Safety and Tolerability Extension Trial for Patients With Chronic Idiopathic Constipation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability Extension Trial for Patients With Chronic Idiopathic Constipation (NCT01895543), a na phase 3 study. The primary outcome is Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

The record therefore addresses safety and tolerability in patients followed during an extension period. Investigators recorded AEs from informed consent through the last visit, with information collected at each visit and events entered in an AE log for each patient. This describes the collection period and process, but does not provide details about event-specific monitoring rules or how investigators judged whether an event was related to treatment.

Other outcomes listed include use of over-the-counter laxatives, global evaluations of constipation severity and treatment effectiveness, quality of life, and health-status measures. Those outcomes could describe symptom experience and patient-reported status, but their numerical results are not reported in the registry record. The posted primary question is limited to counts of patients with AEs and SAEs. Without a concurrent control group, the counts describe events observed among treated participants; by themselves, they cannot establish how those counts compare with what would have occurred under another treatment or no treatment.

3. Trial Design

This is a Phase 3, multicenter, open-label safety and tolerability extension trial for patients with chronic idiopathic constipation. The trial is marked completed. Its recorded start was 2013-09 and its primary completion was 2015-05. Total enrollment is 411. The official title describes daily elobixibat at 5 mg and 10 mg, while the intervention and arm details list elobixibat 10 mg only. The 5 mg arm details are not reported in the registry record.

The design is identified as single group, with masking recorded as none and allocation as NA. These features mean that the posted results do not describe a randomized, blinded comparison between treatment arms. The adverse-event result instead reports counts for the EBX 10 group, with 409 patients at risk for both serious and other adverse events. The record identifies the Safety Analysis Set as the primary outcome population. It does not explain the difference between total enrollment and the safety-set denominator.

The primary outcome covers the overall 52-week treatment period. Investigators recorded AEs from informed consent through the last visit, identified as Visit 6, and collected information at each visit. The registry record does not detail the visit schedule, treatment exposure for each participant, the handling of patients who stopped treatment early, or the event coding procedures.

Several secondary outcomes are named, covering laxative use, global assessments, PAC-QOL, EQ-5D-5L, and EQ-VAS. Numerical secondary-outcome results are not reported in the registry record. The record lists 11 outcome measures and 0 analyses. The sponsor is Ferring Pharmaceuticals. No further design rationale, sample-size justification, or detailed analysis plan is 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: Safety Analysis Set

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 Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over For the overall 52-week Treatment Period.

The primary endpoint is the number of patients with adverse events (AEs) and serious adverse events (SAEs), measured in patients in the Safety Analysis Set over the overall 52-week treatment period. The registry describes recording all AEs from informed consent until the last visit, with information collected at each visit and each event entered in a patient-level AE log.

This is a count endpoint: it describes how many patients experienced an event in the specified categories. Counts can give a direct account of the observed burden of events in a study group. Reporting both AEs and SAEs separates the overall adverse-event category from events classified as serious in the record. The posted endpoint information does not define the criteria used to classify seriousness, so those criteria are not reported in the registry record.

A count does not convey every feature relevant to interpreting safety. It does not, on its own, describe the timing, duration, severity, recurrence, or treatment relationship of each event, nor does it indicate whether one patient had multiple events. The posted result gives patient counts, not a full event-level summary. As this is a single-group, open-label extension, the endpoint can describe what was recorded among participants in that group. It cannot, on its own, estimate a comparative difference against an untreated or alternative-treatment group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary patient-level event measure summarized as counts. For each category, a patient is counted as having experienced an event or not having experienced one during the specified period. The posted results give the number of patients with events and the number at risk. The registry record does not provide an inferential estimate, such as a confidence interval, for these counts.

What does a patient count capture?

A patient count answers how many individuals in the analyzed group were recorded as having at least one event in a category. It is not the same as counting every event episode. If one patient had multiple events, a patient-level count would still represent that individual as a patient with an event in that category. The record does not provide event-level totals or explain whether categories overlap, so those details are not reported in the registry record.

Counts are often useful for a descriptive safety summary because they retain a direct connection to the number of affected participants. Their interpretation depends on the denominator and the time period. Here, the reported denominator is 409 patients at risk for each category, and the period is the overall 52-week treatment period. Total enrollment is 411, while the primary outcome population is the Safety Analysis Set. The registry record does not explain participant flow between enrollment and this denominator or state how incomplete follow-up was handled.

Why does the study design matter?

In a randomized controlled trial, a comparison between groups can support an estimate of how outcomes differ between assigned interventions, subject to the design and analysis assumptions. This trial is recorded as single group, with allocation NA and no masking. There is no like-for-like concurrent control group in the posted results. The event counts therefore describe the group observed in the extension rather than a comparative treatment contrast. Differences from an external population or from a participant’s earlier experience are not reported and should not be inferred.

Open-label means the study was not masked, according to the registry’s design details. General statistical consideration: when study treatment is known, awareness can influence reporting, questioning, or assessment of subjective events. This is a general consideration, not evidence that ascertainment was biased in this trial. The registry describes investigator recording at each visit and use of an AE log but does not report blinded adjudication or other procedures that would quantify or address this possibility.

What does uncertainty mean for these results?

A confidence interval is a range of values generated by a statistical method to express uncertainty around an estimate. It helps readers distinguish a point estimate from the range of values compatible with the data under the method’s assumptions. No confidence intervals are reported for the posted safety counts. No p-values or comparative estimates are reported either. Therefore, the record does not support statements about statistical significance or the precision of a treatment difference.

General statistical consideration: a descriptive count is affected by the number of people observed and by how long they are followed. Exposure time can vary if participants have different follow-up, but participant-level time at risk is not reported. The stated outcome period is the overall 52-week treatment period; the registry record does not give individual treatment durations or person-time summaries. This makes it important not to interpret the counts as event rates per unit of exposure.

What can event categories tell readers?

The outcome distinguishes patients with AEs and SAEs, and the registry lists selected serious-event terms with percentages. A category label and its patient count do not explain event severity beyond the serious classification, whether an event was judged related to treatment, whether it resolved, or whether it led to treatment discontinuation. Those details are not reported in the registry record. The six listed terms are not a substitute for a complete event-level account.

General statistical consideration: analyses of safety data can use different units, including patients, event episodes, or exposure-adjusted rates. Each answers a different question. Patient counts describe the number of individuals affected, whereas event totals can reflect repeated events in one individual. Exposure-adjusted rates account for time under observation. The posted primary outcome is a patient count, and no event total or exposure-adjusted rate is reported.

How should planning calculations be understood?

Sample-size calculations can illustrate how many participants might be required to detect a specified effect under stated assumptions. They are planning exercises, not observed trial results or evidence that a study had a particular probability of detecting an effect. The registry record does not report a sample-size justification for this extension trial. Any planning illustration based on the observed outcome is separate from the trial’s own design rationale and cannot turn this single-group safety summary into a controlled comparison.

The record lists 11 outcome measures and 0 analyses. No detailed statistical analysis plan, model, adjustment strategy, or interim-analysis plan is reported in the registry record. Without those details, readers cannot assess whether particular choices were prespecified or how multiple outcomes and missing data were handled. The appropriate statistical reading is therefore descriptive: use the stated population, outcome definition, denominator, and observation period, and avoid extending the counts beyond those terms.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary safety outcome and secondary outcomes covering laxative use, global assessments, quality of life, and health status. It records 0 analyses. Numerical results for the secondary outcomes and a detailed analysis plan are not reported in the registry record. The record also does not state whether any multiplicity adjustment was planned or applied.

Multiplicity arises when several outcomes or analyses are considered: the more questions examined, the greater the chance that at least one result may appear notable by chance if each is interpreted independently. This is a general statistical issue, not a claim about the analyses conducted in this trial. Without a reported testing strategy, readers cannot determine how the listed outcomes were prioritized or how any inferential results would have been interpreted together. No inferential tests are included in the posted results.

Missing-data handling is also not reported in the registry record. The primary outcome population is named as the Safety Analysis Set, and the reported denominator is 409, compared with total enrollment of 411. The reason for this difference, participant-level follow-up, and any rules for including or excluding patients from the safety set are not stated. The record does not report whether participants with incomplete follow-up were counted, censored, or otherwise handled for the primary outcome.

These omissions limit evaluation of how representative the analyzed group is of all enrolled participants and whether the analysis choices could affect the reported counts. No assumptions about missingness or imputation can be made from the available record. The counts should therefore be interpreted in the named Safety Analysis Set, with the uncertainty about participant flow and missing-data procedures kept explicit.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (0.5%), anaemia (0.2%), constipation (0.2%), non-cardiac chest pain (0.2%), breast abscess (0.2%).

The registry reports 14 patients with serious adverse events among 409 at risk and 77 patients with other adverse events among 409 at risk in the EBX 10 group. Both counts refer to the overall 52-week treatment period. They are counts of patients, not counts of all event episodes, and the posted results do not say whether a patient could appear in both categories.

The record lists Appendicitis at 0.5%, and Anaemia, Constipation, Non-cardiac chest pain, Breast abscess, and Urinary tract infection at 0.2% each, among the serious-event terms. These entries do not provide a complete event narrative, nor do they establish a relationship between an event and study treatment. The registry record does not report the criteria for classifying an event as serious, event timing, duration, outcome, or treatment attribution.

Deaths are not reported in the registry record. The results also do not include a concurrent control group, confidence intervals, or event rates adjusted for time at risk. The safety figures should thus be read as descriptive counts in the analyzed group, rather than estimates of comparative risk or evidence about what would have occurred under another treatment.

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

The results document that investigators recorded serious and other adverse events among patients in the EBX 10 group over the overall 52-week treatment period. Specifically, the posted counts are 14 patients with serious adverse events and 77 patients with other adverse events, each among 409 at risk. The registry also names six serious-event terms with percentages. This is useful descriptive information about events observed and recorded in this extension trial.

The results do not establish that elobixibat caused any particular event. The record does not report treatment attribution for the events, and the single-group design has no concurrent comparator against which to estimate a difference. Nor do these counts establish that an event was prevented or increased relative to another treatment. They describe only the analyzed group and stated follow-up period.

The counts also do not fully characterize the safety experience. They are patient counts rather than event totals, and the record does not give event duration, severity beyond the SAE category, outcomes, recurrence, individual exposure time, or the number of deaths. The reason total enrollment of 411 differs from the 409 patients at risk is not reported. Confidence intervals and other measures of statistical uncertainty are not reported for the primary outcome.

The trial title refers to 5 mg and 10 mg daily, but the listed intervention and arm describe 10 mg; details for a 5 mg group are not reported in the registry record. Numerical results for the named secondary outcomes are also not reported. Consequently, the record does not support conclusions about comparative effects, changes in constipation symptoms, quality of life, or health status. Its contribution is a descriptive account of the safety counts that were posted, with substantial limits on causal and comparative interpretation.

13. Why This Trial Matters Statistically

Extension trials can add information about events observed during a stated treatment period in a study population. In this record, the primary outcome is explicitly a safety count over the overall 52-week treatment period, and investigators recorded events from informed consent through the last visit. This makes the endpoint and observation window central to interpretation: the figures describe patients recorded with events during that period, rather than treatment effects against a control.

The trial is also a useful example of why design labels and denominators matter. It is open-label and single group, with allocation marked NA. These features constrain the kinds of statistical claims the posted results can support. The counts are meaningful as descriptive observations, but they cannot by themselves establish a comparative difference. Recognizing that boundary prevents a patient count from being mistaken for a causal estimate.

The record also illustrates the importance of aligning the trial population with the analyzed population. Enrollment is 411, while the safety results use 409 patients at risk. The registry names the Safety Analysis Set but does not explain the difference in denominators. That missing explanation matters for judging completeness and understanding precisely which participants contribute to the outcome.

Finally, the listing of secondary measures alongside 0 analyses emphasizes that outcome names do not substitute for numerical results or analysis methods. Without reported secondary estimates, uncertainty measures, multiplicity procedures, and missing-data rules, readers cannot evaluate those outcomes statistically. The trial’s statistical value is therefore best framed narrowly: it records safety counts in a defined single-group extension setting and shows why design, outcome scale, analysis population, and reporting completeness must be considered together.

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.

Several limitations specific to this trial affect interpretation of its posted results. It is a single-group, open-label extension with allocation recorded as NA and no concurrent control. This prevents a like-for-like comparison and limits causal interpretation of the observed adverse-event counts. The registry record does not describe blinded event assessment or an independent adjudication process.

The endpoint is a patient count over the overall 52-week treatment period. The record does not provide total event episodes, event timing, duration, treatment relationship, outcomes, or individual exposure time. It also does not report a number of deaths. The criteria used to classify serious events are not reported in the registry record.

Total enrollment is 411, while the safety results identify 409 patients at risk. The registry names the Safety Analysis Set but does not explain the difference or provide participant flow and follow-up completeness. Missing-data handling and rules for inclusion in the safety population are not reported.

The official title refers to 5 mg and 10 mg daily, but the listed intervention and arm are for elobixibat 10 mg. Details of a 5 mg arm are not reported in the registry record. The record lists 11 outcome measures and 0 analyses, while numerical secondary-outcome results, confidence intervals, hypothesis tests, and a detailed statistical analysis plan are not reported. Sample-size justification and interim-analysis procedures are also not reported in the registry record. These gaps limit assessment of precision, planned analyses, and the scope of conclusions that can be drawn.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Tolerability Extension Trial for Patients With Chronic Idiopathic Constipation — NCT01895543.
• Registry record last updated 2016-05-09; status last verified 2016-04.
• Results first posted 2016-05-09.
• 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

NCT01895543 is a completed Phase 3, multicenter, open-label, single-group extension trial in chronic idiopathic constipation. Total enrollment is 411. The recorded start was 2013-09 and primary completion was 2015-05. The official title refers to elobixibat 5 mg and 10 mg daily, while the listed arm and intervention identify elobixibat 10 mg.

The primary outcome is the number of patients with AEs and SAEs over the overall 52-week treatment period, in the Safety Analysis Set. The EBX 10 group reports 14 patients with serious adverse events and 77 with other adverse events, each among 409 at risk. The record lists 11 outcome measures and 0 analyses. Numerical results for secondary outcomes and further details on the analysis plan, missing data, and participant flow are not reported in the registry record. With no concurrent comparator, the posted safety counts are descriptive rather than comparative.