that either dose is superior, because the registry’s reported ANCOVA comparison does not provide clear statistical evidence of a difference. The registry record does not report a threshold for a clinically important CFA difference, so the estimated contrast cannot be judged against such a threshold from the information available.

The endpoint is a measured absorption outcome over a defined collection and treatment period. It is not a direct measure of every symptom or longer-term consequence associated with malabsorption. The trial also lists secondary outcomes, but the primary finding should not be generalized to outcomes for which numerical results are not reported or to populations not described in the record.

Finally, the result is shaped by the analysis population and crossover design. The registry reports 72 participants per dose group for the primary endpoint and defines the analyzed number as those with available CFA values. It does not explain all missing data handling, provide full ANCOVA details, or describe the intervention sequence and period handling. These limitations constrain how completely the primary estimate can be independently assessed.

18. Why This Trial Matters Statistically

This trial is statistically informative because it combines a randomized crossover design with a continuous primary endpoint and a model-based comparison. The endpoint is measured repeatedly across intervention periods, and the registry identifies ANCOVA as the reported method. That makes the distinction between a raw difference in group means and a model-based least-squares mean difference important: they are related summaries, but they need not be identical.

The estimates illustrate why a point estimate should not be interpreted without its uncertainty. The reported ANCOVA difference is positive, but its confidence interval includes zero and spans possible contrasts in both directions. The unadjusted recalculation also includes zero, and its interval is wider. Looking only at the positive point estimates would overstate what the data determine.

The record also demonstrates how design details affect statistical interpretation. Crossover studies can make efficient use of within-participant comparisons, but valid interpretation depends on how periods and participant-level relationships are handled. The registry does not report enough detail to evaluate those choices. Similarly, the CFA analysis count is smaller than overall enrollment, but the record does not fully explain participant flow or missing endpoint handling.

Finally, the trial lists multiple secondary outcomes alongside its primary endpoint. Without a reported multiplicity strategy, secondary results require more cautious interpretation. Together, the primary estimate, its interval, the crossover structure, and the reporting gaps show why statistical conclusions depend not only on a p-value but also on the design and analysis information available.

19. 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 leaves several trial-specific questions unresolved. It identifies a crossover model but does not report the treatment sequence, intervention-period order, or whether a washout period was used and, if so, its duration. These details can matter when assessing period effects or possible carryover. The record also does not specify how the ANCOVA handled the repeated measurements or whether it accounted for period or sequence.

The reported primary analysis includes 72 participants per dose group, compared with overall enrollment of 82. The registry defines the endpoint-specific N as participants with CFA values available, but does not provide a detailed flow of participants by period or explain why CFA values were unavailable. The missing-data method and any sensitivity analyses are not reported in the registry record.

The ANCOVA result is reported without covariates or a full model specification, so its adjustment cannot be reconstructed. The trial’s original sample-size rationale and design assumptions are not reported in the registry record. The planning illustrations based on the observed effect are not a substitute for those original assumptions.

Although several secondary outcomes are listed, the record does not provide numerical summaries for all of them in the information described. It also does not report a multiplicity procedure or a clinically important threshold for CFA. These reporting gaps limit assessment of the robustness, clinical relevance, and broader implications of the statistical findings. The limitations concern what can be evaluated from the registry information; they do not establish that particular methods were or were not used.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Randomized, Double-Blind, Dose Response-Control, Crossover Study to Evaluate the Safety and Efficacy of Two Doses of EUR-1008 (APT-1008) in Chronic Pancreatitis (CP) Participants With Exocrine Pancreatic Insufficiency (EPI) — NCT00788593.
• Registry record last updated 2014-03-12; status last verified 2014-01.
• Results first posted 2014-03-12.
• 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.

23. Record Summary

This Phase 3 randomized, triple-masked crossover study enrolled 82 participants with chronic pancreatitis and exocrine pancreatic insufficiency. Its primary objective was to compare percent CFA between high-dose and low-dose EUR-1008 (APT-1008) during hospital treatment in the first and second intervention periods.

The registry reports an ANCOVA least-squares mean difference of 1.023, with a 95% confidence interval from -0.656 to 2.701 and p = 0.228. An unadjusted recalculation from the posted summaries gives a mean difference of 0.99, with a 95% confidence interval from -2.526 to 4.506 and an unadjusted p-value of 0.581. Both intervals include zero, leaving uncertainty about the direction and size of the difference.

The record provides some secondary and safety information but does not report full details of the crossover analysis, missing-data handling, multiplicity procedures, or the original sample-size rationale.