Long-Term Safety and Tolerability of Mesalamine Pellets in Participants With Ulcerative Colitis in Remission: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-Term Safety and Tolerability of Mesalamine Pellets in Participants With Ulcerative Colitis in Remission (NCT00326209), a na phase 3 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

This is a safety and tolerability question, not a randomized comparison of treatment with a control. The registry describes an open-label treatment extension and identifies the study as Phase 3. Its brief summary states that participants had ulcerative colitis in remission when the study aimed to evaluate long-term safety and tolerability of eMG, formerly referred to as Mesalamine Pellets.

The central interpretive issue is therefore descriptive: what adverse events were recorded among the participants represented in the safety summaries? Because no comparator group is recorded, the data cannot directly estimate how event frequency would differ under another treatment or under no study treatment. The registry record also does not report a causal assessment for each event in the primary endpoint definition; an adverse event was counted without regard to whether it was considered related to study drug.

3. Trial Design

The registry describes a multicenter, open-label treatment extension trial of eMG in participants with ulcerative colitis in remission. It lists the study as Phase 3, completed, and single-group. Enrollment is recorded as 393. The trial began on 2005-12-22, and primary completion is recorded as 2008-05-05. The registry does not list a randomized allocation or masking; allocation is recorded as not applicable and masking as none.

The intervention description specifies oral eMG 1.5 grams, taken once daily in the morning as 4 capsules of 0.375 grams each, for up to 24 months. The primary endpoint timeframe is Baseline (Day 1) up to follow-up (24.5 months). That endpoint timeframe and the intervention duration are related but not identical descriptions; the registry gives both and does not explain the distinction further.

The primary endpoint is the number of participants with treatment-emergent adverse events. The registry defines an adverse event as an untoward medical occurrence in a participant who received study drug, regardless of the possibility of a causal relationship. An event qualifies as treatment-emergent if it starts on or after treatment Day 1, or if it was pre-existing and worsens after Day 1.

The safety population is defined as participants who received at least 1 dose and had at least 1 post-baseline safety assessment. The adverse-event summary lists 388 participants at risk. The registry enrollment figure and the safety-summary population describe different record elements; the registry does not provide a participant-flow explanation for the difference.

Because this is a single-group, open-label study, its safety summaries describe events observed during the study rather than a treatment contrast. The registry record does not report the study protocol, a sample-size justification, or details of how participants entered the extension.

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: A total of 393 participants were enrolled into the study. Of the participants included in the study, 280 participants were rolled over from a lead-in study (MPUC3003 or MPUC3004) and 113 were new participants.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.

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 population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs), measured over Baseline (Day 1) up to follow-up (24.5 months).

The primary endpoint counts participants with treatment-emergent adverse events over the stated timeframe, from Baseline (Day 1) up to follow-up (24.5 months). It uses a participant count rather than a measure of symptom intensity or a rate per unit of follow-up. An event is considered treatment-emergent based on when it begins, or whether a pre-existing event worsens after treatment Day 1. The definition does not require the event to be judged caused by study drug.

Counting participants with an event is useful for describing how widely events were observed in the safety population. It distinguishes the number of people affected from the total number of event episodes, which the endpoint title does not measure. A participant may experience more than one event, but the participant-count endpoint does not provide an event total or show how events were distributed within each participant.

The registry also distinguishes serious adverse events from other non-serious adverse events. Serious events are defined by outcomes or clinical importance, including death, a life-threatening event, hospitalization or prolonged hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or another important medical event requiring intervention to prevent a listed outcome.

The registry record names the primary endpoint but does not give a separate overall primary-endpoint count in the outcome information available for this analysis. The adverse-event summaries do give counts for participants with serious and other non-serious events. Those categories should not be treated as a complete substitute for a separately reported total for all treatment-emergent adverse events.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: a single-group safety study describes what happened among participants receiving the study intervention. Its basic summaries can include the number of participants with an event and the number represented in the safety population. Such summaries answer a descriptive question. They do not, by themselves, estimate a treatment effect relative to a comparator.

What does the participant count represent?

The primary endpoint is framed as a count of participants with treatment-emergent adverse events. This is a participant-level measure: a person with several qualifying events remains a participant with an event for this endpoint. The count therefore differs from an event total, which would count each episode, and from an event rate, which would account for time at risk. The registry names a participant-count endpoint but does not report a separate overall count for it in the outcome information.

The adverse-event summary separately lists participants at risk and participants affected for serious and other non-serious events. A denominator gives context for an observed count, but the registry record does not provide confidence intervals for these summaries. Nor does it report a model-based estimate that adjusts for follow-up time or participant characteristics. The reported figures should therefore be read as descriptive results rather than as outputs of a comparative statistical model.

Why does the study design matter?

In a randomized comparative study, allocation can support a direct comparison between groups, subject to the trial's design and analysis assumptions. This record instead describes a single-group study, with allocation listed as not applicable and masking listed as none. There is no concurrent control arm in the registry record. Consequently, no between-group treatment contrast can be estimated from these summaries.

Open-label status means the study is not recorded as masked. General statistical explanation: awareness of treatment assignment can affect event recognition, reporting, clinical decisions, or follow-up. This possibility does not show that reporting was biased in this trial; it identifies a consideration when interpreting an unmasked safety record. The registry does not report procedures used to standardize adverse-event ascertainment.

What is a confidence interval?

General statistical explanation: a confidence interval expresses uncertainty around an estimate using a method with specified assumptions. It helps readers distinguish the observed estimate from the range of values compatible with the data under that method. A narrow interval generally indicates greater statistical precision than a wide interval, although precision is not the same as freedom from bias. The registry record does not report confidence intervals for the adverse-event counts or listed percentages.

A significance test would address a specified statistical hypothesis, usually in the context of a defined comparison. No comparative hypothesis test is reported in the registry record. The record lists no analysis entries. This absence does not establish what analyses may have been conducted outside the registry; it means those analyses are not reported in the registry record.

How should event categories be read?

The registry defines an adverse event broadly as an untoward medical occurrence after receipt of study drug, without requiring a causal connection. Treatment-emergent status depends on timing or worsening after treatment Day 1. Seriousness is classified using listed outcomes and criteria, including hospitalization, life-threatening events, and certain important medical events. Seriousness and relatedness are different concepts: an event can meet seriousness criteria without the registry establishing that the study drug caused it.

General statistical explanation: a summary of participants with an event does not convey how long each participant was observed, when the event occurred, whether it recurred, or whether treatment was stopped. Time-to-event methods can incorporate the timing of events and censoring, while a simple participant count does not. The registry does not report such an analysis for these safety summaries. The stated follow-up timeframe is Baseline (Day 1) up to follow-up (24.5 months), and the intervention was planned for up to 24 months.

What do planning illustrations mean?

General statistical explanation: sample-size calculations estimate how many participants a future study might need under specified assumptions about an effect, allocation, significance level, and statistical method. They are planning illustrations, not observed power and not evidence that the current study had a particular probability of detecting an effect. The registry record does not report the trial's own sample-size justification. Any planning illustrations based on an observed effect should be understood as separate from the trial's design and should not be mistaken for results from a randomized comparison in this single-group study.

The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. Those assumptions do not turn the single-group record into a two-arm comparison. The record does not report a trial analysis plan or give a basis for assessing whether those planning assumptions reflect the study's original design.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Encapsulated Mesalamine Granules (eMG)")
n      <- c(388)
events <- c(280)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Encapsulated Mesalamine Granules (eMG)  388  280  72.2  67.4  76.6  67.5  76.4  67.5  76.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures and no analysis records. It does not report how the outcomes were prioritized beyond identifying the primary endpoint, nor does it describe a procedure for controlling multiplicity across outcomes or analyses. Without a reported multiplicity strategy, the registry record does not establish how repeated statistical testing, if any, was handled. No set of reported hypothesis tests is available to evaluate.

Missing-data methods are not reported in the registry record. The record defines the safety population as participants who received at least 1 dose and had at least 1 post-baseline safety assessment, but does not describe how participants without later assessments were handled, how incomplete event information was treated, or whether follow-up differed across participants. These omissions matter because a participant-count summary depends on who was observed and on how events were captured.

The registry enrollment figure is 393, while the adverse-event summaries list 388 participants at risk. The record does not explain participant flow between those figures, and it does not report reasons for non-inclusion in the safety summaries. It would therefore be inappropriate to infer why the figures differ or to assume that missing safety information had no effect on the summaries.

The record does not report an intention-to-treat population or a separate efficacy population. The stated safety-population definition is the population description available for interpreting the safety results. The registry also does not report a statistical analysis plan, sensitivity analyses, imputation methods, or procedures for handling multiple events within a participant. These matters are not reported in the registry record.

12. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: colitis ulcerative (1.5%), cellulitis (0.8%), atrial fibrillation (0.5%), upper limb fracture (0.5%), abortion spontaneous (0.5%).

The adverse-event summary lists 388 participants at risk for serious events, with 28 listed as having serious adverse events. For other non-serious adverse events, it lists 388 at risk and 280 affected. These are participant counts in the registry summary. They are not counts of every event episode, and they do not compare eMG with a control treatment.

The serious-event terms listed include Colitis ulcerative (1.5%), Cellulitis (0.8%), Atrial fibrillation (0.5%), Upper limb fracture (0.5%), Abortion spontaneous (0.5%), and Ectopic pregnancy (0.5%). The registry provides these percentages but does not provide corresponding counts for each listed term in the record. The terms should not be interpreted as treatment-caused events: the registry's adverse-event definition does not require causal attribution.

Seriousness refers to the registry's criteria, including death, life-threatening events, hospitalization or its prolongation, significant disability or incapacity, congenital anomaly or birth defect, and other important medical events requiring intervention to prevent a listed outcome. The registry does not report a death count in this summary. That is different from establishing that no deaths occurred.

The record does not provide event-level timing, duration, recurrence, or participant-level detail in these summaries. Consequently, the counts and listed terms describe reported safety categories but do not fully characterize the clinical course of the events.

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

The results mean that the registry records serious and other non-serious adverse-event summaries among participants in the eMG safety population during the study's stated follow-up. The serious-event summary lists 28 affected participants among 388 at risk, and the other non-serious summary lists 280 affected among 388 at risk. The registry also lists selected serious-event terms with their percentages. These are observations from a single-group, open-label extension study.

They do not show how those figures compare with what would have happened under another treatment or without study treatment. The design has no comparator group, so a comparative treatment effect cannot be estimated from the registry summaries. The figures also do not establish causality. The registry's definition counts adverse events irrespective of the possibility that study drug caused them, and the record does not provide event-specific causal assessments in the information.

The primary endpoint is defined as the number of participants with treatment-emergent adverse events, but a separate overall result for that endpoint is not reported in the registry record. Serious and other non-serious event summaries are informative in their own right, but they should not be assumed to equal the overall primary endpoint. The record does not clarify whether all events in those summaries meet the primary endpoint's timing criteria.

General statistical explanation: a descriptive count can help characterize the experience observed in a study, but it is not a causal estimate. A causal interpretation requires a design and analysis that support comparison while addressing alternative explanations. Even a precise estimate of an event frequency would not by itself establish whether treatment caused the event or whether the frequency differs from that under another option.

The record therefore supports a bounded conclusion: adverse events were recorded and categorized during an open-label extension in participants with ulcerative colitis in remission. It does not establish comparative safety, a causal relationship between eMG and specific events, or the event experience of all participants who might receive the intervention in other settings. The registry does not report the missing-data methods, event-level details, or statistical uncertainty needed to extend interpretation beyond those descriptive summaries.

14. Why This Trial Matters Statistically

This trial is statistically important to read as a descriptive safety study rather than as a treatment comparison. Its single-group design sets the scope of inference: the registry can report what was observed in the enrolled study population, but it cannot supply a concurrent estimate of what would have occurred under a different treatment. Recognizing that distinction prevents event counts from being mistaken for evidence of a comparative effect.

The distinction between an endpoint definition and an endpoint result also matters. The registry specifies a primary outcome based on participants with treatment-emergent adverse events, including clear timing rules, but a separate overall count for that endpoint is not reported in the outcome information. The serious and other non-serious summaries add safety information without resolving that reporting gap.

The record also illustrates why population definitions and denominators need attention. Enrollment is recorded as 393, while the safety summaries list 388 participants at risk. The safety population has a specific definition based on exposure and a post-baseline assessment, but the registry does not explain participant flow between the enrollment and summary figures. Without that explanation, the figures should be reported as they appear rather than reconciled by assumption.

Finally, seriousness, treatment emergence, and causality are separate dimensions. A serious event meets criteria related to its consequences or medical importance. A treatment-emergent event meets the stated timing rule. Neither label by itself proves that study drug caused the event. Keeping these concepts distinct is essential when interpreting safety data from an open-label, non-comparative study.

15. 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 design is single-group and open-label, with no comparator recorded. As a result, the safety summaries cannot distinguish events associated with the study intervention from events arising from the underlying condition, other exposures, or other circumstances. The registry does not report an adjusted comparison or a causal analysis.

The primary endpoint is defined, but a separate overall count for participants with treatment-emergent adverse events is not reported in the registry record. The available summaries distinguish serious events from other non-serious events, and the record does not state whether those categories capture all events meeting the primary endpoint definition.

The registry enrollment figure is 393, whereas the safety summaries list 388 participants at risk. The record defines the safety population but does not explain participant flow or reasons for the difference. It does not report missing-data handling, participant-level follow-up, or whether all participants were observed for the same duration. These details limit interpretation of the event counts.

The record does not report confidence intervals, a statistical analysis plan, a sample-size justification, or details of adverse-event ascertainment beyond the event definitions. It also does not provide a death count in the safety summary. The absence of a reported death count should not be read as confirmation that no deaths occurred.

The listed serious-event terms and percentages do not provide the full event-level context, such as timing, duration, recurrence, or individual attribution. The registry describes the study as a treatment extension but does not report details of the participants' route into the extension or prior treatment history. These limitations restrict conclusions to the descriptive safety information recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long-Term Safety and Tolerability of Mesalamine Pellets in Participants With Ulcerative Colitis in Remission — NCT00326209.
• Registry record last updated 2019-11-01; status last verified 2019-10.
• Results first posted 2019-11-01.
• 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.

19. Record Summary

The registry identifies NCT00326209 as a completed Phase 3, multicenter, open-label, single-group treatment extension trial of encapsulated mesalamine granules in participants with ulcerative colitis in remission. Enrollment is listed as 393. The intervention is described as eMG 1.5 grams orally once daily for up to 24 months. The primary endpoint is the number of participants with treatment-emergent adverse events from Baseline (Day 1) up to follow-up (24.5 months).

The adverse-event summaries list 388 participants at risk for serious events, with 28 affected, and 388 at risk for other non-serious events, with 280 affected. The registry also lists selected serious-event terms and percentages. It does not report a separate overall result for the primary endpoint, a comparator group, statistical analysis details, missing-data methods, or a sample-size justification. The results are therefore descriptive safety observations, not a comparative estimate or evidence of causality.