This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age (NCT01100606), a randomized phase 4 study. The primary outcome is Treatment Difference for Acceptability of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01100606 |
| Phase | Phase 4 |
| Condition | Cystic Fibrosis, Exocrine Pancreatic Insufficiency |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Forest Laboratories |
| Results posted | Yes |
2. Clinical Question
Population
Infants 1 to 12 months of age with exocrine pancreatic insufficiency associated with cystic fibrosis. The registry describes an intention-to-treat population of participants who received at least 1 dose and had partial or complete acceptability questionnaire data and clinical signs and symptoms of exocrine pancreatic insufficiency.
Intervention
EUR-1008 (APT-1008), identified in the registry as Zenpep, administered using one of two methods: in apple juice or in apple sauce. The study evaluated acceptability and safety of these modes of administration.
Comparator
The other administration method served as the comparison: EUR-1008 in apple juice versus EUR-1008 in apple sauce. The record describes a randomized crossover design, but does not report the treatment sequence, period details, or the precise statistical definition of the comparison.
Primary question
How did caregivers rate acceptability of the treatment methods, including ease and time of administration, infant acceptance, clarity of instructions, and satisfaction? The primary outcome is titled treatment difference for acceptability of treatment. Numerical results for that outcome are not reported in the registry record, so the relative acceptability of the methods cannot be determined from the posted results.
3. Trial Design
The registry describes a Phase 4, randomized, open-label, crossover study of EUR-1008 in infants 1 to 12 months of age with exocrine pancreatic insufficiency associated with cystic fibrosis. It lists enrollment as 15 and study status as completed. The listed start and primary completion dates are 2010-06 and 2010-12.
The two administration methods were EUR-1008 in apple juice and EUR-1008 in apple sauce. Because the study is described as a crossover, the design concerns participants receiving different methods at different points rather than a simple parallel-group comparison. The record does not report the sequence in which methods were given, how long each period lasted, whether there was a gap between periods, or how treatment period and sequence were handled in the analysis. Those details matter when interpreting a crossover comparison, but they cannot be inferred from the design label alone.
The study was open label, meaning masking was listed as none. Knowledge of the administration method could therefore influence caregiver ratings of ease, time, infant acceptance, and satisfaction. Randomization can help assign treatment order, but the record does not describe the randomization procedure or allocation concealment.
The registry identifies Forest Laboratories as the sponsor. Its brief summary also refers to Aptalis Pharma, formerly Eurand, as the sponsor. The posted record does not clarify the relationship between those sponsor references. Although the study is completed, the registry lists 0 analyses, and numerical results for the primary acceptability outcome are not reported. Completion status alone does not establish what results were collected or how they were analyzed.
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: All enrolled participants were administered Zenpep® 5,000 (pancrelipase) from open capsule mixed with a small amount of apple sauce in the screening period for 10 days.
First Treatment Period
| Stage | EUR-1008 (APT-1008) in Apple Juice First, Then in Apple Sauce | EUR-1008 (APT-1008) in Apple Sauce First, Then in Apple Juice |
|---|---|---|
| STARTED | 8 | 7 |
| COMPLETED | 8 | 7 |
| NOT COMPLETED | 0 | 0 |
Second Treatment Period
| Stage | EUR-1008 (APT-1008) in Apple Juice First, Then in Apple Sauce | EUR-1008 (APT-1008) in Apple Sauce First, Then in Apple Juice |
|---|---|---|
| STARTED | 8 | 7 |
| COMPLETED | 8 | 7 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Intention-to-treat (ITT) population included all participants who received at least 1 dose of study medication, had data (partial or complete) on acceptability questionnaire and clinical signs and symptoms of exocrine pancreatic insufficiency (EPI). Here, 'N' (number of participants analyzed) =participants who were evaluable for this measure.
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: Safety analysis population included all participants who received at least 1 dose of study medication.
| Characteristic | Unit | Entire Study Population |
|---|---|---|
| Participants analysed | 15 | |
| Age, Continuous | months | 5.7 (SD 3.15) |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 9 |
| Average Daily Number of Stools | average number of stools per day | 2.73 (SD 1.393) |
| Number of Stools Categorized as Per Consistency: Hard | average number of stools per day | 0.11 (SD 0.255) |
| Number of Stools Categorized as Per Consistency: Normal | average number of stools per day | 1.18 (SD 1.129) |
| Number of Stools Categorized as Per Consistency: Soft | average number of stools per day | 0.91 (SD 0.777) |
| Number of Stools Categorized as Per Consistency: Diarrhea | average number of stools per day | 0.48 (SD 0.801) |
| Number of Stools With Signs of Blood and Visible Oil or Grease: With blood | average number of stools per day | 0 (SD 0) |
| Number of Stools With Signs of Blood and Visible Oil or Grease: With visible oil or grease | average number of stools per day | 0.11 (SD 0.147) |
| Number of Abdominal Symptoms: Bloating: Mild Bloating | average number of bloating per day | 0.12 (SD 0.281) |
| Number of Abdominal Symptoms: Bloating: Moderate Bloating | average number of bloating per day | 0.04 (SD 0.101) |
| Number of Abdominal Symptoms: Bloating: Severe Bloating | average number of bloating per day | 0 (SD 0) |
| Number of Abdominal Symptoms: Flatulence: Mild Flatulence | average number of flatulence per day | 1.00 (SD 1.208) |
| Number of Abdominal Symptoms: Flatulence: Moderate Flatulence | average number of flatulence per day | 0.51 (SD 0.728) |
| Number of Abdominal Symptoms: Flatulence: Severe Flatulence | average number of flatulence per day | 0.03 (SD 0.099) |
| Number of Abdominal Pain Symptoms: Mild Abdominal Pain | average number of pain symptoms per day | 0.23 (SD 0.409) |
| Number of Abdominal Pain Symptoms: Moderate Abdominal Pain | average number of pain symptoms per day | 0.09 (SD 0.185) |
| Number of Abdominal Pain Symptoms: Severe Abdominal Pain | average number of pain symptoms per day | 0.02 (SD 0.066) |
6. Primary Endpoint
The registry lists the primary outcome as Treatment Difference for Acceptability of Treatment, measured over Baseline up to end of study (Day 21).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | units on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled treatment difference for acceptability of treatment. The registry describes an acceptability questionnaire with 9 questions. Q1-Q5 and Q7-Q9 used 5-point ratings; Q6 was not rated and asked for the name of the previous pancreatic enzyme product administered. The rated items addressed overall ease, time of administration, infant acceptance, clarity or completeness of instructions, overall satisfaction, and comparative ratings of ease, infant acceptance, and satisfaction.
The registry specifies a median and full range for the endpoint, with the timeframe from baseline up to the end of the study (Day 21). A median describes the middle of the observed ratings, while a full range describes their lowest and highest observed values. These summaries can convey the typical rating and its spread, but they do not show every response or quantify uncertainty around a treatment contrast.
Rating direction is not uniform across questions. Higher ratings indicate greater ease on Q1 and better comparative ratings on Q7-Q9, while higher ratings indicate longer administration time or greater difficulty for some other items. The question wording must therefore be considered when interpreting a score. The registry does not report the numerical ratings, the treatment difference, or how the separate questions were combined or compared.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study’s primary focus was acceptability of two ways of administering EUR-1008, not a comparison of different drugs. The registry describes a questionnaire covering practical administration, infant response, instructions, and satisfaction. This makes the endpoint relevant to how the administration methods were experienced by caregivers, but it does not itself establish a clinical effect on exocrine pancreatic insufficiency or cystic fibrosis.
Although the primary outcome is described as a treatment difference, the registry record does not report a median, range, treatment contrast, confidence interval, p-value, or other numerical result for that endpoint. It also does not state which rated items contributed to a single treatment-difference measure, if any. Consequently, the direction, size, and precision of any acceptability difference are not reported in the registry record. The absence of a numerical result is not evidence that the methods had equal ratings.
The registry lists secondary outcomes concerning daily stool counts; stool consistency; signs of blood and visible oil or grease; bloating, flatulence, and abdominal pain; abnormal clinical laboratory and vital signs findings; and abnormal oral mucosa findings. These outcome names indicate what the study intended to assess, but the record does not provide numerical findings for them. It lists 10 outcome measures and 0 analyses. No result about changes in these outcomes can therefore be drawn from the posted results.
The open-label design is important when reading acceptability ratings. Caregivers knew which administration method was being used, and ratings of ease, satisfaction, or infant acceptance may reflect that knowledge as well as the experience of giving the product. Randomization in a crossover study can help with assignment of treatment order, but the record does not describe the sequence or the statistical handling of treatment period, sequence, or possible carryover. It is not possible to assess those aspects of the analysis from the registry entry.
The posted safety entries list no serious adverse events in the named groups, while other adverse-event fields list affected participants. These entries should be read as descriptive registry counts, not as a complete comparative safety analysis. The registry record does not provide event definitions, severity detail for the other events, statistical comparisons, or an explanation of how crossover exposure is reflected in each group. Small study enrollment and the absence of reported outcome analyses further limit what can be concluded. Overall, the record documents a completed study and its intended questions, but provides too little numerical outcome information to estimate the acceptability or safety contrast between administration methods.
9. Statistical Methods Explained
The registry identifies randomization and a crossover model, but it does not report the statistical methods used to analyze the outcomes. The distinctions below explain the general statistical ideas relevant to this design; they should not be taken as a description of analyses that the investigators performed.
What does a crossover design compare?
In general, a crossover study exposes participants to more than one treatment or administration method in sequence. A comparison can then use information from the same participant under each method. This can reduce the influence of stable differences between participants, because those characteristics do not change between treatment periods. The design also makes treatment order and time important: responses can vary by period, and an earlier method could potentially affect a later observation. Appropriate analysis generally needs to account for the structure of repeated observations rather than treating every observation as unrelated.
For this study, the record identifies apple juice and apple sauce as the two methods and labels the model crossover. It does not report the sequence, period length, timing of outcome collection in each period, handling of incomplete sequences, or a model for the repeated observations. It also does not report whether period, sequence, or carryover effects were assessed. Without those details, readers cannot evaluate how the crossover structure was incorporated into an estimate of treatment difference.
What does the median and full range convey?
The primary outcome description specifies median and full range. As a general statistical summary, the median indicates the central ordered response, while the full range indicates the lowest and highest observed responses. This approach can be useful for rating data, which are ordered categories rather than measurements with guaranteed equal spacing between adjacent ratings. A median and range are descriptive summaries, however. They do not on their own provide a confidence interval for a treatment difference or a test of whether an observed contrast is compatible with chance variation.
The questionnaire’s rating direction varies among items. For example, a higher value on the ease item means greater ease, whereas the time item assigns higher values to longer administration time. Comparative items also have their own stated directions. General interpretation therefore requires attention to each question’s wording and response anchors. The record does not report a rule for combining item scores, a definition of the primary contrast, or the numerical results needed to interpret one.
How should a confidence interval be understood?
In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval for the same type of estimate. The registry record does not report a confidence interval for acceptability or for the listed secondary outcomes. The precision of any treatment difference cannot therefore be assessed from the posted results.
What do the planning assumptions mean?
The record describes sample-size planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The planning illustration considers detecting a stated fraction of the observed effect. These are planning assumptions, not evidence that the study had a particular probability of detecting an effect. The record does not provide a numerical observed effect for the primary endpoint, nor does it report the study’s own sample-size justification. Any planning illustration should be treated as hypothetical rather than as observed power or as proof that the study was adequately sized.
The planning description refers to equal allocation between two arms. That assumption does not by itself explain how a crossover design was planned or analyzed, and the registry does not report how the illustration was adapted to the crossover structure. No numerical planning results for this acceptability outcome are reported in the registry record.
Why can variability matter?
As a general point, highly variable responses make it harder to distinguish a systematic treatment contrast from random variation. For count outcomes, such as daily stool number, variability can exceed what a simple count model assumes; statistical methods may need to account for that over-dispersion. The record does not report the distribution of these outcomes or the models used, so it is not possible to determine whether over-dispersion was present or how it was addressed.
The registry’s analysis count is 0. It does not report a statistical analysis plan, model estimates, standard errors, hypothesis tests, confidence intervals, or adjustments to account for the crossover structure. General methods provide a framework for interpreting such information, but cannot fill in analyses that are not reported.
10. Multiplicity, Missing Data and Analysis Populations
The study lists multiple questionnaire items and several secondary outcomes. Testing or estimating many outcomes creates a multiplicity issue: when many comparisons are considered, some may appear notable by chance. As a general approach, investigators may define one primary comparison in advance, adjust for multiple testing, or treat secondary results as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among the questionnaire items, or which comparisons were prespecified for formal testing.
The primary description identifies an acceptability questionnaire with 9 questions, but Q6 was not rated; it asked for the name of the previous pancreatic enzyme product administered. The record does not explain whether the rated questions were analyzed separately or combined, or which ratings constituted the stated treatment difference. The secondary outcome list includes stool measures, abdominal symptoms, clinical laboratory and vital signs findings, and oral mucosa findings. Numerical analyses for these measures are not reported, and the registry lists 0 analyses.
The stated intention-to-treat population included participants who received at least 1 dose and had partial or complete acceptability questionnaire data and clinical signs and symptoms of exocrine pancreatic insufficiency. The record does not report the analyzed participant count; the population description ends with an incomplete statement about the meaning of N. It also does not explain how partial questionnaire responses were handled, how missing observations were treated, or whether participants missing data for particular outcomes were excluded from those analyses.
For a crossover study, incomplete treatment sequences or missing period-specific responses can affect which within-participant comparisons are available. That is a general concern, not a statement that such missingness occurred in this study. The registry does not report missing-data patterns or methods for addressing them. Without those details and the results, readers cannot assess how missing information or multiple outcomes affected the reported evidence.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Zenpep® | 0 | 15 | 0.0% |
| EUR-1008 (APT-1008) in Apple Juice | 0 | 12 | 0.0% |
| EUR-1008 (APT-1008) in Apple Sauce | 0 | 15 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Zenpep® | 11 of 15 |
| EUR-1008 (APT-1008) in Apple Juice | 10 of 12 |
| EUR-1008 (APT-1008) in Apple Sauce | 14 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Zenpep® | EUR-1008 (APT-1008) in Apple Juice | EUR-1008 (APT-1008) in Apple Sauce |
|---|---|---|---|---|
| Flatulence | Gastrointestinal disorders | 6 of 15 | 1 of 12 | 5 of 15 |
| Abdominal pain | Gastrointestinal disorders | 4 of 15 | 3 of 12 | 4 of 15 |
| Steatorrhoea | Gastrointestinal disorders | 3 of 15 | 2 of 12 | 4 of 15 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 2 of 12 | 6 of 15 |
| Abdominal distension | Gastrointestinal disorders | 2 of 15 | 3 of 12 | 2 of 15 |
| Diarrhoea | Gastrointestinal disorders | 3 of 15 | 2 of 12 | 1 of 15 |
| Pyrexia | General disorders | 1 of 15 | 2 of 12 | 3 of 15 |
| Teething | Gastrointestinal disorders | 2 of 15 | 1 of 12 | 1 of 15 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 1 of 12 | 1 of 15 |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 1 of 15 | 0 of 12 | 2 of 15 |
The registry lists serious adverse-event fields for Zenpep, EUR-1008 in apple juice, and EUR-1008 in apple sauce. Each listed group has 0 participants affected by serious events. The at-risk counts recorded for those entries are 15 for Zenpep, 12 for the apple-juice method, and 15 for the apple-sauce method. These are registry entries for the named groups; because the study is described as a crossover, the groups should not be assumed to represent separate sets of participants.
The other adverse-event fields list 11 affected participants in the Zenpep entry, 10 in the apple-juice entry, and 14 in the apple-sauce entry. These counts are descriptive and the record does not give event-level details, definitions, severity breakdowns, or a statistical comparison. They should not be treated as rates or as a direct estimate of relative safety.
No serious adverse-event terms are listed. Deaths are not reported in the registry record. A zero serious-event count in these entries does not establish that serious risks are absent, and differences in the other-event counts cannot be interpreted without more detail about exposure, overlap, and event ascertainment.
12. What the Result Does, and Does Not, Mean
The study addressed a practical question: how caregivers rated two ways of administering EUR-1008 to infants with cystic-fibrosis-associated exocrine pancreatic insufficiency. Its questionnaire covered ease, time, infant acceptance, instructions, and satisfaction. The crossover design was intended to compare administration methods within a randomized study, and the registry describes safety and clinical signs and symptoms as additional areas of interest.
The record does not report numerical results for the primary treatment difference or for the listed secondary outcomes. It therefore does not show whether one method received more favorable ratings, how large any difference was, or how precise an estimate might be. This lack of results should not be interpreted as a finding of no difference. The 0 analyses listed in the registry also mean there are no posted statistical analyses from which to draw an estimate or test result.
The study’s acceptability measure is not the same as a direct measure of clinical effectiveness. Caregiver ratings can address whether a method is manageable or acceptable, but they do not establish the effect of the product on the underlying condition. Likewise, the names of secondary outcomes indicate what was assessed, not what happened to those outcomes.
The safety entries record 0 serious events in each named group and other-event counts, but they do not provide a full comparative safety analysis. The record does not report deaths, and it does not provide enough event detail to characterize the nature or severity of the other events. These limitations preclude strong conclusions from the posted counts.
Accordingly, the registry record establishes the design, population, intended outcomes, and some adverse-event counts, but it does not provide the outcome results needed to judge the comparative acceptability of apple juice and apple sauce. A completed study status does not substitute for numerical outcome reporting. Interpretation should remain limited to what is recorded rather than filling in missing estimates or analysis details.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how a design can be aimed at a practical, caregiver-reported question rather than only a clinical laboratory or symptom outcome. The primary questionnaire addressed several aspects of administration, and the crossover model could, in general, allow comparisons that account for stable differences between participants. Those features make clear reporting of treatment sequence, periods, and repeated-measure analysis especially important.
The registry record illustrates the difference between an outcome being named and its result being available. It specifies a median and full range for the primary acceptability endpoint and lists a range of secondary outcomes, but reports 0 analyses and no numerical endpoint estimates. Without results, readers cannot assess either the direction or precision of the intended comparison. This is a reporting limitation, not evidence that the study found no effect or no difference.
It also highlights the importance of defining questionnaire outcomes. The items use different rating anchors and directions, and one question is not rated. A report that states how item-level answers were summarized and how the overall treatment difference was defined would help readers understand what the endpoint represents. Statistical interpretation depends on those definitions as much as on the choice of a summary measure.
Finally, a crossover design calls for transparent reporting of sequence, period, missing observations, and the handling of within-participant data. Those details are not reported in the registry record. For researchers and clinicians reading registry entries, separating design information from outcome evidence is essential: a well-described question is not itself an answer to that question.
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 registry record offers limited information for interpreting this specific study. It identifies a randomized, open-label crossover design but does not report treatment order, period duration, how outcomes were timed within periods, or how the crossover structure was analyzed. Without these details, it is not possible to assess period effects, sequence effects, or possible carryover as handled in the analysis.
The primary endpoint is described as a treatment difference for acceptability, with median and full range as the summary. The record does not provide the actual values, an estimate of the treatment contrast, a confidence interval, or a p-value. It also does not explain whether the rated questionnaire items were evaluated individually or combined, or how the opposite directions of some response scales were addressed. The primary population description is incomplete where it begins to define N, and the analyzed participant count is not reported.
The open-label design may matter for subjective caregiver ratings because the administration method was not masked. The registry does not describe steps to reduce or assess potential influence of treatment awareness. It also does not report the statistical analysis plan, multiplicity handling, or missing-data methods. Although the record names 10 outcome measures, it lists 0 analyses and does not provide numerical secondary-outcome findings.
Safety information is also limited. The record lists serious-event counts and other adverse-event counts but does not give event-level descriptions or explain how the crossover exposure is reflected in group entries. Deaths are not reported in the registry record. These limitations restrict interpretation of both the acceptability comparison and the safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Mode of Administration and Safety of EUR-1008 (APT-1008) in Infants 1 to 12 Months of Age — NCT01100606.
- Registry record last updated 2014-04-10; status last verified 2014-03.
- Results first posted 2014-04-10.
- 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.
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18. Record Summary
The registry describes a completed Phase 4, randomized, open-label crossover study of EUR-1008 in infants 1 to 12 months of age with exocrine pancreatic insufficiency associated with cystic fibrosis. Enrollment is listed as 15. The two administration methods were EUR-1008 in apple juice and EUR-1008 in apple sauce.
The primary outcome was treatment difference for acceptability, assessed with a questionnaire covering administration and infant acceptance. The record lists secondary stool, abdominal symptom, laboratory, vital signs, and oral mucosa outcomes. It reports 0 analyses and does not give numerical primary or secondary results. Serious adverse-event counts are listed as 0 in each named group; other adverse-event fields list affected participants. The registry does not report deaths.