A Clinical Trial to Assess Three Different Doses of OPS-2071 in Patients With Bacterial Enteritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Trial to Assess Three Different Doses of OPS-2071 in Patients With Bacterial Enteritis (NCT02473393), a randomized phase 2 study. The primary outcome is Bacterial Elimination Rate (BER) in the CDI and EI Groups.

2. Clinical Question

3. Trial Design

This was a completed Phase 2, randomized, parallel-group trial of OPS-2071 in patients with bacterial enteritis. The registry lists an enrollment of 43 and identifies Otsuka Pharmaceutical Co., Ltd. as the sponsor. The study began on 2015-08-20, and primary completion was recorded as 2017-03-14. Masking was none, so the registry describes the trial as unmasked.

The trial’s brief summary states that it assessed safety, efficacy, and pharmacokinetics of multiple doses in patients with bacterial enteritis caused by CDI or enteric infection. The arm descriptions list OPS-2071 at 50 mg/day, 100 mg/day, 200 mg/day, and 400 mg/day, with tablets taken orally twice daily. The primary endpoint results posted for bacterial elimination are for a CDI group and EI groups at 50 mg, 100 mg, and 200 mg. A result for the 400 mg group is not reported in the registry record.

The primary endpoint was evaluated in the CDI group at screening, Day 4, and Day 11, the end of treatment. In the EI group, assessment was at screening, Day 4, and Day 8, the end of treatment. The reported primary endpoint is the bacterial elimination rate (BER), expressed as a percentage of participants, with a 95% confidence interval. The registry says the analysis was conducted by disease group and dose and describes assessments by causative strain and minimum inhibitory concentration; the posted result is for all strains total.

Randomization and parallel-group allocation describe key aspects of the design, but details such as the randomization procedure, allocation concealment, dose assignment process, and protocol-level statistical plan are not reported in the registry record. The registry lists secondary outcomes including recurrence of CDI, diarrhea resolution, stool frequency and characteristics, gastrointestinal symptoms, and clinical response rate.

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: Subjects with bacterial enteritis were divided into 2 groups, a Clostridium difficile infection (CDI) group for subjects with bacterial enteritis associated with C. difficile infection and an enteric infection (EI) group for subjects with bacterial enteritis for which the causative pathogen was Salmonella, Campylobacter, or pathogenic E. coli. Only one dosage (100 mg) of OPS-2071 was administered to CDI subjects and 3 dosages (100, 50, and 200 mg) were administered to EI subjects.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Microbiological per Protocol Set (MPPS) comprised those subjects in the FAS for whom the causative pathogen was identified and for whom microbiological outcome was assessed as "Excellent", "Good", or "Poor" , excluding subjects for whom microbiological outcome was assessed as "unknown/indeterminate".

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: Full Analysis Set (FAS): all subjects who had received the investigational medicinal product (IMP) at least once and from whom data on at least one efficacy endpoint had been obtained after the start of IMP administration.

6. Primary Endpoint

The registry lists the primary outcome as Bacterial Elimination Rate (BER) in the CDI and EI Groups, measured over CDI group: screening, Day 4 and Day 11 (end of treatment), EI group: screening, Day 4 and Day 8 (end of treatment).

The primary endpoint is the bacterial elimination rate, or BER: the proportion of causative strains assessed as either Excellent or Good. A strain assessed as Poor does not meet that endpoint definition. Strains with an outcome classified as unknown or indeterminate are excluded from the BER calculation. The registry states that the assessment followed criteria for the bacterial strain isolated as the causative pathogen, using microbiological examination data.

This endpoint is used to describe microbiological response, rather than symptoms alone. The registry specifies that results were considered by disease group and dose, and by minimum inhibitory concentration values for causative strains in the EI group. However, the posted primary results are for all strains total, rather than separate estimates for each named strain or MIC category. Consequently, these results describe the recorded microbiological outcome across the included strains and do not show how the outcome varied by organism or susceptibility measure.

The primary endpoint population was the Microbiological per Protocol Set. It included participants in the Full Analysis Set whose causative pathogen was identified and whose microbiological outcome was assessed as Excellent, Good, or Poor, with unknown or indeterminate outcomes excluded. The registry does not provide a full definition of the Full Analysis Set in the reported record.

In general, a proportion gives a concise description of how often a defined outcome occurred in an analysis population. It does not, by itself, establish that treatment caused the outcome. A confidence interval adds information about the uncertainty around the estimated proportion, which is especially important when the endpoint population is small.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary outcome at the level defined by the registry: a causative strain is classified as meeting the BER definition if its assessment is Excellent or Good. The registry reports the result as a percentage and supplies a 95% confidence interval. For a binary endpoint, the estimated proportion is based on the number meeting the definition relative to the endpoint analysis population. The registry does not provide the underlying counts for each outcome category, so those counts should not be inferred from the percentages.

What does the confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimate under a specified statistical procedure. It is not a range in which every individual participant’s outcome lies, and it is not a guarantee that the true value is inside the interval. Its width depends on the amount of information in the data and the method used to construct it. Here, the reported intervals are broad, which means the point estimates should be read with caution rather than as highly precise values.

The registry identifies the interval as a 95% confidence interval but does not state the interval construction method in the record. Different methods can behave differently for binary proportions, particularly with small samples or estimates close to 0% or 100%. Because the method is not reported, the intervals should be interpreted as posted rather than reverse-engineered or replaced with a different calculation.

Why does the analysis population matter?

The BER analysis uses the Microbiological per Protocol Set. The registry defines this as participants in the Full Analysis Set for whom the causative pathogen was identified and for whom microbiological outcome was assessed as Excellent, Good, or Poor, excluding unknown or indeterminate outcomes. The definition makes the endpoint population narrower than the full enrolled population: participants without an identified causative pathogen or with an unknown or indeterminate microbiological result do not contribute to the stated BER calculation. The complete definition of the Full Analysis Set is not reported in the registry record.

This population choice has interpretive consequences. The estimate describes the eligible microbiologically assessed population, rather than necessarily describing every randomized or enrolled participant. Excluding unknown or indeterminate outcomes may be reasonable for a microbiological endpoint, but it also means the rate does not summarize those unclassified cases. The registry does not report a sensitivity analysis showing how alternative handling of those outcomes would affect the result.

Why can’t the groups be treated as a direct comparison?

The trial is described as randomized and parallel-group, but the primary results are presented as separate percentages and confidence intervals for the CDI group and EI dose groups. A treatment comparison normally requires an explicitly defined contrast, such as a difference between two groups, together with an estimate of uncertainty and an appropriate analysis. Such contrasts and tests are not reported for BER. In addition, CDI and EI are different disease groups, so their separate BER values should not be treated as if they were randomized treatment arms within a single common population.

In general, randomization can support causal comparisons when the relevant groups, outcomes, and analysis are specified and the comparison is reported. It does not turn every difference between displayed group estimates into a treatment effect. The registry record does not give enough detail to assess the randomization procedure or the statistical model, and the posted endpoint results do not present an adjusted dose comparison.

What does the endpoint definition imply?

The registry counts assessments of Excellent or Good as elimination and excludes unknown or indeterminate results. It also describes assessments of Poor, which are part of the stated endpoint population but do not meet the BER definition. This classification determines what the reported proportion represents. It is not a continuous measure of bacterial quantity, and it is not the same as the clinical response rate or the symptom-based outcomes listed as secondary outcomes.

The registry describes analyses by disease group and dose and by MIC values for causative strains, with named organisms listed for the EI group. It then states that the data were shown as all strains total. The reported estimates therefore do not allow readers to assess organism-specific BER or variation across MIC categories. Such subgroup-specific values are not reported in the registry record.

How should planning calculations be read?

In general, a sample-size calculation estimates how many participants may be needed to detect a specified effect under chosen assumptions. The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event calculations, the stated basis is the total number of events; other calculations are expressed as participants per arm.

These are planning illustrations based on the observed effect, not the trial’s own design justification and not observed power. They do not show that the trial was designed around those assumptions. The registry does not report the original sample-size rationale, and no specific planning values are included in the endpoint details. General sample-size calculations depend on assumptions about the target effect and analysis; they should not be interpreted as evidence that an observed result is reliable or that a study had a particular probability of detecting an effect after completion.

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("CDI Group", "EI Group (50 mg)", "EI Group (100 mg)", "EI Group (200 mg)")
n      <- c(2, 9, 9, 7)
events <- c(2, 7, 8, 6)
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  CDI Group  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  EI Group (50 mg)  9  7  77.8  40.0  97.2  45.3  93.7  44.4  93.3
ARM  EI Group (100 mg)  9  8  88.9  51.8  99.7  56.5  98.0  55.5  97.5
ARM  EI Group (200 mg)  7  6  85.7  42.1  99.6  48.7  97.4  47.3  96.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six secondary outcomes, covering CDI recurrence, time to diarrhea resolution, stool frequency and characteristics, abdominal pain, nausea and vomiting, and clinical response rate. It also reports nine outcome measures in total. The record does not describe a strategy for controlling multiplicity across the primary and secondary outcomes, or across the disease, dose, strain, and MIC analyses described for microbiological outcomes. No adjustment method or hierarchy of testing is reported in the registry record. In general, when many outcomes or subgroup analyses are examined, the chance of finding an apparently notable result by chance can increase; an analysis plan is needed to clarify how such findings should be interpreted.

The registry record contains no reported analysis entries. It therefore does not provide further analysis specifications such as model details, covariate adjustment, or planned contrasts. A complete statistical analysis plan is not reported, and whether interim analyses were conducted is not reported in the registry record. The record also does not provide a sample-size justification.

For the primary endpoint, unknown or indeterminate microbiological outcomes are excluded from the defined Microbiological per Protocol Set. The handling of other missing data, including missing assessments at the scheduled visits, is not reported. The record does not explain how participants without an identified causative pathogen were handled outside the endpoint-set definition, nor does it report imputation or sensitivity analyses for missing outcomes. The Full Analysis Set is referenced in the Microbiological per Protocol Set definition, but its complete definition is not reported.

These gaps do not change the posted estimates, but they limit assessment of whether the analysis followed a prespecified plan and how robust the results would be under alternative assumptions about missing data or multiple testing.

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: pyrexia (7.7%).

The registry reports serious adverse events using a number at risk and a number affected for each group. In the CDI group, 0 of 5 participants at risk were reported as affected by a serious adverse event. In the EI 50 mg group, the corresponding count was 0 of 12; in the EI 100 mg group, it was 1 of 13; and in the EI 200 mg group, it was 0 of 12. Deaths were reported as 0 in each group.

The registry also identifies Pyrexia at 7.7% as a top serious-event term. The record does not state which group that term is associated with in the information, so it should not be assigned to a particular dose group. Serious-event counts and event terms are different summaries: a count describes how many participants were affected, while a term names an event recorded in the safety data.

In general, small group counts make safety estimates imprecise and may not reveal uncommon events. These figures describe what was reported during the study; they do not establish that an event was caused by OPS-2071 or that no unreported or rare event occurred. The registry’s other adverse-event counts are not the same as serious adverse-event counts.

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

The primary endpoint results show the reported proportions of assessed causative strains classified as Excellent or Good in the listed groups. They also show substantial uncertainty around those estimates, as reflected in the 95% confidence intervals. The CDI estimate is based on 2 participants, and the EI estimates are based on groups of 9, 9, and 7 participants. The intervals are broad, so the point estimates should not be treated as precise descriptions of the underlying rates.

The results do not establish that one dose produces a higher BER than another. No direct dose contrasts or statistical tests for the primary endpoint are reported. The CDI result is from a different disease group and should not be compared with EI dose groups as though it were another dose arm. The 400 mg/day regimen is described in the registry, but its BER result is not reported in the registry record.

These data also do not establish that OPS-2071 caused the observed microbiological outcomes. The record describes randomization, but the posted endpoint results are group-level rates rather than a reported comparison against a control or between randomized dose groups. No placebo or untreated-group BER result appears among the reported primary endpoint results. A within-group proportion answers how often the outcome was recorded in that group; it does not by itself estimate what would have happened to the same participants under another regimen.

The primary endpoint is microbiological and uses a specific assessment definition. It should not be conflated with symptom resolution, stool frequency, clinical response, or recurrence of CDI, which are separately listed outcomes. Results for those secondary outcomes are not included in the endpoint details. Nor do the BER estimates provide a complete account of safety or pharmacokinetics.

Accordingly, the posted results are best read as descriptive, exploratory evidence from a small analysis population. They can inform how the registry characterized microbiological outcomes, but they do not support a definitive comparative or causal conclusion. The missing analysis details, absent direct contrasts, and limited endpoint group sizes are central to that interpretation.

14. Why This Trial Matters Statistically

This trial illustrates why an estimated percentage should be read together with its analysis population, confidence interval, and design. A point estimate can look high while remaining uncertain when only a small number of participants contribute. The CDI BER is 100%, but its 95% confidence interval extends from 15.8% to 100%. That interval is a reminder that an observed boundary value does not automatically imply a precise estimate.

The registry also demonstrates that results can be organized around more than one clinical dimension. The trial included CDI and EI populations, and the stated microbiological assessment considered dose, causative strain, and MIC. Yet the posted primary estimates are all-strains totals, so they do not answer whether BER varied by organism or MIC. Statistical reporting needs to make clear which comparisons and subgroups are actually represented by the displayed estimates.

Another important distinction is between a trial’s randomized design and the analyses that are reported. Random allocation is relevant to comparative inference, but the BER results are presented as group-specific proportions without direct dose contrasts. Readers should not treat the ordering of those proportions as a formal dose comparison. Reporting estimates and uncertainty for prespecified contrasts would be necessary to address comparative questions directly.

Finally, the registry’s limited analysis detail matters for reproducibility and interpretation. The record does not report the analysis plan, multiplicity strategy, sample-size justification, or handling of missing assessments beyond excluding unknown or indeterminate microbiological outcomes from the endpoint population. These are not merely technical details: they help readers judge how planned the analysis was and how sensitive the conclusions may be to analytic choices. The trial is therefore a useful example of separating descriptive endpoint results from stronger claims that require additional reported evidence.

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 primary endpoint estimates come from small analysis groups, and the confidence intervals are broad. The CDI estimate is based on 2 participants; EI group estimates are based on 9, 9, and 7 participants. These group sizes limit precision and make it difficult to distinguish an underlying difference from sampling variation. The registry’s overall enrollment of 43 does not change the smaller endpoint denominators.

The reported BER results are not a complete presentation of every regimen described in the trial. The arm descriptions include OPS-2071 400 mg/day, but no BER estimate for that regimen is reported in the registry record. The results are also presented for all strains total, even though the registry describes analyses by causative strain and MIC. Organism-specific and MIC-specific endpoint estimates are not reported in the registry record.

The record gives no direct dose comparison, no comparison with a placebo or untreated group, and no statistical test for the posted BER estimates. It does not report the confidence-interval construction method, the detailed randomization procedure, or the complete statistical analysis plan. The sample-size justification and whether interim analyses were conducted are also not reported in the registry record.

The endpoint population excludes unknown or indeterminate microbiological outcomes and is defined through the Full Analysis Set, whose full definition is not reported. Missing assessment handling and sensitivity analyses are not reported. A multiplicity strategy for the multiple outcomes and described subgroup analyses is also not reported. These limitations restrict how far the estimates can be generalized and prevent firm comparative interpretations from the posted results alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Clinical Trial to Assess Three Different Doses of OPS-2071 in Patients With Bacterial Enteritis — NCT02473393.
• Registry record last updated 2021-03-24; status last verified 2021-03.
• Results first posted 2021-03-24.
• 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 record describes a completed, randomized, unmasked, parallel-group Phase 2 trial of OPS-2071 in bacterial enteritis associated with CDI or enteric infection. It lists enrollment of 43 and identifies Otsuka Pharmaceutical Co., Ltd. as sponsor. The primary endpoint is bacterial elimination rate, defined by microbiological assessments of causative strains classified as Excellent or Good, with results reported as percentages and 95% confidence intervals.

Posted BER results include a CDI group and EI groups at 50 mg, 100 mg, and 200 mg. The registry describes a 400 mg/day regimen, but a BER result for that group is not reported in the registry record. The estimates are group-specific and do not include direct dose comparisons. Secondary outcomes are listed, but detailed analysis methods, missing-data handling, multiplicity procedures, and sample-size justification are not reported.