Efficacy and Safety Study of Creon IR in Subjects With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of Creon IR in Subjects With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis (NCT02415959), a randomized phase 2 study. The primary outcome is Coefficient of Fat Absorption (CFA).

2. Clinical Question

3. Trial Design

This was a Phase II, multicenter, randomized, parallel-group, active-controlled, double-blind dose-ranging study. The registry record identifies masking as triple. It records the study as completed, with enrollment of 70. Abbott is listed as the sponsor. The study concerned pancreatic exocrine insufficiency in subjects with cystic fibrosis.

Participants were assigned to one of five groups: four Creon IR dose regimens and one Creon DR/GR comparator regimen. All regimens were given five times daily, during 3 meals and 2 snacks, for 6 to 7 days. The Creon IR groups were described using different daily lipase doses per gram of fat and different target total daily doses. The DR/GR comparator was listed at 4,000 Ph. Eur. U lipase/g fat/day, with a target total daily dose of 400,000 lipase units.

The primary outcome was measured at the end of the double-blind treatment period. Posted group summaries include 13 participants for the low-dose group, 13 for medium dose, 14 for high dose, 13 for maximum dose, and 13 for DR/GR. The Full Analysis set excluded four randomized subjects for lack of post-baseline efficacy data, including two subjects whose stools were mixed up at the analytical laboratory. The registry record does not report further details about sequence generation, allocation concealment, or the exact masking procedures.

The study also recorded Coefficient of Nitrogen Absorption, Stool Fat Content, and Stool Weight as secondary outcomes. Although the record lists five outcome measures, it posts results for three secondary endpoints. The original statistical plan and the trial's own sample-size justification are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis set. Four randomized subjects excluded because no post-baseline efficacy data (two non-completers and two subjects whose stools were mixed-up with each other at the analytical laboratory).

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.

6. Primary Endpoint

The registry lists the primary outcome as Coefficient of Fat Absorption (CFA), measured over End of the 6 to 7 days double-blind treatment period.

The primary endpoint was the Coefficient of Fat Absorption (CFA), reported as a percentage of fat intake. It was measured at the end of the 6 to 7 days double-blind treatment period. The registry record defines CFA using fat intake and fat excretion: CFA (%) = 100 [fat intake - fat excretion] / fat intake. In general, an absorption coefficient expresses how much of an ingested substance is absorbed rather than excreted. CFA therefore condenses information about both recorded intake and stool fat excretion into one continuous measure.

The endpoint is relevant to this study because pancreatic exocrine insufficiency concerns digestion and absorption, and the trial's stated objective was to assess the efficacy and safety of different Creon IR doses against Creon DR/GR. It provides a quantitative outcome that can be summarized by a mean and standard deviation for each group. Such summaries describe the group average and the spread of individual measurements; they do not show the full distribution or individual participant trajectories.

The primary analysis population was the Full Analysis set. Four randomized subjects were excluded because they had no post-baseline efficacy data, with two non-completers and two cases of stools mixed up with each other at the analytical laboratory. This missing-data context matters when interpreting group summaries: they describe participants included in the endpoint analysis, not necessarily every randomized subject.

7. Results Posted in the Registry

• Creon IR Medium Dose: mean 70.90 versus 71.00 on control; difference -0.10 (95% CI -10.23 to 10.03), standardized effect d = -0.01; z-test p = 0.985.
• Creon IR High Dose: mean 71.80 versus 71.00 on control; difference 0.80 (95% CI -9.63 to 11.23), standardized effect d = 0.06; z-test p = 0.881.
• Creon IR Maximum Dose: mean 75.90 versus 71.00 on control; difference 4.90 (95% CI -3.49 to 13.29), standardized effect d = 0.45; z-test p = 0.253.
• Creon® (DR/GR): mean 92.30 versus 71.00 on control; difference 21.30 (95% CI 14.27 to 28.33), standardized effect d = 2.33; z-test p = <0.001.

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.

Coefficient of Nitrogen Absorption (CNA)

• 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:
  • Creon IR Medium Dose: mean 73.20 versus 71.00 on control; difference 2.20 (95% CI -4.25 to 8.65), standardized effect d = 0.26; z-test p = 0.504.
  • Creon IR High Dose: mean 76.20 versus 71.00 on control; difference 5.20 (95% CI -1.70 to 12.10), standardized effect d = 0.57; z-test p = 0.139.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Creon IR Medium Dose and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Creon IR High Dose and the control. The interval gives the range of effects that remain compatible with the data.

Stool Fat Content

• 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:
  • Creon IR Medium Dose: mean 87.10 versus 87.50 on control; difference -0.40 (95% CI -30.60 to 29.80), standardized effect d = -0.01; z-test p = 0.979.
  • Creon IR High Dose: mean 84.10 versus 87.50 on control; difference -3.40 (95% CI -34.52 to 27.72), standardized effect d = -0.08; z-test p = 0.830.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Creon IR Medium Dose and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Creon IR High Dose and the control. The interval gives the range of effects that remain compatible with the data.

Stool Weight

• 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:
  • Creon IR Medium Dose: mean 905.30 versus 889.00 on control; difference 16.30 (95% CI -185.27 to 217.87), standardized effect d = 0.06; z-test p = 0.874.
  • Creon IR High Dose: mean 793.80 versus 889.00 on control; difference -95.20 (95% CI -312.13 to 121.73), standardized effect d = -0.33; z-test p = 0.390.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Creon IR Medium Dose and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Creon IR High Dose and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes cover related but distinct aspects of digestion and excretion: Coefficient of Nitrogen Absorption, Stool Fat Content, and Stool Weight. Across these measures, the general descriptive pattern is that group means are not identical across regimens, and the DR/GR group occupies a different part of the observed pattern from the IR groups. These endpoints add context to the primary CFA outcome, but they do not replace it or independently confirm a single treatment conclusion.

CNA is another absorption coefficient, while stool fat content and stool weight quantify material measured in stool over the stated period. In general, related endpoints can provide complementary information, but they may differ in variability, measurement properties, and sensitivity to individual observations. Agreement across measures can be informative; disagreement can also reflect that the measures capture different aspects of the study. The posted secondary summaries should therefore be read as separate outcomes, not combined into a single unreported score.

The registry record lists secondary results but no reported analyses. The recalculated comparisons available for some secondary endpoints are unadjusted and not a complete sponsor analysis. Because multiple outcomes and dose comparisons create multiple opportunities to observe an apparently notable result by chance, unadjusted secondary findings carry less inferential weight. No multiplicity adjustment is reported, and the secondary outcomes should be treated as exploratory descriptions rather than as independent confirmatory evidence.

The primary and secondary measures were assessed at the end of the same short double-blind treatment period. They describe outcomes over that period and do not address longer-term patterns. The secondary endpoints help place the primary measure in context, but the registry record does not report a prespecified hierarchy or analysis plan explaining how they were intended to influence interpretation.

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

• Coefficient of Nitrogen Absorption (CNA)
• Stool Fat Content
• Stool Weight

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant's CFA is expressed as a percentage of fat intake. The posted group statistic is the mean, and dispersion is reported as the standard deviation. In general, a mean describes the central value of observations, while a standard deviation describes how spread out observations are around that mean. Neither statistic alone reveals skewness, outliers, or the shape of the observations.

What do the comparisons represent?

The comparison estimates are unadjusted mean differences, using the low-dose group as the reference. A mean difference is the value in the compared group minus the value in the reference group. Positive estimates indicate a higher observed group mean than the low-dose mean; negative estimates indicate a lower observed group mean. These are unadjusted recalculations from the posted group summaries, rather than sponsor-reported model results. The registry record lists no reported analyses for the primary outcome.

Each confidence interval gives a range of values compatible with the observed data under the calculation's assumptions. In general, a confidence interval reflects sampling uncertainty, not the range in which most individual participants' values lie. A wide interval means the estimate is imprecise; an interval that includes zero indicates that the data are compatible with no mean difference as well as with differences in either direction. P-values are also unadjusted and should not be read as measures of effect size or importance.

Why do standard deviations matter?

Between-person variability affects the precision of a mean comparison. Greater spread generally makes it harder to estimate a group mean precisely when the number of observations is held constant. The group standard deviations differ across arms, so the observed mean difference should be read with its interval rather than in isolation. The DR/GR group has a notably smaller reported standard deviation than the IR groups, while the IR group values show wider spread.

The posted recalculation uses the group means, standard deviations, and analysis counts to estimate differences and confidence intervals. The comparison details also include pooled standard deviations and standardized effect estimates. A standardized effect expresses a mean difference relative to a pooled measure of variability, allowing effects on a common scale. This can help describe magnitude across outcomes with different units, but it does not replace the original-unit difference or determine clinical importance. In general, standardization is sensitive to the variability in the analyzed groups.

What can the p-values establish?

A p-value describes how unusual data at least as incompatible with a null hypothesis would be under that hypothesis and the calculation's assumptions. It does not give the probability that the null hypothesis is true, nor does it measure the probability that a result will replicate. The reported p-values are unadjusted; no correction for testing several dose comparisons or outcomes has been applied in these recalculations. Consequently, they should be interpreted with the confidence intervals and the multiplicity context, not as a stand-alone ranking of treatments.

The comparison calculations are based on posted summary statistics and a conventional unadjusted two-group comparison. They are not substitutes for the sponsor's own analysis. The registry record does not report a statistical analysis plan, adjustment variables, a model specification, a missing-data method, or a prespecified multiplicity procedure. It also does not report whether any interim analyses took place. Those details cannot be inferred from the numerical summaries.

How should missing outcome data be considered?

The Full Analysis set excluded four randomized subjects for lack of post-baseline efficacy data. Two were non-completers, and two had stool samples mixed up at the analytical laboratory. In general, excluding participants with no outcome data means the available-case group summaries may differ from the results that would have been obtained under another missing-data approach. The registry record does not report imputation, sensitivity analyses, or further information about the missing outcomes. The laboratory mix-up is a specific data-quality issue; the record does not describe any additional correction or review beyond the stated exclusions.

These methods describe what can be understood from the posted summaries. They do not establish that the recalculated comparisons match the original protocol's primary analysis. The record's analysis population and outcome definitions are available, but the original inferential plan and sponsor analysis results are not reported in the registry record.

11. Confidence Intervals and Precision

Precision concerns how narrowly the observed data locate an estimated group difference. For CFA, the interval for medium dose versus low dose extends from -10.23 to 10.03 around an estimate of -0.1. The high-dose interval extends from -9.632 to 11.23 around 0.8. The maximum-dose interval extends from -3.493 to 13.29 around 4.9. Each of these intervals includes zero and also permits differences in either direction. The posted data therefore leave substantial uncertainty about the corresponding IR-versus-low-dose mean differences.

The DR/GR comparison estimate is 21.3, with an interval from 14.27 to 28.33. This interval does not include zero and is narrower than several IR comparison intervals. It describes uncertainty in the estimated mean difference under the unadjusted recalculation; it is not an interval for individual CFA values and does not remove the limitations of the analysis population or short treatment period.

Precision is influenced by both variability and the amount of observed data. Each primary group summary is based on 13 or 14 participants, and the posted standard deviations vary across groups. A confidence interval is thus essential context: the point estimate alone can make a result seem more exact than the available data support. Conversely, an interval including zero does not prove equivalence or rule out differences that may matter; an equivalence conclusion would require prespecified margins and an appropriate analysis, which are not reported in the registry record.

These are unadjusted recalculated intervals based on summary statistics, not sponsor-reported intervals. Their interpretation should remain tied to that calculation and its assumptions.

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.

Read each planning row as an illustration of the participants per arm that a hypothetical two-arm study would need to target a specified fraction of an observed effect. The listed figures are participants per arm, not total participants or total events. The 80% power column means the hypothetical design would have an 80% chance of detecting the specified effect at the stated significance level, under the planning assumptions. The 90% column represents a higher chance of detection under the same assumptions and therefore generally requires more participants.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is the stated fraction of the observed effect. Rows for 100%, 75%, and 50% of the observed effect illustrate how the required per-arm count changes as the target effect becomes smaller. Smaller effects need more participants because they are harder to distinguish from random variation. In some comparisons, the observed effect is close to zero, so the resulting planning figures become extremely large; these are mathematical illustrations based on that observed estimate, not realistic design recommendations.

The planning figures are not observed power. They do not describe the probability that this completed trial detected an effect, and they are not the original trial's design calculations. The trial's own sample-size justification and original planning assumptions are not reported in the registry record. The curve should be interpreted as the same planning relationship across candidate effects and sample sizes, not as additional evidence about treatment outcomes.

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 = -0.100; pooled standard deviation σ = 13.171.
2. n = 2 × (1.96 + 0.842)² × 13.171² / -0.100² = 272,332.6, rounded up to 272,333 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 <- -0.0999999999999943                      # observed difference in means
sigma <- 13.1713704677987                     # 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(2415959)
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 = 272,333 (80% power), 364,577 (90% power)
 75% of observed effect: n per arm = 484,147 (80% power), 648,136 (90% power)
 50% of observed effect: n per arm = 1,089,331 (80% power), 1,458,305 (90% power)
power.t.test: 272333.5 
Simulated power at n = 272,333 per arm: 0.798 (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. Multiplicity, Missing Data and Analysis Populations

The trial includes four Creon IR dose groups and an active comparator, as well as a primary endpoint and several secondary endpoints. Comparing several groups and outcomes creates a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result can rise. The posted comparison p-values are unadjusted. The registry record does not report a multiplicity strategy, such as a prespecified testing sequence or correction, so the results should not be interpreted as if such adjustment had been applied.

The record identifies the CFA primary outcome and the Full Analysis set, but the original statistical analysis plan is not reported in the registry record. The number and specification of sponsor analyses are not reported, and no reported analyses are listed for the outcomes in these summaries. The posted pairwise comparisons are recalculations from summary statistics, not a substitute for the original analysis plan. Adjustment for baseline characteristics, stratification factors, or other covariates is not reported in the registry record.

Missing post-baseline efficacy data led to exclusion of four randomized subjects from the Full Analysis set. The record explains that two were non-completers and two had stools mixed up with each other at the analytical laboratory. It does not report imputation, sensitivity analyses, or a comparison of included and excluded participants. In general, available-case summaries can be affected if people with missing outcomes differ systematically from those with observed outcomes; whether that occurred cannot be determined from the registry record.

The registry record does not report interim analyses, stopping rules, or how the original sample size was justified. These absent details limit assessment of whether the reported comparisons correspond to prespecified decisions or whether the analysis approach changed. They should be treated as unreported rather than assumed absent from the conduct of the study.

15. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infective pulmonary exacerbation due to cf (7.1%).

The adverse-event summaries list 14 participants at risk in each group. Serious adverse events affected 0 participants in the low-dose, medium-dose, maximum-dose, and DR/GR groups, and 1 participant in the high-dose group. The registry record lists infective pulmonary exacerbation due to CF as a top serious event term at 7.1%. These figures describe the posted safety summaries and do not establish that an event was caused by a study regimen.

Other adverse events affected 10 participants in the low-dose group, 9 in medium dose, 7 in high dose, 9 in maximum dose, and 7 in the DR/GR group. The registry record does not report death counts; deaths are not reported in the registry record. Serious adverse events and other adverse events are distinct categories, and the counts should not be added together because the record does not clarify participant overlap between categories.

These observations come from groups followed during a 6 to 7 days treatment period. The summaries do not provide event-level detail, timing, duration, severity grading beyond the serious classification, or exposure-adjusted rates. The small group sizes and short observation period limit what can be inferred about uncommon or later events.

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

The posted results describe group averages and variability in CFA at the end of a short treatment period for participants with cystic-fibrosis-related pancreatic exocrine insufficiency. The observed mean was higher in the DR/GR group than in the low-dose group, while the means for the IR groups were closer to the low-dose mean. The unadjusted comparison intervals indicate that the IR-versus-low-dose estimates are imprecise, while the DR/GR-versus-low-dose interval is entirely above zero. These are statements about the posted data and recalculated comparisons.

They do not establish how the regimens would compare in a broader population, over a longer period, or under a different analysis population. The Full Analysis set excluded four randomized subjects, including two with no post-baseline data and two affected by a laboratory stool mix-up. The record does not report sensitivity analyses to assess how those exclusions might influence the results.

A statistically notable comparison is not necessarily a measure of clinical importance. The registry record does not provide a threshold for a clinically meaningful CFA difference, so the numerical difference cannot be classified against such a threshold. Likewise, a confidence interval that includes zero does not prove that two regimens are equivalent. Equivalence or non-inferiority would require a prespecified margin and a suitable analysis, neither of which is reported in the registry record.

The study's dose-ranging design and posted endpoints permit descriptive comparison of several regimens, but they do not by themselves establish a dose-response relationship. The original statistical plan, multiplicity handling, and sponsor analyses are not reported. Secondary outcomes provide additional descriptive measures but are also subject to multiplicity and should not be treated as confirmatory results without the intended analysis framework.

Safety summaries record serious and other adverse events during the study, but the brief observation period and group sizes limit their ability to characterize uncommon or long-term events. Overall, the registry record offers a short-term snapshot of measured outcomes and safety counts, with uncertainty and reporting gaps that should remain part of any interpretation.

17. Why This Trial Matters Statistically

This trial is statistically useful as an example of the distinction between a dose-ranging design and a definitive estimate for each possible comparison. Several dose groups create a broad descriptive picture, but the small number of observations in each group leaves uncertainty around many mean differences. The group means alone would not communicate that uncertainty; the confidence intervals show how much the estimated comparisons can vary under the recalculation.

The outcome also illustrates why measurement definition matters. CFA is calculated from fat intake and fat excretion, then summarized as a continuous group measure. Its interpretation depends on the quality and completeness of both inputs. The exclusion of two subjects because of a stool mix-up at the analytical laboratory is a concrete example of how data handling can affect the available analysis population, apart from participant completion.

The record also supports a useful distinction between registry outcome summaries and the original statistical analysis. The posted comparisons are unadjusted recalculations from means and standard deviations, while sponsor analyses and the original analysis plan are not reported. Readers can inspect effect estimates and intervals, but cannot establish how those compare with prespecified models, multiplicity procedures, or sample-size assumptions.

Finally, the secondary endpoints and safety summaries broaden the descriptive account but do not remove uncertainty in the primary result. Treating unadjusted secondary findings as exploratory and keeping the short observation period in view helps avoid overstating what this Phase II study can establish. Its statistical importance lies in making the relationship between design, measurement, precision, and reporting limitations visible.

18. 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 primary endpoint summaries come from modest-sized groups, with 13 or 14 participants contributing to each group mean. As a result, estimates may be sensitive to individual observations. The standard deviations differ among groups, and the registry record provides summaries rather than participant-level data or distribution plots, limiting assessment of outliers, skew, or other distributional features.

The analysis population excluded four randomized subjects for no post-baseline efficacy data. The record gives the reasons but does not report imputation or sensitivity analyses. The laboratory mix-up involving two subjects is a specific data-integrity concern; the registry record does not describe further investigation or the potential impact of the mix-up beyond excluding those subjects.

The double-blind treatment period lasted 6 to 7 days, so the posted outcomes and adverse-event summaries address a short interval. They do not characterize longer-term outcomes. Safety counts are not accompanied by detailed event-level descriptions, and deaths are not reported in the registry record.

The registry record does not report the original statistical analysis plan, sample-size justification, adjustment strategy, or multiplicity procedure. The available pairwise comparisons are unadjusted recalculations, and no sponsor analyses are posted for the endpoints. These gaps limit evaluation of prespecification and prevent direct comparison with a sponsor's inferential analysis.

Finally, the reported secondary results are not accompanied by a stated hierarchy or confirmatory testing plan. They can describe related outcomes but cannot resolve limitations in the primary analysis. The record does not report a clinically meaningful CFA threshold, so statistical differences cannot be translated into a threshold-based judgment of importance.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of Creon IR in Subjects With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis — NCT02415959.
• Registry record last updated 2016-04-04; status last verified 2016-03.
• Results first posted 2016-02-17.
• 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.

22. Record Summary

NCT02415959 is a completed Phase II randomized, multicenter, parallel-group, active-controlled, double-blind dose-ranging study sponsored by Abbott. It enrolled 70 participants with pancreatic exocrine insufficiency due to cystic fibrosis and compared four Creon IR regimens with Creon DR/GR.

The primary endpoint was CFA at the end of the 6 to 7 days double-blind treatment period. The registry record reports group means and standard deviations for the Full Analysis set, which excluded four randomized subjects without post-baseline efficacy data. Secondary results cover CNA, Stool Fat Content, and Stool Weight. Safety summaries report serious and other adverse events; deaths are not reported in the registry record.

Pairwise estimates and confidence intervals described in the statistical interpretation are unadjusted recalculations from posted summary statistics. The original analysis plan, multiplicity approach, and sample-size justification are not reported in the registry record.