A Phase I Study of HY209 Gel in Healthy Male Volunteers for Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase I Study of HY209 Gel in Healthy Male Volunteers for Atopic Dermatitis (NCT03492398), a randomized phase 1 study. The primary outcome is Incidence of Treatment Emergent Adverse Events.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, placebo-controlled, quadruple-masked, parallel-group Phase I trial sponsored by Shaperon. Its title identifies the study as an investigation of HY209 gel in healthy male volunteers for atopic dermatitis. The stated purpose was to investigate safety, tolerability and pharmacokinetics following transdermal administration. The record lists enrollment of 56 and marks the study as completed. Its recorded start date is 2018-01-29, and its primary completion date is 2019-03-21.

The arms are organized into two dosing cohorts. Cohort A received a single dose of placebo or HY209 gel at 0.05%, 0.1%, 0.3% or 0.5%. Cohort B received multiple doses of placebo or HY209 gel at 0.1%, 0.3% or 0.5%. The posted primary outcome group sizes are 8 for Cohort A placebo and 6 for each of its HY209 groups; the Cohort B groups each list 6 participants. These are the group sizes attached to the outcome results, not a breakdown of the full enrollment.

The cohort structure matters when reading the counts: single-dose groups should be interpreted in relation to their Cohort A placebo group, and multiple-dose groups in relation to Cohort B placebo. The registry record does not state a formal pooled comparison across doses or cohorts. It also does not report a statistical analysis plan or an explanation of the allocation process beyond identifying the study as randomized. Details such as sequence generation, concealment, masking procedures and the planned analysis populations 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.

Only the first 6 of 9 groups are shown.

Overall Study

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.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Treatment Emergent Adverse Events, measured over upto Day 8(single dosing), upto Day 38(multiple dosing).

The primary endpoint is the number of participants with treatment-emergent adverse events. The record defines the count to include participants with abnormal laboratory values and/or adverse events related to treatment. It is a binary participant-level outcome: for each group, the result is a count of participants who met the endpoint, rather than a measure of the number of separate events or their severity. The timeframes were upto Day 8 for single dosing and upto Day 38 for multiple dosing.

Counting participants with an event is commonly used in early-phase research to describe how often a safety outcome was observed in the groups under study. As a general statistical point, participant counts can give a straightforward account of observed events, but they do not by themselves describe event timing, duration, severity, or whether a participant had more than one event. The record's endpoint combines abnormal laboratory values and adverse events related to treatment, so the posted count should be read using that stated definition.

The study summary also names pharmacokinetics as an objective, but no pharmacokinetic outcome is posted among the outcome measures in this record. The primary endpoint is not an efficacy measure of atopic dermatitis symptoms or disease control. No secondary outcomes are posted in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is binary at the participant level: a participant either met the stated endpoint during the relevant observation window or did not. The registry reports counts for each arm, along with the group size used for that outcome. This form of summary makes the observed number of affected participants visible, but a count alone is not a comparative effect estimate. It does not indicate how likely the observed difference between groups would be under a specified statistical model.

What does a confidence interval communicate?

In general, a confidence interval is a range of values generated by a statistical procedure to express uncertainty around an estimate. For a binary outcome, an interval might accompany a group-level event proportion or a contrast between groups. Wider intervals generally indicate less precision, while narrower intervals indicate more precision, subject to the method and assumptions used. No confidence intervals are reported for the primary endpoint in the registry record, and none can be inferred from the counts alone without choosing and applying an analysis method.

Why are separate cohort comparisons important?

The record separates single dosing in Cohort A from multiple dosing in Cohort B. The corresponding placebo groups are also separate. As a general design principle, a treatment comparison should reflect the groups that share the relevant dosing schedule and observation conditions. Combining dose groups or cohorts can change the question being answered and may obscure differences in exposure or follow-up. The registry record does not report a pooled analysis, a dose-trend model, or an adjusted comparison between cohorts.

The listed observation windows are upto Day 8 for single dosing and upto Day 38 for multiple dosing. Those timeframes define the period over which the primary outcome was assessed as described in the record. A longer observation window can allow more time for an event to be detected; this general consideration is one reason that counts from differing follow-up periods should not automatically be compared as if they shared the same measurement conditions. The record does not describe event timing or provide a time-to-event analysis.

What is the role of randomization and masking?

Randomization is generally intended to reduce systematic differences between groups at assignment, while masking is intended to limit the influence of knowledge of treatment assignment on care or assessment. The registry identifies the study as randomized and quadruple masked. It does not describe sequence generation, allocation concealment, which roles were masked, or whether masking was assessed. These implementation details are not reported in the registry record, so the labels alone do not establish how those procedures were carried out.

The record identifies the study as parallel-group. In general, a parallel design assigns participants to a group and evaluates outcomes in that group, rather than having each participant receive multiple assigned treatments in sequence. The posted results align with distinct arm labels, but the registry does not provide further details about treatment allocation or participant flow.

What can be inferred from the available analysis?

The registry lists no posted analyses for this outcome, and it gives no confidence intervals or p-values for a comparison. It also does not report whether a particular analysis population was defined, how missing outcome observations were handled, or whether any adjustment was planned. Without those details, the arm counts are best treated as descriptive. A statistical test or model would require choices about the estimand, comparison, and assumptions that are not documented in the registry record.

As a general point, binary outcomes can be analyzed using methods designed for event counts or event proportions, but the method should match the design, the estimand and the amount of information available. With small groups, estimates may be unstable, and standard approximations may not perform well. This is a general methodological caution; the record does not report a selected inferential method or a precision estimate for the posted primary results.

How should planning calculations be understood?

Any sample-size values accompanying this record are planning illustrations based on an observed effect, with a stated two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration is not the trial's documented design justification and is not observed power. A planning calculation asks what size a hypothetical future comparison might require under chosen assumptions. It does not revise the observed results or demonstrate that this trial had a particular probability of detecting an effect. The registry record does not report its own sample-size justification or design assumptions.

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("Cohort A Placebo", "Cohort A HY209 0.05% Gel", "Cohort A HY209 0.1% Gel", "Cohort A HY209 0.3% Gel", "Cohort A HY209 0.5% Gel", "Cohort B Placebo")
n      <- c(8, 6, 6, 6, 6, 6)
events <- c(4, 2, 2, 1, 0, 2)
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  Cohort A Placebo  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8
ARM  Cohort A HY209 0.05% Gel  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  Cohort A HY209 0.1% Gel  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0
ARM  Cohort A HY209 0.3% Gel  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Cohort A HY209 0.5% Gel  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Cohort B Placebo  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0

11. Multiplicity, Missing Data and Analysis Populations

The study includes several HY209 dose groups, a single-dose cohort and a multiple-dose cohort. Evaluating many dose-versus-placebo contrasts can raise a multiplicity issue: in general, the more statistical tests conducted, the greater the chance of at least one apparently notable result arising by chance if no adjustment or testing strategy is used. The registry record does not report a multiplicity adjustment, a prespecified testing sequence, or a statistical analysis plan. No comparative p-values are posted, so the record does not establish how multiple comparisons would have been handled.

The registry lists no secondary outcomes and no posted analyses. The primary endpoint group counts are available, but the analysis population is not specified. The record does not state whether the outcome was analyzed in all randomized participants, only participants who received treatment, or another defined population. It also does not report withdrawals, exclusions from the outcome analysis, or how missing observations were treated. These details are not reported in the registry record.

Missing-data methods matter because excluding participants with unavailable outcome information, or making assumptions about their outcomes, can affect an estimate. As a general statistical principle, the approach should be stated and justified, and sensitivity analyses may be useful when conclusions depend on assumptions about missing outcomes. No such approach or sensitivity analysis is described in this record. The posted arm counts should therefore be read as the reported results, without assuming a particular missing-data procedure or analysis population.

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 0.5% reporting threshold.

Most frequent non-serious adverse event terms

The separate adverse-event listing reports zero serious adverse events in every listed group and zero deaths in every listed group. For other adverse events, the counts were 2 of 8 in Cohort A placebo; 2 of 6 in Cohort A HY209 0.05%; 1 of 6 in Cohort A HY209 0.1%; 1 of 6 in Cohort A HY209 0.3%; and 0 of 6 in Cohort A HY209 0.5%. In Cohort B, the counts were 1 of 6 for placebo, 0 of 6 for HY209 0.1%, 1 of 6 for HY209 0.3%, and 1 of 6 for HY209 0.5%.

These figures describe the adverse-event categories reported in the safety listing; they are not the same endpoint as the primary count, which includes abnormal laboratory values and/or adverse events related to treatment. A report of zero serious events means none were recorded in those listed groups during the reported study context. It does not establish that a rare event could not occur, and the record does not provide a comparative statistical estimate for serious events.

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

The results establish what the registry record reports: participant counts meeting the primary endpoint in each single-dose and multiple-dose arm, alongside a separate listing of serious and other adverse events. They provide a descriptive account of observed events under the study's stated conditions and timeframes. The results do not supply comparative uncertainty estimates, and no sponsor analysis comparing two arms is posted.

Accordingly, differences in the observed counts should not be read as proof that one group had a higher or lower underlying risk than another. Counts from small groups are sensitive to individual outcomes, and the registry does not provide confidence intervals, p-values or an analysis plan that would support a formal comparative interpretation. The dose groups also belong to separate dosing cohorts with different follow-up windows.

The trial's stated purpose included safety, tolerability and pharmacokinetics. The primary endpoint concerns treatment-emergent adverse events, not clinical improvement in atopic dermatitis. The registry record does not post a pharmacokinetic outcome or a secondary efficacy outcome. These data therefore do not establish an effect on atopic dermatitis or resolve questions about longer-term treatment outcomes.

The record identifies healthy male volunteers as the study population. Its findings should be interpreted in that population and in the specific early-phase study context described. The record does not report results for people with atopic dermatitis. As a general limitation, observations from a small early-phase study may not characterize uncommon events or outcomes beyond its observation periods. The record's zero serious-event counts are descriptive findings, not evidence that serious events are impossible.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between descriptive counts and comparative evidence. The registry presents event counts by dose group and cohort, which makes the observed outcomes visible. Yet without a reported comparative analysis, confidence intervals or p-values, readers cannot assess the precision of a difference or whether a formal statistical test supports one.

The dose-escalation structure also illustrates why the comparison must be defined before interpreting patterns. Single-dose and multiple-dose regimens have separate placebo groups and different outcome windows. Reading every arm as part of a single ordered dose-response sequence would ignore that design distinction. A formal analysis would need to state which groups are compared and how the cohorts are handled; the registry does not report those details.

Another statistical lesson is that endpoint definitions and safety listings may not be interchangeable. The primary endpoint includes abnormal laboratory values and/or treatment-related adverse events, while the adverse-event listing separates serious events, other events and deaths. Counts across these summaries should be understood in the context of their stated categories rather than combined or substituted for one another.

Finally, the record shows why sample-size planning should be separated from observed evidence. Planning illustrations depend on chosen assumptions and do not supply missing precision estimates for this trial. The registry does not report its own sample-size justification, so those illustrations cannot establish the design rationale or the study's ability to detect a particular effect.

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 is reported as counts, without confidence intervals, p-values or an estimable two-arm comparison. The registry record gives no statistical analysis plan, so the intended comparisons, analysis methods and any multiplicity strategy are not reported. The analysis population and treatment of missing outcome data are also not reported in the registry record.

The study has multiple dose groups arranged across a single-dose cohort and a multiple-dose cohort. The cohorts have different observation windows, and the record does not report an analysis that accounts for those differences or formally evaluates a dose-response relationship. The posted arm sizes are small, which limits the amount of information in each group and makes counts sensitive to individual outcomes. This is a general interpretation of the group sizes, not a recalculated estimate of precision.

The primary endpoint's description combines abnormal laboratory values and/or adverse events related to treatment. The separate safety listing reports other adverse events, serious adverse events and deaths, but the record does not explain how the categories map to the primary endpoint. The reported primary counts and adverse-event listing therefore cannot be assumed to represent the same outcome definition.

The study was conducted in healthy male volunteers, and the registry record does not post results in people with atopic dermatitis. Although the study summary names pharmacokinetics as an objective, no pharmacokinetic result is posted among the outcome measures. No secondary outcomes are posted. The record does not report details about participant flow, withdrawals, missingness, protocol deviations, or the procedures used to implement randomization and masking.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase I Study of HY209 Gel in Healthy Male Volunteers for Atopic Dermatitis — NCT03492398.
• Registry record last updated 2021-01-29; status last verified 2020-03.
• Results first posted 2020-10-19.
• 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, placebo-controlled, quadruple-masked, parallel-group Phase I study of HY209 gel in healthy male volunteers. It lists enrollment of 56, with single-dose Cohort A groups and multiple-dose Cohort B groups. The primary outcome is the count of participants with treatment-emergent adverse events, including abnormal laboratory values and/or treatment-related adverse events, assessed upto Day 8 for single dosing and upto Day 38 for multiple dosing.

Arm-level counts are posted, as are separate serious and other adverse-event counts. No comparative analysis, confidence interval, p-value or secondary outcome is posted. The registry record does not report the analysis plan, analysis population, missing-data handling, multiplicity approach, or the study's sample-size justification.