Safety, Tolerability and the Pharmacokinetics of Ridinilazole in Adolescent Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and the Pharmacokinetics of Ridinilazole in Adolescent Subjects (NCT04802837), a randomized phase 3 study. The primary outcome is Incidence and Severity of Treatment-emergant Adverse Events.

2. Clinical Question

The record describes a Phase 3, randomized, parallel-group, active-controlled study. Its official title identifies safety, tolerability, and pharmacokinetics as the study aims. The intervention schedules use matching placebos to maintain the blind, and masking is listed as quadruple. Which people or roles were masked is not reported in the registry record.

The clinical question is therefore principally about describing safety in a very small adolescent study, rather than establishing a precise difference between treatments. The record reports one participant in each arm. The posted primary outcome values are zero in both arms, but the record states that no analysis was done because enrollment did not reach the target number needed before termination and was insufficient to produce statistically reliable results. These observations cannot characterize treatment effects across a broader adolescent population.

3. Trial Design

This was a Phase 3, randomized, active-controlled, parallel-group study of ridinilazole compared with vancomycin in adolescent subjects with Clostridioides difficile infection. Randomized allocation is listed in the registry. The study is also described as quadruple-masked. In the ridinilazole arm, participants received ridinilazole BID and comparator placebo QID; in the vancomycin arm, participants received vancomycin QID and ridinilazole placebo BID. The stated purpose of the differing placebo schedules was to maintain the blind. Each regimen is described as 40 doses over 10 days. Dose amounts are not reported in the registry record.

The study record lists enrollment of 2, with one participant in the ridinilazole arm and one in the vancomycin arm. It lists a start date of 2021-05-19 and a primary completion date of 2021-09-17. The overall status is terminated. The reason for termination, the planned target enrollment, and the date of termination are not reported in the registry record. The registry states that enrollment did not reach the target number of subjects needed before study termination.

Safety was to be assessed until study completion (Day 100), using CTCAE v4. The registry’s stated primary outcome is incidence and severity of treatment-emergent adverse events. The official title also identifies pharmacokinetics as an aim, but a posted primary pharmacokinetic measure is not reported in the registry record. The record lists one outcome measure and no posted analyses. Details of the randomization procedure, allocation concealment, masking roles, protocol deviations, and analysis populations are not reported in the registry record.

This design would ordinarily permit a comparison of outcomes between assigned groups. With one participant per arm and no reported outcome analysis, however, the record does not support a reliable estimate of the difference between treatment groups. The parallel-group structure and randomized assignment describe how the study was organized; they do not overcome the limited information in the final posted results.

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

Analysis population for the primary outcome, as defined in the registry: No analysis was done for study outcome measures due to the fact that enrollment in the clinical trial did not reach the target number of subjects needed prior to study termination and was insufficient to produce statistically reliable results.

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 Incidence and Severity of Treatment-emergant Adverse Events, measured over Until study completion (Day 100).

The primary endpoint is titled “Incidence and Severity of Treatment-emergant Adverse Events.” It is expressed as a count of participants, and the registry describes safety assessment using CTCAE v4. The observation period is listed as until study completion (Day 100). The record does not explain how the endpoint’s severity categories were combined or how the incidence was operationally defined beyond its title and description.

In general, adverse-event endpoints are used to describe harms observed during a defined period of treatment and follow-up. Counting participants with events provides a direct way to report how many people experienced an event; grading severity distinguishes events by their clinical severity classification. This endpoint can therefore support a descriptive safety account. A count alone does not show how often events occurred within a participant, and the posted record does not provide event-level details for this primary outcome.

The posted arm values are zero participants for ridinilazole and zero for vancomycin, with one participant in each arm. The record explicitly says no analysis was done because enrollment was insufficient to produce statistically reliable results. Accordingly, the zero counts describe only the participants recorded in this trial. They do not establish that events would not occur in a larger group, and they do not quantify a comparative safety difference. How missing or incomplete safety observations were handled is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group study with an active comparator and quadruple masking. The statistical results, however, are descriptive counts only: one participant is listed in each treatment arm, and the primary outcome value is zero in each. No analysis is reported. The distinctions below explain what these kinds of methods can and cannot establish in general, and how the registry record applies to this trial.

What does randomization contribute?

In general, randomization assigns participants to treatment groups by chance. When implemented as planned, it can reduce systematic differences between groups at the point of assignment. It does not guarantee that small groups will have similar characteristics, and it cannot ensure a precise treatment comparison when very few participants are enrolled. The record states that allocation was randomized, but the randomization sequence method and allocation concealment are not reported in the registry record. With one participant per arm, the posted results cannot show whether randomization achieved balance on participant characteristics.

What does masking contribute?

Masking is intended to limit the influence of knowledge about assigned treatment on participant experience, care, or outcome assessment. The record lists quadruple masking and describes matched placebo schedules for the ridinilazole and vancomycin arms. It does not identify which roles were masked, explain how the blind was maintained in practice, or report whether masking was assessed. General principles about masking therefore describe its intended function, not evidence that any particular bias was prevented in this trial.

What can a count endpoint tell us?

The primary measure is a count of participants with treatment-emergent adverse events, with severity assessed using CTCAE v4. A count communicates how many participants had an event in the recorded group. In general, event counts may be summarized as proportions when the number at risk is known, but a proportion based on a very small group has substantial uncertainty. No new proportion or comparison is needed to interpret this record: the registry itself reports the counts and group sizes. It gives no confidence interval or other uncertainty interval for the endpoint.

Severity is part of the endpoint’s title, but the record does not post a severity breakdown for the primary outcome. It also does not report event-level details or explain the rules used to count multiple events in one participant. The posted value of zero is therefore best read as the recorded count of participants with the endpoint, rather than as a detailed description of every safety observation.

Why is there no inferential comparison?

In general, an inferential comparison uses a statistical model or test to assess the treatment-group contrast while accounting for uncertainty. A confidence interval describes a range of values compatible with the data and model assumptions; a narrow interval indicates greater precision than a wide one. A p-value, when used, describes how incompatible the data are with a specified null hypothesis under the test assumptions. Neither measure by itself establishes clinical importance. The registry reports no such analysis for this outcome, and no comparison should be inferred from the two arm counts.

For binary outcomes, estimates and tests rely on the number of participants with and without events in each group. With one participant per arm and zero posted events in both, a two-arm comparison is not estimable using the stated approach. The record’s analysis note says no study outcome analysis was done because enrollment did not reach the target needed before termination and was insufficient to produce statistically reliable results. This is why the zero counts should not be converted into a claim of equal outcomes.

What does a planning calculation mean?

In general, sample-size planning asks how many participants would be needed to detect a specified effect under chosen assumptions, such as a significance level, allocation, and statistical approximation. A calculation based on an observed effect is an illustration, not the original trial’s design justification and not evidence of “observed power.” Planning values depend on assumptions about the effect to detect and the analysis method. The registry record does not report the target enrollment number, the original sample-size justification, or a complete statistical analysis plan. No numeric planning result is available in the registry record for interpretation.

The record’s planning description refers to a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. Those are general planning assumptions described in the record, not a report of the trial’s own design rationale. Since no reliable observed treatment effect was estimated, such planning illustrations cannot substitute for an analysis of this trial.

How should the design and results be separated?

The randomized and masked design describes intended methods. The outcome counts describe what was posted after enrollment. These are distinct kinds of evidence: design strengths do not create information that was not collected, and a small set of observations cannot yield a stable estimate merely because assignment was randomized. No analysis populations, handling of missing outcome data, prespecified test, adjustment method, or interim-analysis plan are reported in the registry record. The statistical interpretation should therefore remain descriptive and limited to the posted counts.

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("Ridinilazole", "Vancomycin")
n      <- c(1, 1)
events <- c(0, 0)
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  Ridinilazole  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Vancomycin  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when several outcomes, time points, subgroups, or statistical comparisons are tested. In general, conducting many tests can increase the chance of at least one apparently notable result by chance, so an analysis plan may specify which outcomes are primary and how testing will be handled. The registry lists one outcome measure and no posted secondary outcomes. It reports no analyses, so there are no posted hypothesis tests or multiplicity adjustments to interpret. Whether additional outcomes or planned comparisons were specified elsewhere is not reported in the registry record.

The registry identifies the primary safety outcome and gives an assessment period through study completion (Day 100). A complete statistical analysis plan, including the planned definition of analysis populations, model choices, covariates, subgroup analyses, or multiplicity procedure, is not reported in the registry record. The record says the outcome measures were not analyzed because enrollment did not reach the target needed before termination and was insufficient for statistically reliable results.

Missing-data handling is also not reported in the registry record. The record does not describe completeness of follow-up, withdrawals, exclusions, or how incomplete safety observations would have been treated in an analysis. The posted counts identify one participant at risk in each arm, but those counts alone do not establish how much follow-up information was available for every planned assessment. It would be inappropriate to assume that all scheduled observations were complete or that missing information was absent.

Analysis-population definitions, such as whether participants were analyzed according to assignment or treatment received, are not reported in the registry record. No statistical model or population-specific analysis is posted. These omissions matter because they limit reproducibility and prevent readers from determining precisely which participants and observations would have contributed to a planned inferential result. Given the absence of an analysis, multiplicity and missing-data procedures cannot be evaluated from the posted results.

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 0% reporting threshold.

The safety group for ridinilazole lists one participant at risk, zero with a serious adverse event, zero with another adverse event, and zero deaths. The vancomycin group likewise lists one participant at risk, zero with a serious adverse event, zero with another adverse event, and zero deaths. No top serious adverse-event terms are listed.

These entries are counts, not estimates of event probability or comparative risk. In general, a zero count in a small group means that no event was recorded among the participants counted; it does not establish that the event cannot occur or that the treatment groups have the same safety profile. The registry does not post a statistical comparison or uncertainty interval for these safety figures. It also does not provide event-level descriptions or details about missing safety observations.

The serious adverse-event counts should be interpreted separately from the primary endpoint’s broader title, which refers to incidence and severity of treatment-emergent adverse events. The posted safety figures report no serious events, other events, or deaths in either group, but the registry states that no outcome analysis was done because enrollment was insufficient to produce statistically reliable results. These small counts describe the record; they do not support a general conclusion about safety.

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

The results have a limited descriptive meaning. The registry records one participant in each arm, with zero participants reported for the primary safety outcome in each. It also lists zero serious adverse events, zero other adverse events, and zero deaths in each one-person safety group. These registry entries describe the posted observations from this trial.

They do not establish that ridinilazole and vancomycin have the same incidence or severity of adverse events. A lack of events in such small groups does not show that events would remain absent if more participants were observed. Nor does the record estimate a treatment difference with a confidence interval, provide a p-value, or report an analysis that could quantify uncertainty. The registry explicitly states that no analysis was done because the trial did not enroll the target number needed before termination and enrollment was insufficient to produce statistically reliable results.

The record also cannot establish a broad safety profile for adolescents with Clostridioides difficile infection. It does not report enough participant characteristics to assess how representative the enrolled participants were, and it does not post a pharmacokinetic result despite the study’s stated pharmacokinetic aim. Detailed information on missing observations and analysis populations is not reported in the registry record.

In general, a randomized, masked study can be designed to support a comparison, but the amount and quality of outcome information still determine how informative its results are. Here, randomization and masking describe the planned design, while the very small enrollment and absence of inferential analyses constrain the conclusions. The appropriate interpretation is not that one treatment is preferable, inferior, or equivalent. It is that the registry reports no primary safety events among the two enrolled participants and does not provide statistically reliable comparative results.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between a study’s intended design and the information available from its final posted results. Randomized allocation, active control, parallel groups, and quadruple masking are design features aimed at producing a structured treatment comparison. The registry nevertheless reports only one participant per arm and no analysis of the primary outcome. Design features cannot replace the outcome information that a larger enrollment might have produced.

The example also shows why counts need context. A zero count may appear reassuring when read without the group size, follow-up period, or analysis status. Here, the group size is one in each arm, safety follow-up is described through Day 100, and the record says outcome analyses were not performed because enrollment was insufficient for statistically reliable results. The counts are useful as a transparent record of what was posted, but they do not determine the frequency of events in a broader population or establish a comparative treatment effect.

For clinical researchers, the registry entry emphasizes the value of clear reporting when a trial terminates before reaching its intended enrollment. The reason for termination and target enrollment are not reported in the registry record, and no detailed analysis plan or missing-data procedure is available. Those gaps limit readers’ ability to evaluate the original design choices and the status of planned outcomes.

Statistically, the record is most useful as an example of a boundary on inference: when enrollment is extremely limited and no analysis is reported, a descriptive result should remain descriptive. It can document observed counts, but it cannot carry the certainty of an adequately informative comparison. Making that distinction explicit helps prevent absence of recorded events from being mistaken for evidence of no risk or for proof that treatments perform alike.

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 central limitation is the small enrollment: the record lists 2 participants, with one in each arm. The registry states that enrollment did not reach the target number needed before termination and was insufficient to produce statistically reliable results. It does not report the target number, so the size of the shortfall cannot be assessed from the record.

The study status is terminated, but the reason for termination and date of termination are not reported in the registry record. The registry lists a start date and primary completion date, but does not explain the circumstances leading to termination. These details would help readers understand how the study ended and whether the planned follow-up was completed.

The record posts no statistical analyses, no inferential comparison, and no confidence interval or p-value for the primary endpoint. It does not report a pharmacokinetic result, although pharmacokinetics is part of the official title and stated study aim. No secondary outcomes are posted. Details of the statistical analysis plan, analysis populations, and missing-data handling are not reported in the registry record.

Further limitations include the lack of participant characteristics, dose amounts, event-level safety descriptions, and clarity about which roles were masked. The primary endpoint’s title includes severity, but the registry does not post a severity breakdown. The safety listings report no serious or other adverse events and no deaths in either group, but the numbers at risk are one per arm. Those observations cannot characterize uncommon events or support a stable comparison. These limitations mean the record offers only a narrow account of the enrolled participants and does not permit conclusions about treatment differences or broader safety experience.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Tolerability and the Pharmacokinetics of Ridinilazole in Adolescent Subjects — NCT04802837.
• Registry record last updated 2023-08-21; status last verified 2023-07.
• Results first posted 2023-08-21.
• 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 NCT04802837, a Phase 3 randomized, quadruple-masked, parallel-group, active-controlled study of ridinilazole compared with vancomycin in adolescent subjects with Clostridioides difficile infection. Ridinilazole and vancomycin were administered with matching placebo schedules for 40 doses over 10 days. The study’s stated aims included safety, tolerability, and ridinilazole pharmacokinetics.

Enrollment was 2, with one participant in each arm. The primary outcome was incidence and severity of treatment-emergent adverse events, assessed using CTCAE v4 until study completion (Day 100). The posted primary outcome value was zero participants in each arm. The safety record lists no serious adverse events, other adverse events, or deaths in either group.

The study status is terminated. The registry states that no analysis was done because enrollment did not reach the target number needed before termination and was insufficient to produce statistically reliable results. No secondary outcomes or analyses are posted. The record therefore supports a descriptive account of a very small enrolled sample, not a reliable comparative estimate or a conclusion about broader treatment effects.