Dose Finding Study in Colorectal Cancer Patients Receiving 5-FU-based Chemotherapy to Assess the Efficacy of Elsiglutide in the Prevention of Chemotherapy Induced Diarrhea (CID): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose Finding Study in Colorectal Cancer Patients Receiving 5-FU-based Chemotherapy to Assess the Efficacy of Elsiglutide in the Prevention of Chemotherapy Induced Diarrhea (CID) (NCT02383810), a randomized phase 2 study. The primary outcome is Proportion of Patients Experiencing a Maximum Grade ≥ 2 Diarrhea During the First Cycle of Chemotherapy in the Target Population.

2. Clinical Question

The study focused on chemotherapy-induced diarrhea during the first chemotherapy cycle. This endpoint captures whether a patient experienced at least the specified severity threshold at any point in that cycle, rather than measuring only a single day or the average severity across patients. The registry identifies the primary endpoint and its population, but the quantitative arm-level results are not reported in the registry record. Consequently, the size and precision of any difference between groups cannot be assessed from the registry information.

3. Trial Design

This was a phase II, randomized, stratified, parallel-group, placebo-controlled dose-finding study. The registry describes the study as quadruple-masked, while its brief summary calls it double-blind and double-dummy. It was conducted at multiple centres in multiple countries. Enrollment was 498 participants, and the status is completed.

Participants received one of four regimens: elsiglutide 10 mg, 20 mg, or 40 mg, or placebo. In the target population, treatment was given as a once-daily subcutaneous injection for 4 consecutive days starting on the day of chemotherapy administration. Each participant was to be followed through 3 consecutive chemotherapy cycles; the treatment period was specified for the first 2 cycles. The registry also describes an additional population receiving 5-FU-based chemotherapy with a monoclonal antibody. The primary endpoint evaluation excluded that additional population.

The primary efficacy question concerned the proportion of patients in the target population with a maximum Grade ≥ 2 diarrhea during Cycle 1, assessed by the Investigator. The stated timeframe is 15 days. The registry identifies the endpoint as a percentage of patients, but it does not provide the group-level percentages, comparative estimates, confidence intervals, or p-values in the record. Nor does it report the details of the stratification factors or explain how the randomization sequence was generated.

The study started in 2015-01 and reached primary completion in 2016-02. Those registry dates describe the recorded study timeline; they do not establish the timing of every participant’s treatment or follow-up. The registry record does not report a sample-size justification or enough detail to reconstruct the planned statistical analysis.

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.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS Target population, not including additional population

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: The full analysis set (FAS) was defined as all randomized patients who received at least 1 dose of study medication (elsiglutide or placebo) and (at least part of) the chemotherapy regimen in Cycle 1. The FAS Target set was defined as all patients from the Target population who were eligible for the FAS.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Patients Experiencing a Maximum Grade ≥ 2 Diarrhea During the First Cycle of Chemotherapy in the Target Population, measured over 15 days.

The primary endpoint is the proportion of patients in the target population who experienced a maximum Investigator-assessed diarrhea Grade ≥ 2 during the first chemotherapy cycle. It is a binary patient-level outcome: each patient is classified according to whether the severity threshold was reached during the stated assessment period, and the group result is expressed as a percentage of patients.

Using a maximum grade over a defined cycle captures whether a patient had a clinically notable episode at any point during that period. It is different from counting the total number of diarrhea events, measuring duration, or comparing average grades. The endpoint therefore answers a focused prevention question about the occurrence of diarrhea at or above a specified severity threshold in Cycle 1.

The endpoint description says that Investigator assessments for individual diarrhea events were missing for one patient who withdrew consent after 11 day in Cycle 1. For the primary endpoint, those data were imputed as Grade 0, in line with that patient’s eDiary data. The additional population was excluded from the primary endpoint evaluation. The registry does not report arm-level endpoint percentages or the statistical comparison results, so the outcome definition alone cannot establish the direction, magnitude, or precision of differences between treatment groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a proportion measure?

For a binary endpoint, each participant is classified into one of two outcome categories, such as experiencing or not experiencing the defined event. The group proportion is the number of participants classified with the event relative to the relevant analysis group. In this study, the event was a maximum Investigator-assessed diarrhea Grade ≥ 2 during Cycle 1. The registry gives the endpoint unit as percentage of patients, but does not report the arm-specific percentages or denominators for this efficacy outcome.

A proportion is a summary of how often an event occurred in a particular group. Comparing proportions addresses a different question from comparing counts of all episodes, because a participant with repeated episodes is still classified once for this endpoint. It also differs from comparing time to first event or the duration of symptoms. The endpoint’s exact definition therefore matters when interpreting any eventual estimate.

What would a confidence interval add?

A confidence interval describes uncertainty around an estimated effect under the assumptions of the analysis. It helps readers see which effect sizes are compatible with the observed data, rather than relying only on a single point estimate. In a trial with a binary outcome, uncertainty depends on the event information and the number of participants contributing to each group. The registry record does not report a confidence interval for the primary endpoint, so its precision cannot be assessed.

A confidence interval should be considered alongside the estimate and the clinical question. A range that includes effects in different directions may leave substantial uncertainty about the comparative result. A range concentrated around a relatively narrow set of values conveys greater precision. These are general interpretations; no such interval is available for the primary endpoint in the registry record.

Why do allocation and masking matter?

Random allocation is intended to make treatment groups comparable, on average, with respect to factors that could affect outcomes. Stratification can help balance selected factors across assigned groups, but the factors used for stratification are not reported in the registry record. Randomization does not guarantee identical groups, and it does not replace clear reporting of the analysis population and outcome results.

Masking can reduce the chance that knowledge of assigned treatment affects participant reporting, clinical assessment, or other aspects of care. The registry labels masking as quadruple and the study description also uses double-blind and double-dummy language. The registry record does not explain which roles were masked or give further operational detail. The primary outcome was assessed by the Investigator, making clarity about masking and assessment procedures relevant to understanding potential measurement bias.

How should a dose-finding comparison be read?

With three active doses and a placebo group, there are several possible comparisons: each active dose against placebo and the doses against one another. A pattern across doses may be informative for dose selection, but interpreting that pattern requires the actual estimates, their uncertainty, and the analysis plan. A larger observed estimate at one dose would not by itself prove a dose-response relationship. Chance variation and the number of comparisons also matter.

Multiplicity refers to the increased opportunity for apparently notable findings when several statistical tests are conducted. Methods for addressing it can include controlling an overall error rate or defining a hierarchy of comparisons. The registry record does not report how multiplicity was handled, so it is not possible to assess the inferential status of any dose-specific comparison. The primary outcome values and tests are also not reported in the record.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability is greater than a statistical model expects. It is a concern in some count-data analyses, where ignoring extra variability can make uncertainty appear too small. The primary endpoint in this study is a binary patient-level outcome rather than a count of repeated events, and the registry does not report an analysis model or over-dispersion assessment. It would be inappropriate to assume that a particular model or correction was used.

What is the role of a planning illustration?

A sample-size illustration based on an observed effect is a planning exercise, not a finding about what the completed trial achieved. Under the stated general assumptions, such an illustration can show how a hypothetical future design might be sized to detect a chosen fraction of an observed effect. It does not establish the probability that this completed trial detected an effect, and it is not observed power.

The registry record does not report the trial’s own sample-size justification. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Those assumptions are for an illustrative calculation and do not identify the original design rationale. No numerical planning values are included in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The study objective included comparing three elsiglutide doses with placebo and with one another. This creates several possible efficacy contrasts. When many tests are considered, the chance of at least one apparently notable result can increase. Statistical plans may address this through a prespecified testing sequence or another multiplicity adjustment. The approach used for this study is not reported in the registry record, so the strength of any potential dose-specific inference cannot be evaluated.

The primary endpoint description identifies the FAS Target population and states that the additional population was not included in the primary endpoint evaluation. It also notes one patient who withdrew consent after 11 day in Cycle 1 and whose missing Investigator assessments for individual diarrhea events were imputed as Grade 0, in line with the eDiary data. This is a specific imputation statement, not a complete account of missing data across the trial.

The registry record does not report the number of participants with missing endpoint data by arm, the full analysis-set rules, or sensitivity analyses exploring alternative assumptions for missing values. It also does not report whether the primary analysis used an intention-to-treat approach or another prespecified population definition beyond the stated FAS Target population label. These omissions limit assessment of how missingness and population selection might affect the result.

Because the primary arm-level results are not reported in the registry record, multiplicity and missing-data methods cannot be connected to observed estimates or their uncertainty. Any interpretation of the primary endpoint therefore remains limited to its definition and stated population.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: disease progression (1.6%), hypovolaemic shock (0.8%), death (0.8%), intestinal obstruction (0.8%), supraventricular tachycardia (0.8%).

The registry lists serious adverse event counts for each Overall set, with the number at risk and number affected, along with deaths. For elsiglutide 10 mg, 124 were at risk and 2 were affected by serious adverse events, with 1 death. For elsiglutide 20 mg, 125 were at risk and 4 were affected, with 1 death. For elsiglutide 40 mg, 123 were at risk and 3 were affected, with 2 deaths. For placebo, 125 were at risk and 6 were affected, with 3 deaths.

These are descriptive counts. The registry record does not state in this safety summary whether the serious events or deaths were judged related to study treatment, nor does it provide a comparative statistical analysis. Counts alone do not establish a treatment-related cause or allow a precise comparison of risk. The listed groups are Overall sets and should not be assumed to match the primary efficacy population.

The registry also lists serious adverse event terms, including Disease progression at 1.6%, and Hypovolaemic shock, Death, Intestinal obstruction, Supraventricular tachycardia, and Abdominal abscess at 0.8% each. These percentages are reported as listed; the denominator details and attribution criteria are not reported in the registry record. Safety counts and term listings should be interpreted as descriptions of reported events, not as evidence of causation.

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

The study addresses a clinically focused statistical question: whether the proportion of patients experiencing Investigator-assessed Grade ≥ 2 diarrhea during Cycle 1 differed across placebo and three elsiglutide dose groups in the target population. The randomized, placebo-controlled design is appropriate for comparing assigned groups, and the endpoint uses a defined severity threshold over a specified cycle.

However, the registry record does not report the primary outcome percentages or comparative estimates. It therefore does not show whether the event was more or less frequent in any group, how large any observed contrast was, or how uncertain that contrast may be. A conclusion about efficacy cannot be drawn from the design description or study objective alone. The missing result details also prevent assessment of whether findings were consistent across doses.

The endpoint captures whether a participant reached a severity threshold, not the total burden of diarrhea or every clinically relevant dimension of the experience. It does not, by itself, describe duration, recurrence, or severity distribution below and above the threshold. Those are distinct outcomes and should not be inferred from this primary measure.

The registry’s serious adverse event counts are also descriptive. They do not establish that an event was caused by a study treatment, and the record does not provide a formal safety comparison in the information. Nor should the enrollment figure be treated as the denominator for every efficacy or safety result: the primary endpoint excludes the additional population, and analysis-specific denominators are not reported.

In short, the available record identifies the trial design, treatment regimens, target population, and primary endpoint, but not the numerical primary efficacy findings. The evidence needed to judge the size, direction, and precision of the primary comparison is not reported in the registry record. This is a limit on interpretation of the registry record, not a conclusion about the treatment’s effect.

13. Why This Trial Matters Statistically

This trial is statistically notable as a dose-finding comparison with three active dose levels and a placebo group. Such a design can inform the selection of a dose for further study, but it also raises analytical questions about which comparisons are primary, how dose patterns are assessed, and how multiple testing is handled. The registry record states that doses were compared with placebo and with one another, while the specific inferential plan is not reported.

The primary outcome is a patient-level binary measure based on the maximum diarrhea grade during Cycle 1. That choice makes the endpoint comparatively direct to interpret: it concerns the proportion crossing a stated severity threshold, rather than a model-dependent average of repeated episode counts. At the same time, reducing a patient’s experience to whether the threshold was reached means the endpoint does not convey the full distribution of severity or duration.

The target population definition also matters. The primary evaluation excluded patients receiving 5-FU-based chemotherapy with a monoclonal antibody, even though the trial describes an additional population receiving such treatment. This distinction prevents the primary endpoint population from being casually equated with every participant described in the study.

The record gives a specific imputation for one patient with missing Investigator assessments and identifies the eDiary data as consistent with the Grade 0 imputation. This illustrates how a single missing-data decision can be documented, while also highlighting the importance of broader reporting on missingness and sensitivity analyses.

Finally, this case demonstrates that design details and a well-defined endpoint do not substitute for reported outcome estimates. Without the arm-level values and uncertainty measures, readers cannot judge the observed dose pattern or the precision of the primary result. Transparent reporting of those values and the analysis plan is essential for statistical interpretation.

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 principal limitation for interpreting efficacy is that arm-level primary endpoint results are not reported in the registry record. Percentages, comparative estimates, confidence intervals, and p-values are unavailable, so neither the direction nor precision of the primary comparison can be evaluated.

Further analysis details are not reported in the registry record, including the randomization strata, the statistical model, the handling of multiple dose comparisons, and a complete account of the primary analysis population. The record identifies the FAS Target population and one imputation decision, but does not report missing-data totals by group or sensitivity analyses. These gaps limit assessment of robustness.

The outcome timeframe is given as 15 days, and the primary endpoint is based on Investigator assessment during Cycle 1. The registry record does not provide additional detail about the assessment schedule or the operational rules for assigning maximum grades beyond the endpoint description. The additional population was excluded from the primary endpoint evaluation, so results from that population cannot be inferred from the primary endpoint definition.

Safety information is presented as group-level counts and listed terms. The registry record does not report attribution to treatment or a formal comparative safety analysis in the information. These counts should not be treated as causal estimates or as directly interchangeable with the target-population efficacy results.

The registry record also does not report the trial’s sample-size justification. Planning illustrations based on an observed effect are not a substitute for that rationale or for the completed trial’s outcome estimates. Collectively, these limitations mean the record supports a description of the study question and design, but not a quantitative conclusion about the primary treatment comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dose Finding Study in Colorectal Cancer Patients Receiving 5-FU-based Chemotherapy to Assess the Efficacy of Elsiglutide in the Prevention of Chemotherapy Induced Diarrhea (CID) — NCT02383810.
• Registry record last updated 2024-03-01; status last verified 2024-02.
• Results first posted 2024-03-01.
• 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

NCT02383810 is a completed phase II randomized, stratified, parallel-group, placebo-controlled dose-finding study sponsored by Helsinn Healthcare SA. It enrolled 498 participants with colorectal cancer receiving 5-FU-based chemotherapy. Participants were assigned to elsiglutide 10 mg, 20 mg, or 40 mg, or placebo; treatment was described as a once-daily subcutaneous injection for 4 consecutive days. The study started in 2015-01 and reached primary completion in 2016-02.

The primary endpoint was the proportion of patients in the target population with a maximum Investigator-assessed diarrhea Grade ≥ 2 during Cycle 1, within a 15 days timeframe. The additional population receiving chemotherapy with a monoclonal antibody was excluded from primary endpoint evaluation. The registry record describes an imputation of Grade 0 for one patient with missing Investigator assessments, in line with eDiary data.

Primary arm-level results and key analysis details are not reported in the registry record. Serious adverse event counts and deaths are listed by overall treatment group, but the record does not provide causal attribution in the safety summary.