Preliminary Efficacy and Safety Study of Oral Nepadutant in Infant Colic: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Preliminary Efficacy and Safety Study of Oral Nepadutant in Infant Colic (NCT01258153), a randomized phase 2 study. The primary outcome is Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline..

2. Clinical Question

3. Trial Design

This was a phase IIa, randomized, double-blind, placebo-controlled, parallel-group study of oral nepadutant in infantile colic. The registry lists quadruple masking. Its brief summary describes the study as multicentre and multinational and identifies three parallel groups: nepadutant low dose, nepadutant high dose, and matching placebo. The intervention summary specifies once-daily administration for seven days. The record does not give the dose amounts, allocation ratio, or further details of the randomization and masking procedures.

The study enrolled 115 participants and is marked completed. The recorded study start is 2010-11, and primary completion is listed as 2013-12. These registry dates describe the study record; they do not provide dates for individual assessments or explain the time between study milestones.

The primary outcome was the absolute change in mean daily crying and fussing time, in minutes, from baseline to the treatment assessment. The record describes baseline as starting at 6 pm on Day -4 and continuing until the first treatment administration. The treatment assessment used diary records collected for 72 hours, starting at 6 pm on Day 4. Secondary outcomes included responder status at the end of treatment, parental judgments at specified assessment points, and safety and tolerability measures. Numerical results for the primary outcome and the listed secondary outcomes are not reported in the registry record.

The registry lists six outcome measures and zero analyses. It does not report a statistical analysis plan, the planned primary comparison, or how results were to be adjusted for multiple outcomes. The sample-size assumptions associated with planning illustrations are not the trial's own design justification. The registry record does not report the trial's sample-size justification.

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

Analysis population for the primary outcome, as defined in the registry: 112 instead of 113, because 1 subject had no records at baseline and therefore the outcome could not be measured

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: 113 : ITT - defined as the safety population randomised with at least 24h diary recording post 1st dose of study treatment

6. Primary Endpoint

The registry lists the primary outcome as Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline., measured over Baseline and one week.

The primary endpoint measures change in mean daily time spent crying and fussing. The unit is minutes. The registry describes a baseline diary period beginning at 6 pm on Day -4 and ending at the first treatment administration, and an on-treatment diary period lasting 72 hours and beginning at 6 pm on Day 4. It characterizes the endpoint as an absolute change from baseline for the mean daily measure.

A diary-based measure can capture behavior across ordinary daily routines rather than relying only on a brief observation at a clinic visit. Repeated recording over consecutive days can also represent variation from day to day within the assessment period. These are general reasons why a trial might use a diary endpoint; the registry record does not state the rationale for choosing this measure or describe how diary entries were checked or summarized.

Change from baseline expresses the on-treatment measurement relative to each participant's baseline measurement. In general, this can help account for differences in starting levels, but interpretation depends on the analysis method and on how missing diary records are handled. Those details are not reported in the registry record. The endpoint is described as a mean, but numerical group means, changes, between-group estimates, and confidence intervals are not reported. Therefore, the endpoint definition alone does not show the direction, magnitude, or precision of the observed treatment comparisons.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a randomized, quadruple-masked, parallel-group study with two nepadutant dose groups and a matching-placebo group. The following explanations describe general statistical concepts; they do not identify methods used by this trial unless the registry explicitly reports them. The trial's detailed statistical analysis plan is not reported in the registry record.

What does the primary outcome represent?

The primary outcome is a continuous measure: mean daily crying and fussing time in minutes, expressed as an absolute change from baseline to the treatment assessment. A continuous endpoint can take a range of values rather than placing each participant in a simple event/no-event category. The meaning of a group comparison therefore depends on the estimated difference in changes, its uncertainty, and the direction used to define change. The registry record does not report those estimates or state how the direction of change was coded.

The endpoint is based on diary recording over specified periods. In general, an average can summarize repeated measurements, but the way diary entries are combined can affect the result. The registry describes the diary windows but does not report detailed scoring rules, requirements for completed diary entries, or the analysis model.

Why does randomization matter?

In general, random assignment aims to make treatment groups comparable at the start of a study, on average, so that differences in outcomes can be interpreted in relation to assigned treatment under appropriate study conduct and analysis. Randomization does not guarantee identical groups, especially in a trial with a finite number of participants. The registry identifies the allocation as randomized but does not report the sequence-generation method, concealment procedure, or allocation ratio.

Masking is intended, in general, to reduce the influence of treatment knowledge on participant behavior, outcome reporting, clinical care, or assessment. The record lists quadruple masking and describes the study as double-blind in its official title and brief summary. It does not identify the roles included in the masking designation or explain how masking was maintained.

How should estimates and uncertainty be read?

For a continuous outcome, an estimated group difference describes the contrast calculated under the chosen analysis. A confidence interval communicates uncertainty around that estimate: narrower intervals indicate greater precision under the method's assumptions, while wider intervals indicate less precision. A confidence interval does not establish that every value in its range is equally likely, and it does not by itself determine whether an effect is important to patients or caregivers. No primary-outcome estimate or confidence interval is reported in the registry record.

A p-value, when used, describes how unusual data at least as inconsistent with a specified null model would be if that model and the test assumptions held. It is not the probability that the null hypothesis is true and does not measure effect size. The registry record does not report a primary-outcome p-value or name the test used. The record therefore does not support claims of statistical significance or lack of significance for the primary endpoint.

What is over-dispersion, in general?

Over-dispersion occurs when observed variability is greater than a statistical model assumes. It can make standard errors too small and confidence intervals too narrow if the model does not account for the extra variability. This concept is relevant to some outcome distributions, such as counts, but the primary endpoint in this study is described as a continuous mean. The registry record does not report an over-dispersion assessment or a model that would allow one to determine whether it was relevant to the trial analysis.

What do planning assumptions mean?

The record describes sample-size planning illustrations based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions for illustrations, not evidence that the study used those assumptions in its original design. The record does not report the trial's own sample-size justification, and the illustrations are not observed power. Planning calculations ask how many participants might be needed under specified assumptions; they do not measure the probability that the completed trial has demonstrated an effect.

The registry's stated sample-size illustration method refers to participants per arm for most outcomes and to a total number of events for time-to-event outcomes. The primary outcome is described as continuous, but no numerical planning results are reported in the registry entries. No new sample-size estimate can be inferred from the design description alone.

What is not established by the registry record?

The record does not report the statistical model, covariates, handling of repeated measurements, missing-data method, analysis population definitions, multiplicity strategy, interim analyses, or prespecified contrast. Those details can affect estimates and uncertainty. Their absence means the endpoint description and trial design should not be mistaken for a complete account of the statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures. The primary outcome concerns change in mean daily crying and fussing time; secondary outcomes include responder status, parental judgments at specified time points, and safety and tolerability. Considering multiple outcomes or multiple comparisons can increase the chance of obtaining an apparently notable result by chance if each is assessed separately. General approaches to multiplicity include defining a hierarchy of hypotheses or adjusting decision thresholds, but the registry record does not report whether any approach was planned or used.

The record reports zero analyses and does not provide numerical estimates for the primary or secondary efficacy outcomes. It does not identify which contrasts were prespecified, whether analyses were adjusted, or whether any outcomes were omitted from the results record. A list of registered outcomes alone does not reveal the analysis plan or establish that every listed outcome was analyzed.

For the primary outcome, the record says the population was 112 instead of 113 because one subject had no baseline records and the outcome could not be measured. Since the endpoint is defined as change from baseline, a baseline value is needed to calculate that change. The record does not explain why the stated comparison is 112 instead of 113, how the figure relates to enrollment of 115, or how participants were distributed across analysis groups. It also does not report whether there were missing on-treatment diary entries or other missing data.

Analysis populations, such as an intention-to-treat or per-protocol population, are not reported in the registry record. Neither are imputation methods, sensitivity analyses, or rules for incomplete diaries. These omissions limit assessment of whether missingness could have affected the estimated treatment comparisons and whether the analysis preserved the benefits intended by randomization.

11. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchitis (2.6%).

The registry reports serious adverse events for the three groups as follows: zero participants in the nepadutant low-dose group, one in the nepadutant high-dose group, and zero in the placebo group. It separately reports other adverse events affecting 9 participants in the low-dose group, 6 in the high-dose group, and 5 in the placebo group. These are counts of participants affected, as represented in the registry record; they are not a complete account of the number, timing, duration, or severity of every event.

Bronchitis is listed among the top serious adverse-event terms at 2.6%. The registry record does not specify in this listing which group the term belongs to. Death counts are not reported in the registry record. No calculation of comparative rates or risk differences is made.

Adverse-event counts do not by themselves establish that an event was caused by treatment. They also do not show how exposure duration, event recurrence, or participant characteristics influenced the counts. The registry record does not report a detailed causal assessment or a comprehensive statistical comparison of safety outcomes. These figures should therefore be read as descriptive safety information, not as a definitive ranking of treatment safety.

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

The registry record establishes that a randomized, placebo-controlled, parallel-group study evaluated oral nepadutant at two doses in infants with infantile colic. It defines a primary outcome based on change in mean daily crying and fussing time and lists several secondary measures. It also reports enrollment, a note about the number with measurable primary outcomes, and selected adverse-event counts.

It does not report numerical primary-outcome results, group means, treatment contrasts, confidence intervals, or p-values. Thus, the registry record cannot quantify an observed difference in crying and fussing time, indicate its precision, or establish whether any difference was statistically significant. The absence of numerical outcome results is not evidence that groups had the same outcomes; it means the comparative efficacy result is not available in this record.

The record also does not give numerical results for the listed secondary efficacy measures. The adverse-event counts provide limited descriptive information but do not establish causality or a full comparative safety profile. No claim that nepadutant does or does not work, or that it is or is not safe, follows from the information.

More generally, a trial's design and endpoint definitions describe what investigators set out to compare, while outcome estimates describe what was observed. Interpretation of estimates also depends on their uncertainty, the analysis population, missing-data handling, and the prespecified statistical methods. Those elements are not reported in sufficient detail in the registry record. Accordingly, the record is useful for understanding the study question and basic design, but it does not support a quantified assessment of the primary treatment effect.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of how trial design and outcome reporting are distinct. The registry describes a randomized, masked comparison of two doses with matching placebo, and specifies a diary-based continuous primary outcome. Those details define the intended comparison and the measurement approach, but they cannot substitute for estimates of the observed outcomes.

The primary endpoint uses repeated diary recording over a baseline period and an on-treatment period. In general, that measurement structure raises analytic questions about how observations are summarized, how incomplete diaries are treated, and how participant-level change is compared across groups. The registry record does not answer those questions. Identifying the endpoint therefore helps clarify what an analysis would need to address, while also making clear why the analysis details matter.

The record's note that the primary measure was available for 112 instead of 113 participants because one subject had no baseline record illustrates a practical consequence of change outcomes: a baseline measurement is required to calculate change. The record does not reconcile those figures with enrollment of 115 or describe the resulting analysis populations. Transparent accounting of participants and missing observations is important for judging how closely the analyzed sample reflects the randomized groups.

Finally, the registry lists multiple outcomes but reports zero analyses and no numerical efficacy results. This makes multiplicity and analysis-plan questions impossible to evaluate from the record. Statistically, the key lesson is that design descriptions, outcome definitions, and adverse-event counts can provide context, but they do not establish the size, precision, or robustness of an efficacy finding. Those judgments require reported outcome estimates and sufficient methodological detail.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation for interpreting efficacy is that numerical results for the primary outcome are not reported in the registry record. There are no group estimates, between-group contrasts, confidence intervals, or p-values. Numerical results for the listed secondary outcomes are also not reported. This prevents assessment of effect magnitude, direction, precision, and consistency across outcomes.

The record does not report the nepadutant dose amounts, randomization ratio, detailed eligibility criteria, baseline participant characteristics, or the number analyzed in each group. It describes quadruple masking and also uses the term double-blind in the official title and brief summary, but does not explain which parties were masked or how masking was maintained. These limits constrain evaluation of the conduct and applicability of the study.

There is a discrepancy in the primary-outcome population note: it states 112 instead of 113 and attributes an unmeasurable outcome to one subject without baseline records. The registry does not reconcile this statement with total enrollment of 115 or describe the analysis population. Missing-data handling, diary completion requirements, and sensitivity analyses are not reported. These details are important for a change-from-baseline measure.

The record lists six outcomes and zero analyses but does not report the statistical model, planned contrasts, multiplicity approach, interim analyses, or the trial's sample-size justification. The sample-size assumptions described for planning illustrations are not the study's design justification and cannot provide observed power. Safety information is also limited: participant counts are reported for serious and other adverse events, but detailed event-level information and deaths counts are not reported in the registry record. These limitations mean the record is insufficient for a complete efficacy or safety appraisal.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Preliminary Efficacy and Safety Study of Oral Nepadutant in Infant Colic — NCT01258153.
• Registry record last updated 2015-06-10; status last verified 2015-05.
• Results first posted 2015-06-10.
• 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.

18. Record Summary

NCT01258153 is a completed phase IIa randomized, quadruple-masked, parallel-group study of oral nepadutant in infantile colic. The registry describes two nepadutant dose groups and matching placebo, with once-daily treatment for seven days. Enrollment was 115; the recorded start is 2010-11 and primary completion is 2013-12.

The primary outcome was absolute change in mean daily crying and fussing time, measured in minutes, from baseline to the on-treatment diary assessment. The registry lists six outcome measures and zero analyses. It notes that the primary outcome was measurable for 112 instead of 113 participants because one subject had no baseline records. Numerical efficacy results and the statistical analysis plan are not reported in the registry record.

Serious adverse events affected zero, one, and zero participants in the low-dose, high-dose, and placebo groups, respectively. Other adverse events affected 9, 6, and 5 participants in those groups. These counts are descriptive and do not constitute a full comparative safety analysis.