Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety "Roll-over" Study (Rollover): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety "Roll-over" Study (Rollover) (NCT04483479), a na phase 2 study. The primary outcome is Number of Participants With Treatment Related Adverse Events.

2. Clinical Question

3. Trial Design

This was a Phase 2, multicenter, non-randomized, open-label, single-group follow-on study of orally administered ENT-01. Its stated purpose was to evaluate safety and efficacy for constipation and neurologic symptoms in people with Parkinson disease and constipation over a 14-week period. The brief summary describes it as a safety follow-on to a multicenter, double-blind, randomized study, with participants from that study offered entry into the unblinded follow-on.

The brief summary anticipated approximately 50 participants. The registry lists enrollment of 27. These are different descriptions of planned and recorded enrollment; the registry does not explain the difference. The study is listed as terminated. The reason for termination and any consequences for the planned conduct are not reported in the registry record.

ENT-01 was administered daily in escalating doses followed by a fixed dose for 12 weeks, according to the brief summary. The active-treatment description specifies an oral 25mg tablet once daily, with dose dependent on ENT-01-030 dose-level stratification. The brief summary gives approximately 20 weeks for each participant’s study participation and approximately 14 weeks for dosing. The primary endpoint timeframe is through study treatment and completion up to 14 weeks.

Because there was no randomized allocation or concurrent control group, the study describes participants’ experience during the follow-on rather than estimating a controlled treatment contrast. The registry does not report the reasons for termination, details of dose-level groups, or a statistical analysis plan.

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

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 Participants With Treatment Related Adverse Events, measured over Through study treatment and completion up to 14 weeks.

The primary endpoint is the number of participants with treatment-related adverse events. It is a count of participants, rather than a count of every event: a participant with multiple events could still contribute as a participant with an event. The endpoint’s stated observation window is through study treatment and completion up to 14 weeks.

Counting participants with treatment-related events is a way to describe how many people experienced events judged related to treatment during the defined follow-up. Such a measure can be useful in a safety-focused study because it summarizes the reach of reported events across participants. It does not, by itself, describe the number, severity, duration, or clinical importance of events, nor does it establish that treatment caused an event.

The registry record does not report a numerical result for this designated endpoint, nor does it provide its operational definition or explain how treatment relationship was determined. The adverse-event summary reports separate serious and other adverse-event counts. Those figures provide safety information, but do not supply the missing primary-endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count measure?

A participant count records whether people met an event definition during a specified observation period. It differs from an event count: a person can experience multiple events but may be counted once in a participant-level summary. The primary endpoint is explicitly a count of participants with treatment-related adverse events, whereas the adverse-event summary separates serious and other events. The registry record does not report enough detail to reconcile those summaries or identify the participant-level primary result.

Why is the study design important?

In a randomized comparison, treatment groups are formed by random allocation, which can support an estimate of the difference between groups under the study design. This study is described as non-randomized and single-group, with allocation listed as not applicable. There is no concurrent control group against which to estimate a treatment contrast. Therefore, the safety counts describe the active-treatment group, rather than an effect attributable to ENT-01 relative to another condition.

The study is also open-label. In general, knowledge of treatment assignment can influence reporting, assessment, or decisions about whether an event is considered related to treatment. This does not show that such influence occurred in this study; it is a design consideration when interpreting unblinded safety data. The registry does not report procedures for event assessment or attribution.

What do the at-risk figures mean?

The safety summary lists 27 participants at risk for serious adverse events and 27 at risk for other adverse events. An at-risk denominator identifies the group against which the corresponding affected-participant count is presented. It should not automatically be interpreted as proof that every participant completed the full follow-up period. The registry does not report individual follow-up duration, censoring, or the handling of participants with incomplete observation.

How should uncertainty be understood?

A confidence interval, in general, expresses the statistical uncertainty around an estimate under specified assumptions. The registry record does not report a confidence interval for the serious-event or other-event count, or for the primary endpoint. With no reported inferential analysis, the counts alone do not quantify the precision of an underlying event rate. A zero observed count also does not establish that the event could never occur; it records no affected participants in the listed group during the reported observation context.

What is the role of sample-size planning?

Any sample-size illustration is a planning calculation, not a result observed in participants and not a measure of achieved power. The registry’s stated illustration assumptions refer to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detecting a stated fraction of an observed effect. Those assumptions do not describe the actual single-group, non-randomized design. No planning output is included in the registry entries, and the observed effect needed for such an illustration is not reported as a numerical result.

In general, over-dispersion means that variation in count data exceeds what a simple model assumes; accounting for it can affect standard errors and uncertainty estimates. The registry does not report a count model or dispersion estimate. The primary endpoint is a participant count, and no statistical model is reported, so no model-based interpretation should be inferred.

Are adjusted analyses available?

The registry lists no analyses. It therefore does not report adjusted estimates, unadjusted hypothesis tests, confidence intervals, or a model for the primary endpoint. Nor does it state whether planned analyses were performed outside the registry. Without those details, interpretation should remain at the level of the posted descriptive safety counts and study 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("Active Treatment")
n      <- c(27)
events <- c(23)
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  Active Treatment  27  23  85.2  66.3  95.8  67.5  94.1  67.3  93.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy. It lists four outcome measures but no analyses, and does not state whether outcomes were tested in a hierarchy, whether any adjustment for multiple testing was planned, or whether results were intended to be exploratory. General statistical practice recognizes that testing multiple outcomes can increase the chance of at least one apparently notable result, but no such testing results are reported for this study.

Missing-data procedures are not reported in the registry record. The record does not describe how incomplete follow-up, missed assessments, or withdrawal would be handled, and it does not give participant-level follow-up information. The at-risk figures do not establish that every participant was observed for the full endpoint timeframe.

The analysis population is also not reported in the registry record. Although enrollment is listed as 27 and the safety summary gives at-risk figures of 27, the record does not explain the analysis-set definition or how participants entered the safety summaries. It does not state whether all enrolled participants were included in each outcome analysis.

These omissions limit assessment of how outcomes were selected, how incomplete records affected the results, and whether analyses matched any prespecified plan. The registry lists no analyses, so it is not possible to evaluate analytic choices or reconstruct a primary-endpoint estimate from the record.

12. 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 non-serious adverse event terms

The safety summary lists 0 participants with serious adverse events among 27 at risk and 24 participants with other adverse events among 27 at risk. The summary also lists 0 deaths. These are counts for the active-treatment group, not a comparison between treatment groups. The registry does not list serious adverse-event terms.

Seriousness and treatment relationship are different classifications. The primary endpoint concerns treatment-related adverse events, but the safety summary’s serious-versus-other categories do not establish whether events were judged related to ENT-01. The registry record does not report the numerical primary-endpoint result or the relationship classification for each event category.

Participant counts are also not the same as counts of individual events. The count of participants with other adverse events does not reveal how many events occurred, how severe they were, when they occurred, or whether some participants experienced more than one event. The registry record does not provide those details in this safety summary.

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

The posted results establish that the registry lists 27 participants at risk in the active-treatment group, with 0 participants reported with serious adverse events, 24 with other adverse events, and 0 deaths. These are descriptive safety figures for the follow-on study. The study’s open-label, single-group design gives no concurrent control for interpreting those counts as a treatment effect.

The record does not establish that ENT-01 caused the reported events, nor does it establish that the absence of reported serious adverse events means such events are impossible. The counts are tied to the study’s reporting and observation context, and the registry does not report detailed event terms, individual follow-up, or the process used to assess relatedness.

The designated primary endpoint is treatment-related adverse events, but its numerical result is not reported in the registry record. Consequently, the safety summaries cannot be used as a substitute for that result. The record also does not provide an inferential analysis or confidence interval for these counts, so their precision cannot be assessed from the posted information.

The study’s stated aim included constipation and neurologic symptoms, but no efficacy result is included in the registry entries. The available information therefore does not support a conclusion about change in those symptoms. More generally, a single-group follow-on study can describe outcomes among participants who entered it, but without a concurrent comparator it cannot distinguish treatment-associated changes from other influences.

The record lists the study as terminated, without reporting a reason. That status is relevant context, but the record does not explain whether termination changed follow-up, outcome availability, or the analysis. Interpretation should remain limited to the reported design and descriptive counts.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a safety count and a treatment-effect estimate. Reporting how many participants experienced an event can describe the observed safety experience, but a single-group study does not provide the concurrent comparison needed to estimate how that experience differs under another treatment or no study treatment.

It also highlights why endpoint definitions matter. The primary outcome is the number of participants with treatment-related adverse events, while the posted safety summary separates serious events from other adverse events. Those classifications answer different questions. Without the primary-endpoint result or further detail on event relatedness, the safety counts cannot be treated as a direct estimate of the designated endpoint.

The rollover context is statistically important as well. Participants were drawn from a preceding randomized study, but this follow-on study itself is described as non-randomized and open-label. The prior study’s design does not make the rollover study a randomized comparison. Its participants’ selection into follow-on participation and the absence of a control arm limit what can be inferred from the follow-on counts.

Finally, the registry lists no analyses, and does not report missing-data procedures, analysis populations, or a multiplicity strategy. These details affect how estimates and uncertainty should be interpreted. The record’s limited descriptive reporting makes careful separation of observed counts, the unreported primary endpoint, and broader claims especially important.

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.

Specific limitations arise from the registry record’s limited outcome detail. The primary endpoint is defined as the number of participants with treatment-related adverse events, but its numerical result is not reported. The serious and other adverse-event counts do not provide a replacement because the record does not connect those categories to treatment relatedness.

The study has no concurrent comparator and is open-label. Its counts therefore cannot support a controlled estimate of the effect of ENT-01, and reporting or assessment may be influenced by the unblinded design. The registry does not describe event adjudication, the operational definition of treatment-relatedness, or individual event details.

The listed enrollment is 27, while the brief summary anticipated approximately 50 participants. The registry does not explain this difference. The status is terminated, but the reason and its implications for follow-up or data availability are not reported. It is therefore not possible to determine from the record whether the planned observation was completed as intended.

The record does not report the analysis population, missing-data handling, participant-level follow-up, confidence intervals, hypothesis tests, or statistical models. It also does not report the numerical efficacy results mentioned in the study’s stated aims. These gaps limit assessment of precision, completeness, and the relationship between the planned outcomes and the posted safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Orally Administered ENT-01 for Parkinson's Disease-Related Constipation Follow-on Safety "Roll-over" Study (Rollover) — NCT04483479.
• Registry record last updated 2024-03-19; status last verified 2024-02.
• Results first posted 2024-03-19.
• 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 this Phase 2 study as a multicenter, non-randomized, open-label, single-group follow-on study of orally administered ENT-01 in people with Parkinson disease and constipation. It is listed as terminated, with enrollment of 27. The brief summary describes daily escalating doses followed by a fixed dose for 12 weeks and approximately 14 weeks of dosing.

The primary endpoint was the number of participants with treatment-related adverse events through treatment and completion up to 14 weeks. Its numerical result is not reported in the registry record. The safety summary lists 0 participants with serious adverse events, 24 with other adverse events, and 0 deaths among 27 at risk. No analyses are listed. The record does not report a reason for termination, an analysis population, or missing-data procedures.