Evaluation of the Safety of Lubiprostone in Pediatric Participants Aged ≥ 6 Years to < 18 Years With Functional Constipation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Safety of Lubiprostone in Pediatric Participants Aged ≥ 6 Years to < 18 Years With Functional Constipation (NCT02766777), a na phase 3 study. The primary outcome is Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE).

2. Clinical Question

3. Trial Design

This phase 3 study evaluated lubiprostone in pediatric participants with functional constipation. Its official title describes it as a multicenter, 6-month, open-label safety study. The registry classifies the design as single-group, with no masking and allocation marked NA. It lists 87 participants as enrolled.

Participants received lubiprostone twice daily, at 12 mcg or 24 mcg according to participant weight, for up to 24 weeks. The listed primary outcome uses a timeframe of within 25 weeks. These are distinct descriptions: the title calls the study 6-month, the treatment description specifies up to 24 weeks, and the outcome timeframe is within 25 weeks.

The study began on 2016-04-12, had a primary completion date of 2016-11-04, and is recorded as completed. Sucampo Pharma Americas, LLC is listed as the sponsor. The record identifies no randomized allocation and no comparison arm. Consequently, the design can describe adverse events recorded among participants who received lubiprostone, but it cannot establish how those outcomes compare with a concurrent control group. Further details about recruitment, follow-up procedures, or the rationale for the sample size are not 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 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: Safety (SAF) population, defined as all enrolled participants who took at least one dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE), measured over within 25 weeks.

The primary outcome is the number of participants with at least one treatment-emergent adverse event, measured within 25 weeks. It is a participant count: each person is counted according to whether at least one qualifying event occurred, rather than by the total number of events experienced. The registry defines treatment-emergent events by timing: onset must be after the first dose of study medication or before the last day of treatment plus 7 days.

Safety outcomes of this kind are used to describe events observed during and shortly after treatment exposure. Counting participants with an event gives a direct description of how many people experienced one or more qualifying events, but it does not convey how many separate events occurred or their duration or severity. Those details require separate results.

The registry record names the endpoint and its timeframe but does not report its numerical result. It therefore does not establish how many participants met the primary outcome definition. The safety population is identified, but additional details about how that population was defined are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is listed?

As a general statistical point, a binary outcome records whether a defined condition occurred for each participant. For this study, the condition is having at least one treatment-emergent adverse event during the stated timeframe. The primary outcome is expressed as a count of participants, not a continuous measurement such as a laboratory value. A participant with multiple qualifying events would still meet the “at least one” definition, although the registry record does not report event totals or participant-level detail.

For a binary outcome, researchers commonly describe both the number of participants meeting the definition and the number assessed. Those quantities allow readers to understand the observed proportion. The registry record identifies a safety population and reports 87 participants at risk in the adverse-event groupings, but it does not report the numerical primary outcome result. No primary-outcome proportion can therefore be quoted from this record.

What does treatment-emergent mean?

The event definition depends on timing relative to study medication. Events with onset after the first dose or before the last day of treatment plus 7 days are considered treatment-emergent. This definition specifies which events count for the outcome; it does not by itself establish that the medication caused an event. The timeframe for the primary outcome is within 25 weeks. The registry does not provide further information about event adjudication or the methods used to determine whether an event met the definition.

What can a single-group study estimate?

As a general statistical point, a single-group study can describe outcomes among participants receiving the study intervention. A concurrent comparator is needed to estimate a between-group contrast and to help distinguish treatment-associated outcomes from the background rate of similar events. This study is recorded as single-group, with allocation NA and no masking. Its adverse-event counts are therefore descriptive; they do not estimate a randomized treatment effect.

In general, random allocation can help balance measured and unmeasured characteristics between groups, while masking can reduce some influences on reporting and assessment. Neither feature is present in the design recorded for this study. That does not invalidate the descriptive safety observations, but it narrows the conclusions that can be drawn from them. Details of any alternative methods to address confounding or reporting differences are not reported in the registry record.

What do the planning calculations represent?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are calculated from an observed effect, with the target effect set as a stated fraction of that effect. These assumptions describe a hypothetical planning exercise, not the design recorded for this single-group study. The registry record does not report that this study used those assumptions to choose its enrollment target or that it had a two-arm comparison.

Such calculations are planning illustrations, not observed power. They do not show the probability that this completed study detected an effect, and they cannot create a valid control comparison where the study did not include one. The numerical planning values are not repeated in this explanation. The study’s sample-size justification is not reported in the registry record.

What uncertainty information is available?

As a general statistical point, a confidence interval describes the precision of an estimate under a statistical model. A narrow interval indicates greater precision than a wide interval, while an interval that spans many plausible values signals greater uncertainty. The registry record does not report a confidence interval or a statistical analysis for the primary outcome. It lists no analysis entries. Consequently, readers cannot use this record to assess the statistical precision of the primary result or to evaluate a formal hypothesis test for that outcome.

For adverse-event counts, precision also depends on how many participants were observed and on the event frequency. General statistical methods can quantify that uncertainty, but no such interval is reported for the figures in this record. The reported counts should be read as observed counts, not as precise estimates of event frequency in a broader population.

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("Lubiprostone")
n      <- c(87)
events <- c(47)
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  Lubiprostone  87  47  54.0  43.0  64.8  43.6  64.1  43.6  64.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure: the number of participants with at least one treatment-emergent adverse event. It lists no analysis entries. A single listed outcome does not establish that no other outcomes were collected or examined, and the registry record does not report a multiplicity plan. Multiplicity refers, in general, to the challenge of interpreting results when several outcomes or statistical tests are considered. Without the analysis plan, it is not possible to determine whether any adjustment for multiple testing was intended or used.

The numerical result for the listed primary outcome is not reported in the registry record. The record also does not report how missing outcome information was handled, whether any data were imputed, or how participants with incomplete follow-up were treated in the analysis. These omissions matter because the observed count may depend on which participants had outcome information available and how the analysis population was defined.

The primary outcome identifies the safety population, while the adverse-event results list 87 participants at risk. The record does not provide further details about the safety-population definition, participant-level follow-up, or completeness of event reporting. It does not report an intention-to-treat analysis population or describe whether other analysis populations were used. The enrollment figure alone does not establish that every participant contributed complete outcome data.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: colitis ulcerative (1.1%), constipation (1.1%).

The registry reports 2 participants affected by serious adverse events among 87 at risk. For other adverse events, it reports 24 participants affected among 87 at risk. It reports 0 deaths. These are participant counts, not totals of all event occurrences. A person could experience more than one event, and the registry record does not state whether the serious and other categories include any of the same participants.

The listed top serious adverse event terms are “Colitis ulcerative” and “Constipation,” each reported as 1.1%. These percentages are presented as registry results and should not be treated as proof of a causal relationship to lubiprostone. The study had no control group, so the figures cannot be compared with a concurrent untreated or differently treated group.

The primary endpoint is broader than the serious-event count: it concerns participants with at least one treatment-emergent adverse event. Its numerical result is not reported in the registry record. The serious-event figures do not fill that gap, because they are a separate safety summary and do not indicate how many participants experienced any treatment-emergent event.

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

The record establishes that a phase 3, open-label, single-group study enrolled 87 pediatric participants with functional constipation and administered lubiprostone twice daily at a weight-based dose of 12 mcg or 24 mcg. It reports serious and other adverse-event participant counts, lists two serious-event terms with percentages, and records 0 deaths. These results are observations from the participants in this study.

The record does not report the numerical result for the primary outcome, which asks how many participants had at least one treatment-emergent adverse event within 25 weeks. It also provides no concurrent control group. Therefore, the available figures cannot establish how the frequency of adverse events compares with another treatment or with no study treatment. Nor do they establish that a particular event was caused by lubiprostone.

The design and reported outcomes concern safety. They do not provide a basis for conclusions about whether lubiprostone improves constipation or how it compares with other options. No advice about an individual’s care follows from these registry results. The interpretation is bounded by the record’s reported counts and by the absence of a primary-endpoint result, comparator, and details about missing data or statistical analysis.

In general, registry results are most informative when the outcome definition, analysis population, missing-data approach, and uncertainty estimates are all clear. Here, the endpoint definition and timeframe are stated, but the main numerical result and analysis details are not reported. The reported safety counts can be read descriptively, with those limits in mind.

14. Why This Trial Matters Statistically

This study illustrates an important distinction in biostatistics: a safety study can document events among exposed participants without estimating a comparative treatment effect. The registry describes a single-group study, so the adverse-event counts answer a descriptive question about participants who received lubiprostone. They do not provide a like-for-like contrast with a control group.

The distinction between a participant count and an event count also matters. The primary outcome is defined as participants with at least one treatment-emergent adverse event. That measure does not reveal how many total events occurred, how often events recurred, or how long they lasted. The registry’s serious-event and other-event counts likewise describe affected participants, not a complete event history.

The record is also a useful example of why endpoint definitions and reported results need to be read together. It specifies when an event qualifies as treatment-emergent and gives a 25-week timeframe, yet the primary outcome’s numerical result is not reported. Without that result, readers cannot evaluate the stated primary safety question directly. The other safety counts add information but do not substitute for the missing primary result.

Finally, the registry’s design and analysis details set limits on inference. Open-label status, no comparator, no listed analyses, and unreported missing-data methods affect how much can be concluded from observed counts. The statistical value of the record lies in describing what was reported while keeping those limits distinct from claims of causation or comparative benefit.

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 main limitation is the absence of a control group. Because the study is single-group, the reported adverse-event counts cannot be contrasted with outcomes under another treatment or without the study intervention. The record therefore supports description of observed events, not a controlled estimate of treatment-associated risk.

The study is open-label, with masking recorded as none. The registry does not report whether event assessment was independently reviewed or whether any steps were taken to reduce the influence of unmasked reporting. It also does not describe how participants were selected or provide detailed baseline characteristics, so the representativeness of the enrolled group cannot be assessed from this record.

The primary outcome’s numerical result is not reported, despite its definition and timeframe being listed. No analysis entries are listed, and confidence intervals, hypothesis tests, missing-data methods, and the sample-size justification are not reported in the registry record. The record also does not provide event totals, participant-level detail, or enough information to determine overlap between serious and other adverse-event categories.

The study is described as 6-month, while the intervention description states treatment up to 24 weeks and the primary outcome timeframe is within 25 weeks. Those descriptions are recorded as stated; further details about actual follow-up duration or completion are not reported. These limitations constrain both the interpretation of safety counts and the ability to assess their precision or generalizability.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of the Safety of Lubiprostone in Pediatric Participants Aged ≥ 6 Years to < 18 Years With Functional Constipation — NCT02766777.
• Registry record last updated 2020-05-15; status last verified 2020-05.
• Results first posted 2020-05-15.
• 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

NCT02766777 is a completed phase 3, multicenter, open-label, single-group safety study of lubiprostone in pediatric participants with functional constipation. The registry lists 87 participants enrolled. Participants received 12 mcg or 24 mcg twice daily according to weight, for up to 24 weeks. The study began on 2016-04-12, and its primary completion date is 2016-11-04. Sucampo Pharma Americas, LLC is listed as sponsor.

The primary outcome is the number of participants with at least one treatment-emergent adverse event within 25 weeks. Its numerical result is not reported in the registry record. The adverse-event results list 2 participants with serious events and 24 with other adverse events, each among 87 at risk, and 0 deaths. No control group is listed, and the registry includes no analysis entries.