P3 Long Term Safety Study of Once Daily SB204 in Acne: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for P3 Long Term Safety Study of Once Daily SB204 in Acne (NCT02798120), a na phase 3 study. The primary outcome is Number of Subjects With Adverse Events Ongoing From Parent Study at Start of Study NI-AC303).

2. Clinical Question

3. Trial Design

This was a Phase 3, multi-center, open-label, single-group study of SB204 4% once daily in acne vulgaris. The registry lists enrollment as 601 and the study status as completed. The record gives a start date of 2016-05-12 and a primary completion date of 2017-04.

All participants received the same study treatment, but their prior treatment differed. Those who had been assigned to SB204 in NI-AC301 or NI-AC302 continued SB204, while those who had been assigned to Vehicle Gel in those parent studies received SB204 4% in NI-AC303. The record describes the former group as SB204 Experienced and the latter as SB204 Naive. These labels track prior exposure; they do not create a concurrent control group.

The study was open label, so treatment was not masked. Allocation is listed as not applicable, and the registry cautions that the groups are not a like-for-like control comparison. This matters when interpreting differences between their safety counts: the groups had different treatment histories, and the study design does not establish a randomized contrast between them.

The primary outcome was assessed at baseline for NI-AC303. That baseline corresponds to the final Week 12 visit of the parent studies. The record describes participants who had received SB204 in a parent study as continuing treatment for 40 more weeks. It does not give the same continuation description for those who had received Vehicle Gel, beyond stating that they received SB204 4% once daily in NI-AC303.

The registry lists tolerability assessments and inflammatory and non-inflammatory lesion counts among the secondary outcomes. Numerical results for those outcomes 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

Analysis population for the primary outcome, as defined in the registry: Safety population There were 59 subjects in the SB204 Experienced group with 104 ongoing AEs at the time of rollover and 62 SB204 Naive subjects with 97 ongoing AEs at the time of rollover.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety population. As this was an open label, long term safety study, all subjects were in the safety population.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Adverse Events Ongoing From Parent Study at Start of Study NI-AC303), measured over Baseline.

The primary endpoint counts participants with at least one adverse event that was still ongoing when they entered NI-AC303. It is measured at baseline, defined as the final Week 12 visit of NI-AC301 and NI-AC302. The outcome therefore captures events carried over from the pivotal studies, rather than events first occurring during follow-up in NI-AC303.

The registry reports 59 participants in the SB204 Experienced group with 104 ongoing adverse events at rollover, and 62 participants in the SB204 Naive group with 97 ongoing adverse events at rollover. The participant counts and event counts are different quantities: the endpoint title concerns participants, while the description also reports the number of ongoing events. They should not be treated as interchangeable.

This measure is useful for describing the safety status of participants at the transition between studies and for distinguishing ongoing events from events arising later. It does not, by itself, estimate a treatment effect or establish whether SB204 caused an event. The registry record does not report a comparative analysis of this endpoint or a statistical test for the difference between the groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

A participant count records how many people meet a stated event definition. Here, the primary outcome asks whether a participant had at least one adverse event ongoing at rollover. The registry separately reports ongoing event counts, which need not match participant counts because an individual may have more than one event. The record gives both kinds of counts for the two prior-treatment groups, so it is important to keep the units distinct.

What does the baseline mean in this study?

The primary outcome’s timeframe is baseline, but this is not a baseline measured before the parent studies began. The record defines NI-AC303 baseline as the final Week 12 visit of NI-AC301 and NI-AC302. Consequently, the endpoint describes events still in progress at the transition into NI-AC303. It is not a count of events newly arising after participants began the current study treatment.

How should the group labels be read?

SB204 Experienced and SB204 Naive refer to previous assignments in the parent studies. In NI-AC303, both groups received SB204 4% once daily. The registry lists allocation as not applicable, identifies a single-group model, and warns that the groups are not a like-for-like control comparison. Their counts are descriptive group summaries, not results from a randomized comparison in this study.

General statistical context: A concurrent control group can help distinguish changes associated with treatment from changes over time or other influences. In a single-group study, changes in event counts cannot be separated from those other influences in the same way. Prior treatment history may also affect what is observed at entry. These general considerations explain why a simple contrast between the Experienced and Naive groups should not be treated as a causal estimate.

What would an uncertainty interval add?

General statistical context: A confidence interval expresses the uncertainty around an estimated quantity under a specified statistical model. It can show which effect sizes remain compatible with the data, rather than presenting only a point estimate. The registry record does not report confidence intervals or a comparative statistical analysis for the primary outcome. No interval or precision estimate can be inferred from the reported counts alone without additional assumptions and calculations.

How should the serious-event counts be interpreted?

The record lists participants at risk and participants affected for serious and other adverse events. Those counts are summaries of the safety population and do not, by themselves, quantify exposure time or account for differing follow-up. The record does not report a time-to-event analysis for these figures. It also lists selected serious-event terms, but the listed information does not establish causality or supply a comparative test.

General statistical context: Rates can account for differences in exposure time when suitable person-time data are available, while simple counts do not. This is a general distinction, not a claim that an exposure-adjusted analysis was performed. The necessary person-time summaries and analysis details are not reported in the registry record.

What do the planning assumptions mean?

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the target effect is a stated fraction of the observed effect. Such calculations describe hypothetical future planning under assumptions; they are not observed power and do not show the probability that this study detected an effect. The record does not report a protocol-based sample-size justification or enough detail to interpret a specific planning result.

General statistical context: Statistical power and sample-size planning depend on the effect to be detected, variability, design, and analysis assumptions. If the true effect is smaller than the effect used in planning, a study may be less likely to distinguish it from random variation. Planning illustrations are conditional on their assumptions and should not be read as evidence that an observed result is reliable or clinically important.

The registry record does not report the statistical tests, model specifications, confidence intervals, or analysis details for the primary endpoint. It lists no analysis entries. This means the record does not document those procedures; it does not establish what analyses may have been conducted outside the registry record.

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("SB204 Experienced", "SB204 Naive")
n      <- c(296, 305)
events <- c(59, 62)
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  SB204 Experienced  296  59  19.9  15.5  24.9  15.8  24.9  15.8  24.9
ARM  SB204 Naive  305  62  20.3  16.0  25.3  16.2  25.2  16.2  25.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes, including the primary count of ongoing adverse events at rollover and secondary outcomes concerning tolerability and inflammatory and non-inflammatory lesion counts. When several outcomes are assessed, the chance of at least one apparently notable result can be affected by how many comparisons are made and by the analysis plan. General statistical context: Methods for handling multiple comparisons can help control that issue, but the registry record does not report a multiplicity adjustment or a prespecified hierarchy among the outcomes.

The record lists 0 analysis entries. It does not report the statistical analysis plan, the tests used, or whether analyses were adjusted for covariates. The absence of analysis entries in the registry record should not be taken to mean that no analyses were performed; it means those details are not reported in the registry record.

Missing-data procedures are not reported in the registry record. There is no reported description of how missing visits, incomplete outcome assessments, or withdrawals were handled. The record identifies the safety population for the primary outcome but does not provide a broader account of analysis populations or say how membership in those populations was determined.

These omissions limit assessment of how the reported summaries relate to all enrolled participants and how robust any outcome analysis may be to incomplete observations. No imputation method, sensitivity analysis, or missingness assumption is reported in the registry record.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (0.3%), anxiety (0.3%), conduct disorder (0.3%), gastrointestinal haemorrhage (0.3%), sepsis (0.3%).

For serious adverse events, the registry lists 4 affected participants among 296 at risk in the SB204 Experienced group and 2 among 305 at risk in the SB204 Naive group. For other adverse events, it lists 34 among 296 and 32 among 305, respectively. The record lists 0 deaths in each group. These are descriptive counts, not evidence of a statistically established difference between groups.

The groups reflect prior treatment history, and all participants received SB204 4% once daily in NI-AC303. As the registry cautions, they are not a like-for-like control comparison. The counts cannot establish whether treatment caused an event, and the record does not report an inferential analysis or uncertainty intervals for these figures.

The record lists Appendicitis, Anxiety, Conduct Disorder, Gastrointestinal Haemorrhage, Sepsis, and Back Pain as serious adverse-event terms, each at 0.3%. These listings identify terms and their reported percentages; they do not establish causation. The registry record does not report further details about the events’ timing or relationship to treatment.

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

The record documents an open-label study in which all participants received SB204 4% once daily, with different prior treatment histories represented by the Experienced and Naive groups. Its primary endpoint describes ongoing adverse events carried over from the parent studies at rollover. The reported participant and event counts provide a snapshot of that transition, not an estimate of new-event risk attributable to NI-AC303 treatment.

The registry also gives descriptive serious and other adverse-event counts and lists selected serious-event terms. Those figures can inform a summary of what was recorded, but the study design and reporting do not support a controlled treatment-effect conclusion. The two groups are not a randomized, like-for-like comparison in this study, and both received SB204 during NI-AC303.

The findings do not establish that SB204 caused any listed event, nor do they establish that it prevented or reduced events. No comparative statistical test or confidence interval for the primary outcome or safety counts is reported in the registry record. Numerical results for the listed tolerability and lesion-count outcomes are also not reported in the registry record.

General interpretation: A descriptive count is most informative when its event definition, population, timeframe, and comparison are clear. Here, the primary outcome’s timeframe is the rollover baseline, and the group labels encode prior treatment. Keeping those features in view prevents the baseline counts from being mistaken for treatment-emergent results or for a controlled estimate of benefit or harm.

The record can therefore be read as a description of a long-term, open-label safety study and its posted event summaries. It does not, on the registry entries reported, resolve comparative effectiveness or establish causal safety conclusions.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a carryover safety endpoint and events arising during follow-up. The primary measure counts ongoing adverse events at rollover from the parent studies. A reader who overlooks the endpoint’s baseline timeframe could mistake those events for new events observed after entry into NI-AC303. The record’s definition of baseline is therefore central to interpreting the endpoint.

The study also illustrates why treatment history matters when reading group summaries. SB204 Experienced and SB204 Naive describe participants’ prior assignments, while every participant in the current study received SB204 4% once daily. The registry explicitly warns that these groups are not a like-for-like control comparison. Treating their counts as if they came from randomized concurrent arms would overstate what the design can establish.

Finally, the record separates participant counts from event counts and reports serious and other adverse-event summaries without a reported comparative analysis. These distinctions are fundamental to sound interpretation: the unit being counted, the period being described, and the design supporting comparison all affect the meaning of a number. The registry’s omissions about analysis methods, missing data, and uncertainty further limit conclusions from the posted summaries.

The study thus provides a useful example of how registry safety results require careful attention to endpoint timing, prior exposure, and the limits of descriptive evidence. The figures are informative as recorded summaries, but they should not be stretched into causal or comparative claims unsupported by the design and reported analysis.

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.

This is an open-label, single-group study, and there is no concurrent control group receiving a different treatment. The registry states that allocation is not applicable and that the prior-treatment groups are not a like-for-like control comparison. Because every participant received SB204 4% in NI-AC303, the study cannot use those groups as a randomized treatment contrast.

The primary outcome is measured at rollover and concerns events ongoing from the parent studies. It therefore does not by itself describe new adverse events during NI-AC303. The Experienced and Naive groups also differ by prior treatment assignment, so their baseline summaries may reflect different histories. The registry record does not provide information to disentangle those histories from other influences.

The record does not report statistical tests, confidence intervals, covariate adjustment, or a detailed analysis plan. It does not report procedures for missing data or a fuller description of analysis populations beyond identifying the safety population for the primary outcome. Numerical results for the listed secondary outcomes are not reported in the registry record.

The serious and other adverse-event figures are presented as counts, without a reported comparative analysis or time-to-event results. The registry lists selected serious-event terms but does not establish their relationship to treatment. These reporting and design limitations mean that the posted summaries are best interpreted descriptively, rather than as evidence of a causal treatment effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: P3 Long Term Safety Study of Once Daily SB204 in Acne — NCT02798120.
• Registry record last updated 2023-05-12; status last verified 2023-05.
• Results first posted 2023-05-12.
• 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

NCT02798120 is a completed Phase 3, multi-center, open-label, single-group study of once-daily SB204 4% in acne vulgaris. The registry lists enrollment of 601, a start date of 2016-05-12, and primary completion in 2017-04. Participants who had received SB204 in the parent studies were classified as SB204 Experienced; those who had received Vehicle Gel were classified as SB204 Naive. Both groups received SB204 4% in NI-AC303.

The primary outcome counts participants with at least one adverse event ongoing from a parent study at rollover. Its baseline is defined as the final Week 12 visit of the parent studies. The record reports ongoing-event participant and event counts for each prior-treatment group, plus descriptive serious and other adverse-event counts. It does not report comparative statistical analyses, uncertainty intervals, missing-data methods, or numerical results for the listed secondary outcomes.