Evaluation of the Bioequivalence of Sprinkle and Capsule Formulations of Lubiprostone, as Compared to Placebo: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Bioequivalence of Sprinkle and Capsule Formulations of Lubiprostone, as Compared to Placebo (NCT03097861), a randomized phase 3 study. The primary outcome is Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week.

2. Clinical Question

The study was designed to evaluate the bioequivalence of the sprinkle and capsule formulations while also including a placebo group. These are related but distinct questions: comparing the active formulations addresses their similarity, whereas comparisons with placebo provide a separate reference. The registry record does not report the numerical primary outcome results, a direct estimate comparing the active formulations, or a criterion for deciding whether bioequivalence was established. Therefore, the clinical question can be described from the study design, but the posted record does not permit a quantitative answer.

3. Trial Design

This was a randomized, placebo-controlled, double-blinded, multicenter, parallel-group Phase 3 study. The registry record labels masking as quadruple. It does not identify which roles were masked or give further details about how masking was implemented. Random allocation assigns participants to study groups by chance; in general, this can reduce systematic differences between groups at entry, though it does not guarantee that every characteristic will be balanced.

The listed groups were lubiprostone sprinkle, lubiprostone capsule, and placebo. Each active formulation was described as 24 mcg twice daily for 7 days; placebo matching either formulation was also given twice daily for 7 days. The overall enrollment was 552. That enrollment figure should not be treated as the number analyzed for the primary endpoint: the primary outcome population is listed as per protocol, and its analyzed group sizes are not reported in the registry record.

The study start date was 2017-03-13, and primary completion was recorded as 2017-08-17. Its status is completed. These dates describe the conduct recorded in the registry and do not add information about the timing of individual participants’ treatment or follow-up beyond the stated 1-week treatment period. The record identifies chronic idiopathic constipation as the condition under study and states that the formulations were administered orally.

The registry record does not report the allocation ratio, the methods used to generate or conceal the random sequence, the locations of participating centers, or details of eligibility criteria beyond the adult population with chronic idiopathic constipation. It also does not state whether participants could switch formulations or describe adherence procedures. Such details should not be inferred from the parallel-group label or the stated treatment schedules.

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: Actual randomization ratio of sprinkle:placebo:capsule (2:1:1) was different than the planned randomization ratio (1:1:1)

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol 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: Per Protocol Population

6. Primary Endpoint

The registry lists the primary outcome as Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week, measured over during the 1-week treatment period.

The primary endpoint was the observed spontaneous bowel movement (SBM) count within 1 week, expressed as SBMs per week. The registry describes it as a mean, with standard deviation as the dispersion measure, during the 1-week treatment period. Counts were based on observed data recorded in an electronic daily diary and represented the actual number of SBMs during that period. The specified analysis population was the per protocol population.

A bowel-movement count is a continuous outcome for the stated analysis because the group result is summarized as a mean, even though each individual count is discrete. A group mean gives an average count over the defined period; a standard deviation describes variation among individual observations around that average. In general, this type of endpoint can make a treatment-group comparison easier to interpret than a collection of diary entries, while the distribution and completeness of the underlying observations still matter.

The registry record does not report the group means, standard deviations, or a treatment-effect estimate for this endpoint. It also does not give a clinical threshold for interpreting a difference in SBM counts. Consequently, the endpoint’s measurement and intended analysis can be described, but its observed magnitude and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean describe?

The primary outcome is a mean count of spontaneous bowel movements per week. A mean is the sum of the observed values divided by the number of observations included in the calculation; no new calculation is made. It describes the group’s average, not the experience of every participant. The registry specifies standard deviation as the measure of dispersion. In general, standard deviation describes how spread out observations are around the mean. A larger standard deviation indicates more variability in the observations, while a smaller one indicates observations that are more tightly grouped.

The outcome uses observed entries from an electronic daily diary during the 1-week treatment period. Diary-based measurement can capture repeated observations over the stated period, but completeness and consistency of recording can affect what is available for analysis. The registry record does not describe rules for incomplete diary entries, data checks, or how a participant with partial records contributed to the endpoint. Those procedures are therefore not reported in the registry record.

What does randomization contribute?

Randomization is a method for assigning participants to treatment groups by chance. In general, it helps prevent deliberate or systematic assignment based on participant characteristics and supports comparisons between groups. It does not ensure that groups will be identical in every measured or unmeasured characteristic, and it does not by itself address missing outcomes, adherence, or analysis choices. The record identifies the trial as randomized but does not describe sequence generation, allocation concealment, or the allocation ratio.

The parallel-group design means that the listed groups are separate treatment groups rather than a sequence in which each participant receives every formulation. The record describes a placebo-controlled, double-blinded study and labels masking as quadruple. It does not specify which people were masked, or describe the procedures used to maintain masking. These labels are design information, not results about the success of masking.

Why is the analysis population important?

The primary endpoint is identified for the per protocol population. This means the registry ties the endpoint to a defined analysis population rather than stating that every randomized participant was included. The exact protocol adherence rules, exclusions, and analyzed group sizes are not reported in the registry record. Without those details, it is not possible to determine how the analyzed population relates to the 552 participants enrolled in the study or whether exclusions differed across groups.

In general, analysis choices can affect a treatment estimate. Excluding participants after randomization may reduce the protection against group differences that random allocation is intended to support, depending on who is excluded and why. This is a general methodological consideration, not a claim that any particular bias occurred in this trial. The record does not provide enough detail to assess that possibility.

How should uncertainty be understood?

In general, a confidence interval gives a range of estimates compatible with the observed data under the method’s assumptions, and it communicates uncertainty about an estimated effect. A p-value addresses how unusual data at least as extreme as those observed would be under a specified null model; it does not measure the probability that a treatment works or establish clinical importance. Neither a confidence interval nor a p-value for the primary outcome is reported in the registry record. The standard deviations needed to describe observed variability are also not reported.

The record’s sample-size assumptions describe planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They state that the effect to detect is a specified fraction of the observed effect. Those statements describe the assumptions used for the illustrations, not the trial’s own design justification. No illustration values or primary outcome effect are reported in the registry record, so their numerical implications cannot be assessed. Planning sample sizes are not observed power and should not be presented as evidence about the trial’s achieved result.

What limits a bioequivalence interpretation?

Bioequivalence is the stated purpose for comparing the sprinkle and capsule formulations. In general, a formal bioequivalence analysis requires a defined comparison and a prespecified range within which differences are considered compatible with equivalence. The registry record does not report the equivalence criterion, the estimate for the direct formulation contrast, or its uncertainty. It also does not specify in the available outcome description how the SBM count is linked to a formal bioequivalence decision. The stated study purpose alone cannot substitute for these analytical details.

10. Multiplicity, Missing Data and Analysis Populations

The record lists four outcome measures and two analyses. It identifies observed SBM count within 1 week as the primary outcome and lists mean SBM consistency score, mean SBM straining score, and treatment-emergent adverse events among the secondary outcomes. The primary endpoint is also flagged as having several categories or time points, and the record does not reduce it to one comparison. The specific categories, time points, and contrasts are not reported in the registry record.

When several outcomes, time points, or comparisons are examined, the chance of finding at least one apparently unusual result can increase. In general, multiplicity procedures can address this by adjusting how results are interpreted or tested. The registry record does not report a multiplicity adjustment, a hierarchy of tests, or which of the two listed analyses addressed which outcome. It would therefore be inappropriate to assume that all comparisons were prespecified or controlled as a single family.

Missing-data handling is not reported in the registry record. The primary measure relies on observed electronic diary data, but the record does not state how incomplete diaries, missed entries, or participants with no usable outcome data were handled. It also does not describe imputation, sensitivity analyses, or assumptions about missingness.

The primary outcome is assigned to the per protocol population. The record does not define that population or report its size by group. Other analysis populations, including whether an intention-to-treat analysis was conducted, are not reported in the registry record. These gaps limit assessment of how participant exclusions and missing observations may have influenced the endpoint analysis.

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 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists serious adverse event counts by group. The placebo group had 0 serious adverse events among 143 participants at risk; the lubiprostone sprinkle group had 0 among 275 at risk; and the lubiprostone capsule group had 0 among 130 at risk. Deaths were recorded as 0 in each group. No serious adverse event terms are listed.

The record also reports other adverse event counts: 15 for placebo, 50 for lubiprostone sprinkle, and 29 for lubiprostone capsule. These figures should be read as the posted counts, not as calculated percentages or as comparisons adjusted for time at risk. The record does not give event descriptions, severity, relationship to treatment, timing, or whether an individual could contribute more than one event. It also does not report uncertainty intervals for these safety counts.

Zero reported serious events in the listed groups means none were recorded in those group entries; it does not establish that the true risk is zero. The groups differ in their reported numbers at risk, and a small or absent event count cannot by itself establish that the groups have equivalent safety. These figures are descriptive registry data, not a complete safety assessment.

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

The registry record describes a randomized comparison of lubiprostone sprinkle, lubiprostone capsule, and placebo, with observed SBM count during a 1-week treatment period as the primary endpoint. It also gives the dose schedules, the primary analysis population label, and adverse event counts. These details identify the question the study was intended to address and the way the primary measure was characterized.

However, the numerical primary outcome results are not reported in the registry record. Without group means, variability, an estimated contrast, or a confidence interval, the record does not show the magnitude or precision of the observed SBM results. It therefore does not support a conclusion about the direction or size of any difference between the treatment groups, nor a quantitative judgment about similarity of the two formulations.

The study’s bioequivalence objective should be distinguished from evidence that bioequivalence was demonstrated. The record does not state an equivalence margin or provide a formal estimate and uncertainty interval for the sprinkle-versus-capsule comparison. The study purpose, by itself, is not an outcome.

The safety counts indicate that no serious adverse events and no deaths were listed in the three groups, while other adverse event counts were also reported. These counts do not establish that there were no risks, that the groups have the same safety profile, or that any particular event was caused by treatment. The record does not supply the event detail or statistical uncertainty required for those interpretations.

In general, trial results are most informative when the endpoint definition, analyzed population, treatment contrast, estimate, and uncertainty are all available together. The registry record contains some design and endpoint information but not the primary numerical results or several key analysis details. Accordingly, conclusions should be limited to describing what was registered rather than inferring an effect or a formal equivalence finding.

13. Why This Trial Matters Statistically

This study raises a statistical question that is not answered simply by comparing the names of two formulations. A claim of bioequivalence depends on a direct comparison between formulations and on how much difference is considered acceptable. The registry record states the objective but does not report the comparison estimate, uncertainty, or an equivalence criterion. That distinction is important when reading any study whose stated purpose includes equivalence.

The primary endpoint also illustrates the need to distinguish measurement from inference. The record defines a mean count based on observed electronic diary entries and identifies the analysis population and time frame. Those details help clarify what the endpoint represents. But an endpoint definition does not reveal the observed group results. Without the means and their variability, readers cannot judge how large or precise a difference was.

The trial also lists several outcomes and more than one analysis. In general, multiple outcomes, time points, and comparisons create interpretive challenges because results can vary across choices of endpoint and contrast. Information about prespecification and multiplicity handling helps readers understand how much weight to place on individual findings. Those procedures are not reported in the registry record.

Finally, the listed safety counts show why descriptive event data need careful context. Counts can be useful for identifying what was recorded, but they do not alone quantify comparative risk or establish the absence of risk. The registry record’s combination of design information, endpoint definitions, and safety counts is informative, while its missing primary effect estimates and analysis details leave the central statistical conclusions unresolved.

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 main limitation for interpreting efficacy is that the registry record does not report numerical primary outcome results. Group means, standard deviations, comparative estimates, confidence intervals, and p-values are not reported. Consequently, the effect’s direction, size, and precision cannot be assessed from the record.

The primary endpoint is specified for the per protocol population, but the record does not define protocol adherence, state analyzed group sizes, or explain post-randomization exclusions. The overall enrollment of 552 does not establish how many participants contributed to the primary analysis. Missing-data handling for the electronic diary outcome is also not reported.

The stated bioequivalence objective is not accompanied in the registry record by an equivalence margin or the results of a direct formulation comparison. Without those items, the objective cannot be translated into a formal conclusion. The record also flags multiple categories or time points for the primary outcome but does not identify them or explain how comparisons were selected.

Multiplicity procedures, the detailed statistical plan, sample-size justification for the trial, and interim analyses are not reported in the registry record. The record’s planning assumptions describe illustrations, not the trial’s own design rationale, and no illustration results are available for interpretation.

Safety information is limited to counts of serious and other adverse events and deaths. Event descriptions, severity, relatedness, timing, and uncertainty are not reported. Further design details—including eligibility criteria beyond adults with chronic idiopathic constipation, allocation procedures, and which roles were masked—are also not reported. These limitations restrict conclusions to the registered design and descriptive counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of the Bioequivalence of Sprinkle and Capsule Formulations of Lubiprostone, as Compared to Placebo — NCT03097861.
• Registry record last updated 2020-01-14; status last verified 2020-01.
• Results first posted 2020-01-14.
• 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

NCT03097861 is a completed randomized, placebo-controlled, double-blinded, multicenter, parallel-group Phase 3 study of lubiprostone sprinkle and capsule formulations versus placebo in adults with chronic idiopathic constipation. The record describes each active formulation as 24 mcg twice daily for 7 days and placebo matching a formulation on the same schedule. Enrollment was 552.

The primary endpoint was observed SBM count during the 1-week treatment period, summarized as a mean with standard deviation, in the per protocol population. Numerical primary results and formal bioequivalence criteria are not reported in the registry record. The record lists four outcome measures and two analyses. It reports no serious adverse events or deaths in the listed groups, along with counts for other adverse events.