Long Term Open-label Study Evaluating Safety of Diacerein 1% Ointment Topical Formulation in Subjects With Epidermolysis Bullosa Simplex: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long Term Open-label Study Evaluating Safety of Diacerein 1% Ointment Topical Formulation in Subjects With Epidermolysis Bullosa Simplex (NCT03389308), a na phase 2 study. The primary outcome is Treatment-emergent Adverse Events.

2. Clinical Question

3. Trial Design

This was a Phase 2, international, multicenter, open-label, long-term extension study of diacerein 1% ointment in participants with epidermolysis bullosa simplex. The registry lists the study as completed, with enrollment of 51. It began on 2017-12-01, and the primary completion date was 2020-04-17. These dates describe the study record; they do not by themselves establish how long any individual participant was followed.

The design was single-group, with no allocation to separate treatment arms and no masking. Participants with active lesions, as determined by investigator clinical assessment, began applying the ointment once daily at home to their EBS lesions for 8 weeks. The arm description also refers to an 8-week off-treatment period after the treatment period, during which participants used only the specified non-study approach. The description available in the registry record is incomplete, so further details of that period are not reported in the registry record.

The study objective was to evaluate long-term safety and tolerability over 2 treatment cycles in participants who had previously taken part in CCP-020-301 or CCP-020-101. This extension-study population is distinct from a group recruited without that prior-trial condition. The registry does not report how many participants completed each cycle, the amount of ointment used, or participant-level exposure duration.

Because the study was open-label and single-group, it was not designed as a randomized comparison. The posted event counts describe participants in the diacerein group; they cannot establish how those counts would compare with an untreated group or with another treatment under the same study conditions. A sample-size justification and a more detailed protocol-level statistical plan 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: All subjects who received at least one application of diacerein 1% ointment.

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 Treatment-emergent Adverse Events, measured over up to 52 weeks.

The primary endpoint was Treatment-emergent Adverse Events. It measures the number and percentage of participants with any treatment-emergent adverse event in the safety population: all subjects who received at least one application of diacerein 1% ointment. The timeframe was up to 52 weeks. The outcome unit is participants, so the endpoint concerns how many people experienced an event, rather than the total number of event episodes.

Safety endpoints of this kind are used to describe the occurrence of unwanted medical events during or after exposure to an intervention. Counting participants affected gives a participant-level view of whether an event was reported at least once. It does not, by itself, describe event severity, duration, recurrence, or whether the event was judged related to treatment. Those details require additional definitions or results, which are not reported in the registry record.

The posted record gives safety counts, including 21 participants with other adverse events and 0 participants with serious adverse events among 51 at risk. The registry does not report an analyzed percentage for the primary endpoint or a formal estimate of uncertainty for that outcome. The distinction between an event count and an analysis of a treatment effect is important: in a single-group study, the count describes what was recorded in the study population, not a difference attributable to treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary safety outcome: whether a participant experienced an event. The primary measure is the number and percentage of participants with any treatment-emergent adverse event, with participants rather than event episodes as the unit. The timeframe is up to 52 weeks, and the safety population includes anyone who received at least one application. The posted record lists 51 participants at risk. No formal analysis result for the primary endpoint is reported in the registry record.

What does a participant-level event count represent?

A participant-level count records whether each person experienced at least one qualifying event during the defined observation period. If a participant experiences multiple episodes, a count of participants affected still counts that person once. This differs from an event-frequency measure, which would count each episode, and from a rate, which would relate event occurrence to time at risk. The registry outcome is described in terms of participants, and event totals or person-time rates are not reported in the registry record.

The posted safety figures distinguish serious adverse events from other adverse events. The record lists 0 participants with serious adverse events and 21 participants with other adverse events, each among 51 at risk. The categories should be read as the recorded registry categories; further definitions, event-level descriptions, and participant-level overlap between categories are not reported in the registry record. The figures do not establish how many distinct event episodes occurred.

Why is a comparison important?

General statistical explanation: an intervention effect is commonly expressed by comparing outcomes between groups that differ in treatment but are otherwise made comparable by the design or analysis. A randomized control group can help distinguish differences associated with treatment from differences due to chance or other factors. This study is single-group and open-label, with no allocation to a comparator. It therefore provides a description of events among treated participants, not a between-group treatment-effect estimate.

For the same reason, a p-value for a treatment contrast is not available from the posted design and results. A p-value tests a specified hypothesis under a particular analysis; it is not a direct measure of the size, clinical importance, or certainty of an effect. No p-value, confidence interval, or comparative effect estimate for the primary endpoint is reported in the registry record. No analysis method beyond the endpoint’s count-and-percentage description is reported in the registry record.

How should uncertainty be understood?

General statistical explanation: observed counts are subject to sampling variability. A confidence interval can express the uncertainty around an estimated event frequency, while an interval for a comparison can express uncertainty about a difference or ratio. Such intervals depend on the chosen statistical model and the available data. No interval is reported for the event counts, and no new interval can be inferred from the posted summary without performing a separate calculation.

General statistical explanation: exposure duration also matters in safety analyses. If participants are followed for different lengths of time, a simple participant count may not capture differences in time available for events to be observed. Event rates can account for person-time when suitable exposure data are available. The registry describes a timeframe of up to 52 weeks but does not report participant-level follow-up or person-time, so the degree of variation in observation is not reported in the registry record.

What are the planning illustrations?

The sample-size calculations associated with this analysis are planning illustrations, not observed trial results and not the study’s original design justification. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations consider detecting a stated fraction of an observed effect. That hypothetical two-arm setup does not match this single-group study, which had no randomized comparator.

General statistical explanation: a planning calculation asks how many participants might be needed for a future study under specified assumptions about the effect, variability, significance level, power, and design. Such a calculation is conditional on those assumptions. It is not a measure of the probability that the completed study’s finding is true, and it does not create evidence of an effect. In particular, planned sample sizes should not be described as observed power. The registry does not report the trial’s own sample-size justification or a protocol-level statistical analysis plan.

Finally, the record lists no analyses. That means the registry does not report a statistical model, covariate adjustment, handling of repeated events, or sensitivity analysis for the primary outcome. These methods should not be inferred from the endpoint description or from the fact that safety counts are posted.

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("Diacerein 1% Ointment")
n      <- c(51)
events <- c(40)
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  Diacerein 1% Ointment  51  40  78.4  64.7  88.7  65.4  87.5  65.3  87.5

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint concerns participants with any treatment-emergent adverse event. The registry lists 1 outcome measure and 0 analyses. It does not report whether multiple outcomes or statistical tests were planned, whether any multiplicity adjustment was considered, or whether a formal testing hierarchy was used. Without reported inferential tests, the record does not support a claim about adjustment for multiple comparisons. These details are not reported in the registry record.

The registry defines the safety population as all subjects who received at least one application of diacerein 1% ointment. This is a stated analysis population definition, but it does not explain how participants with incomplete follow-up were handled. The record does not report the number of participants who discontinued, the reasons for discontinuation, missing event assessments, or methods used to address missing data. It is also not reported whether participants with different exposure durations were analyzed in any specific way.

General statistical explanation: missing outcome information can affect an event proportion if participants without complete assessment differ from those with complete assessment. Appropriate handling depends on when and why information is missing and on the analysis objective. No assumptions about missingness or imputation should be attributed to this study because those procedures are not reported in the registry record.

The endpoint timeframe is up to 52 weeks, but participant-level follow-up and exposure are not described. Accordingly, the posted counts should not be interpreted as if every participant necessarily had identical observation time. The registry also does not report a separate analysis population, protocol deviations, or sensitivity analyses. These omissions restrict evaluation of how robust the descriptive counts are to incomplete follow-up or alternative analytic choices.

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 registry’s serious adverse event figure is 0 participants affected among 51 at risk. The death count is also 0. These are recorded counts for the diacerein 1% ointment group; they do not mean that the study had a comparator showing a difference in serious-event risk. No serious adverse event terms are listed in the posted record.

The other adverse event figure is 21 participants affected among 51 at risk. It is a count of participants, not a count of all event episodes. The record does not provide event-level descriptions, severity classifications for these other events, causal assessments, or information about overlap with the serious-event category. Further details are not reported in the registry record.

General statistical explanation: zero observed events does not establish that the underlying event risk is zero. The uncertainty around a zero count depends on the amount of information and the observation period, among other features. No confidence interval is reported for the serious adverse event count. Because follow-up and exposure duration for individual participants are also not reported, the count alone does not describe person-time-based risk.

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

The results describe safety events recorded among participants who received diacerein 1% ointment in this open-label, single-group study. The registry reports 21 participants with other adverse events, 0 with serious adverse events, and 0 deaths among 51 at risk. Those figures are the available descriptive counts; the registry does not report a formal analysis of the primary endpoint or a comparative estimate.

The findings do not establish whether the ointment caused any particular event. The study lacks a concurrent control group, and the record does not report causal assessments for the posted events. Without a comparator, differences in event occurrence cannot be attributed to treatment by statistical comparison. The counts also do not describe severity, timing, recurrence, or the number of event episodes.

The absence of recorded serious adverse events in this study is a description of the observed registry count, not proof that serious events are impossible or that risk is absent. Likewise, the count of other adverse events does not by itself establish a treatment-related safety problem. Both statements would require evidence beyond an isolated group count.

The results apply most directly to the study population: participants with EBS who had previously participated in CCP-020-301 or CCP-020-101 and who received at least one application. The registry does not report enough detail about participant characteristics, individual exposure, or completeness of follow-up to determine how broadly the counts apply to other populations or settings.

The study’s stated goal was long-term safety and tolerability over 2 treatment cycles, while the endpoint timeframe was up to 52 weeks. Individual follow-up and treatment exposure are not reported in the registry record. Readers should therefore distinguish the planned or stated observation window from a known duration of observation for every participant. Overall, the record offers a limited descriptive account of reported safety counts, rather than a controlled assessment of comparative safety or a precise estimate of event frequency.

14. Why This Trial Matters Statistically

Safety studies often need to describe events that may be uncommon, varied in severity, or difficult to interpret without context. A registry record can make the endpoint definition, safety population, observation window, and observed counts accessible. In this study, those details identify a participant-level safety outcome in a specific group of participants with EBS and provide counts for serious and other adverse events.

The design is statistically important because it determines what conclusions the data can support. This was an open-label, single-group extension study, not a randomized comparison. Its event counts can characterize what was recorded among participants receiving the ointment, but cannot estimate a treatment difference against a concurrent control. Recognizing that distinction prevents descriptive safety information from being mistaken for a comparative effect.

The study population also matters. Participants had prior involvement in other studies, and the safety population included those who received at least one application. These features define the group represented by the counts. They also make clear that the results should not automatically be generalized to people outside that study context.

The record’s limits are instructive for statistical reading. The primary endpoint is described as a number and percentage, but the analyzed percentage, interval estimate, and inferential analysis are not reported. Individual follow-up, exposure time, missing-data methods, and event-level details are also not reported. Such information affects how precisely safety can be characterized and how results can be compared across studies.

For clinical researchers and biostatisticians, the central lesson is to align interpretation with design and reporting. Counts can be useful, but their meaning depends on the population, outcome definition, observation period, and completeness of follow-up. A planned sample-size illustration cannot substitute for an observed comparison, and a zero count should not be treated as proof of zero risk. The registry supports a cautious descriptive reading, with important questions remaining unanswered.

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 concurrent comparator. Because the registry describes a single-group, open-label study, the posted event counts do not provide a controlled estimate of the safety difference between diacerein 1% ointment and another treatment or no treatment. Confounding by the underlying condition and other factors cannot be separated from treatment exposure using these counts alone.

The study enrolled participants who had previously participated in CCP-020-301 or CCP-020-101. The registry does not report how this group compares with other people with EBS, so generalizability beyond this study population is uncertain. The available record also does not report detailed participant characteristics that could help readers assess representativeness.

Although the primary endpoint is defined as the number and percentage of participants with any treatment-emergent adverse event, the analyzed percentage and its uncertainty are not reported. The registry lists 0 serious adverse events and 21 participants with other adverse events among 51 at risk, but does not provide event-level descriptions, timing, severity for other events, or treatment-relatedness assessments. These gaps limit interpretation of the nature and clinical context of the events.

The endpoint timeframe is up to 52 weeks, but participant-level follow-up and exposure duration are not reported. The record does not describe completion, withdrawals, missing assessments, or missing-data handling. Thus, it is not possible to assess whether all participants were observed for similar periods or whether incomplete follow-up affected the counts.

Finally, no statistical analyses are listed. A detailed statistical analysis plan, sample-size justification, multiplicity approach, and sensitivity analyses are not reported in the registry record. The study’s safety results should therefore be read as limited descriptive information rather than as a complete inferential assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long Term Open-label Study Evaluating Safety of Diacerein 1% Ointment Topical Formulation in Subjects With Epidermolysis Bullosa Simplex — NCT03389308.
• Registry record last updated 2020-09-16; status last verified 2020-08.
• Results first posted 2020-09-16.
• 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

NCT03389308 is a completed Phase 2, international, multicenter, open-label, single-group extension study of diacerein 1% ointment in participants with epidermolysis bullosa simplex. Enrollment was 51. The study began on 2017-12-01, and primary completion was 2020-04-17.

The primary endpoint was the number and percentage of participants with any treatment-emergent adverse event in the safety population, over up to 52 weeks. The registry reports 21 participants with other adverse events, 0 with serious adverse events, and 0 deaths among 51 at risk. It lists 0 analyses. A comparator, formal inferential results, participant-level follow-up, and missing-data methods are not reported in the registry record.