Study to Determine Skin Irritation and/or Sensitization Potential of an Antifungal Cream Containing Trolamine (Repeated Insult Patch Test): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Determine Skin Irritation and/or Sensitization Potential of an Antifungal Cream Containing Trolamine (Repeated Insult Patch Test) (NCT04531540), a na phase 3 study. The primary outcome is Irritation Response Evaluation According to Erythema Scoring Scale During Induction Phase - All Enrolled Subjects.

2. Clinical Question

3. Trial Design

This completed study is registered as phase 3 and uses a single-group design. The registry records allocation as NA and masking as none. It lists 225 participants enrolled and describes female or male participants aged 18 - 79 years. The record gives a start date of 2013-09-09 and a primary completion date of 2013-10-18.

The intervention was Butenafine HCl 1% (BAY1896425). In the induction phase, participants received 0.2 g at an upper-back skin test site under an occlusive patch three times a week for a total of 9 applications. Test sites were evaluated for gross changes before each patch application and after the last patch removal. The registry description says these observations used an erythema scoring scale.

The brief study description outlines repeated applications to the same back area during the first 3 weeks, followed by a rest period of two weeks and a modified challenge involving the original and a nearby new skin area. It describes later skin checks after 2 and 4 days. The primary outcome, however, is identified as an induction-phase evaluation with a timeframe of after 4 weeks. The registry record does not provide a fuller account of how the challenge observations were incorporated into outcome analyses.

Because there is no comparison group, the design is suited to recording skin responses in participants exposed to the test cream, not to estimating a treatment contrast against a control. The registry record does not report a randomization procedure, a masking procedure, a separate control intervention, or a statistical analysis plan. It reports 4 outcome measures and 0 analyses. Those entries do not supply numerical results for the primary endpoint.

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: A total of 225 subjects were enrolled in the study and 222 received study treatment.

Overall Study

Reasons for not completing this period:

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 Irritation Response Evaluation According to Erythema Scoring Scale During Induction Phase - All Enrolled Subjects, measured over After 4 weeks.

The primary endpoint is titled “Irritation Response Evaluation According to Erythema Scoring Scale During Induction Phase - All Enrolled Subjects.” Its unit is test site, its parameter is number, and its timeframe is after 4 weeks. The registry description says sites were assessed for gross changes before each patch application and after the last patch removal. It identifies the Erythema Scoring Scale as the method for grading visible redness.

The scale distinguishes no visible erythema, slight and barely perceptible erythema, mild erythema, moderate erythema, marked erythema, and severe erythema, with scores from 0 through 4, including a score of 0.5. These ordered categories provide a structured way to describe the visible intensity of redness rather than relying only on an unstructured narrative. Recording observations at test sites is relevant to a repeated patch test because irritation is assessed locally where the cream and patch were applied.

The registry record does not report the number of sites in each category, a summary of scores, or any other numerical primary-endpoint result. It also does not specify how repeated site observations were combined into a participant-level summary. As a result, the endpoint definition explains what was assessed, but the posted results do not show the observed irritation pattern or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies an outcome scale and a single-group structure, but does not report a statistical analysis plan or numerical primary-outcome analysis. The concepts below explain how such information is generally interpreted; they do not describe analyses as having been performed in this study.

What does an erythema score represent?

An ordinal scale places observations into ordered categories. Here, the categories run from no visible erythema to severe erythema, with intermediate grades and a score of 0.5 for slight, barely perceptible erythema. The ordering conveys increasing visible redness, but the distances between categories are not automatically equal. For example, a move between adjacent grades cannot be assumed to represent the same change in redness at every point on the scale.

For an ordinal endpoint, a clear analysis usually states whether it reports category counts, a distribution across grades, a summary score, or a threshold-based outcome. Each answers a different question. Counts by grade describe how observations are distributed; a summary can condense the pattern but may hide category-level detail. A threshold outcome requires a stated definition of which grades count as a response. The registry describes the scoring categories but does not report which summary approach was used or provide the resulting data.

Why is the unit important?

The primary outcome lists test site as its unit. That matters because the assessment is made at a local application site, while people may contribute observations over repeated applications. If a participant has repeated measurements, those observations are related: measurements from the same person or site are generally not independent in the way observations from unrelated participants might be. An analysis that treats every repeated assessment as independent can understate uncertainty. Appropriate methods account for the clustering or repeated-measures structure when that structure is present and relevant.

The record says sites were evaluated before each patch application and after the last patch removal. It does not state how many observations per participant entered the primary summary, how missing visits were handled, or whether the analysis used each assessment or a selected assessment. It therefore is not possible to identify the statistical unit used for an analysis beyond the unit named in the outcome definition.

What does a single-group design allow?

A single-group study can describe the observations among participants who received the intervention. It does not directly estimate a difference between intervention and control groups. A comparison with a concurrent control group helps distinguish treatment-associated outcomes from changes that might also occur without the intervention or under another condition. Without that comparison, the interpretation is descriptive and cannot isolate the intervention effect through randomization.

Random assignment, when used, aims to balance known and unknown participant characteristics across groups on average. The registry lists allocation as NA and describes one group, so a randomized comparison is not reported. Masking can reduce some forms of influence on assessment or reporting, but masking is recorded as none. The record does not describe additional safeguards or independent assessment procedures.

How should uncertainty be understood?

A point estimate, such as a proportion or average, summarizes the observed sample. A confidence interval expresses uncertainty around an estimate under the assumptions of the statistical method. A wider interval generally indicates less precision, while a narrower interval indicates greater precision, though the interval does not remove potential bias or design limitations. For ordinal data, the chosen estimate and interval method should fit the scale and the sampling structure.

No numerical primary-outcome estimate or confidence interval is reported in the registry record. Consequently, neither the magnitude of an observed response nor its precision can be evaluated. Enrollment alone cannot substitute for an estimate and interval: the number of participants does not disclose their observed score distribution or the amount of variation in those observations.

Why can over-dispersion matter?

For count outcomes, a statistical model may assume a particular relationship between the mean and the variability. Over-dispersion occurs when the observed variation is greater than that assumed by a model. If ignored, uncertainty estimates can be too small, making findings appear more precise than they are. Methods that allow extra variation can be more appropriate when counts are more dispersed than the basic model expects. This is a general consideration, not a claim that the endpoint in this study was analyzed with a count model. The registry provides no model specification or dispersion assessment.

The primary outcome is recorded with a number parameter and test-site unit, but that description alone does not reveal the distribution of the data or the analysis method. A count of sites in categories, an ordinal score, and repeated observations can require different statistical treatment. The registry record does not report enough analytical detail to determine how these features were handled.

What can be inferred from the reported counts?

The adverse-event results provide counts of affected participants within the listed categories. These are descriptive safety summaries, not a comparative effect estimate. With no control group, the counts do not indicate how the event experience would have differed under another intervention or no intervention. They also do not supply information about the primary erythema score distribution.

In general, an analysis plan may define the population included, outcome handling, missing-data methods, and statistical procedures before outcomes are examined. Prespecification can help limit selective analysis choices. The registry record does not report a statistical plan, interim analyses, a sample-size justification, or methods for missing observations. No inference about those procedures should be drawn from the enrollment count or from the existence of a completed study registration.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures and 0 analyses. It does not report an analysis plan specifying which outcomes were primary or secondary in the statistical testing sequence beyond the primary endpoint title, nor does it describe any multiplicity adjustment. When several outcomes or comparisons are tested, multiplicity can increase the chance of at least one apparently notable result arising by chance. General approaches include defining a hierarchy of outcomes or adjusting the testing procedure, but the record does not say that any such approach was used.

The primary outcome population is identified as all enrolled subjects. The registry does not describe an analysis population for the other outcomes, nor does it state whether participants with incomplete assessments were included, excluded, or handled by a particular rule. Missing-data methods matter because results can be biased if the availability of observations is related to participants’ skin responses or other characteristics. No information about missing assessments, withdrawals, or the reasons for missingness is reported in the registry record.

The record also does not report a sample-size justification, interim analyses, or a statistical plan. These items are not safely inferred from enrollment or from the phase designation. Without details on outcome-level analysis populations, missing-data handling, and multiplicity, the statistical analysis cannot be reconstructed. These limitations are especially relevant because numerical results for the primary irritation endpoint are not reported.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

For the Repeated Insult Patch Test group, the registry lists 225 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 225 participants at risk and 6 affected. These are participant-level figures in the posted safety summary; they should not be confused with a count of every event episode or with the primary erythema endpoint.

The record does not list serious adverse-event terms. Deaths are not reported in the registry record. The other adverse events are not broken down by term in the information available, so their nature, timing, severity, and relationship to the study intervention cannot be described from these counts alone. The registry summary also does not establish whether any event was caused by the cream or by the patch procedure.

Because the study has no concurrent comparison group, these figures are descriptive rather than comparative. They do not estimate how the same participants’ event experience would have differed under a control condition. The absence of reported serious adverse events in this summary should be read as a statement about the posted count, not as proof that no safety concerns of any kind occurred.

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

The record establishes that a completed, single-group study evaluated repeated application of Butenafine HCl 1% using a patch-test procedure. It describes an induction schedule and identifies erythema scoring as the primary way to assess irritation at test sites. It also reports adverse-event summaries for the enrolled group. These details clarify what the study set out to observe and what safety categories are available in the registry.

The registry does not report numerical results for the primary erythema endpoint. It is therefore not possible to determine how many test sites had each grade, how severe the observed reactions were overall, or how precisely any response was estimated. The registry record also does not report an analysis method or uncertainty interval for that endpoint. The outcome definition should not be interpreted as a result.

The design does not include a control group, so it cannot provide a randomized comparison with another product or with no treatment. Any observed reactions in a single group would be descriptive; without comparative data, the study cannot isolate the effect of the cream from other explanations. The registry also does not provide a detailed accounting of the modified challenge observations or explain how those assessments were analyzed.

The adverse-event summary lists 0 participants affected by serious adverse events and 6 affected by other adverse events among 225 at risk. These figures do not describe the primary irritation scale, do not establish causation, and do not provide event-level detail for the other category. They should be interpreted as the safety information recorded, rather than as a complete account of every possible reaction.

In short, the posted record describes the study procedures and identifies what was assessed, but it leaves the central quantitative irritation result unavailable. It supports neither a claim that irritation was absent nor a claim about the frequency or intensity of irritation. Such conclusions would require outcome results and appropriate detail about their analysis.

13. Why This Trial Matters Statistically

This trial illustrates why an outcome definition and an outcome result are not interchangeable. The registry names a clinically interpretable feature—visible erythema—and gives an ordered scoring scale. Yet without the observed score distribution, the reader cannot tell what was seen at the test sites. A precise endpoint description is useful, but it cannot replace numerical findings.

The design also highlights the distinction between describing a response and estimating a comparative effect. A single-group repeated patch test can document observations under a specified exposure schedule. A concurrent comparison would address a different statistical question by helping estimate how outcomes differ across conditions. The registry identifies no such comparison, so the design and conclusions must remain descriptive.

Repeated assessments introduce another important statistical issue: observations from the same participant or test site may be related. The correct handling of that dependence affects uncertainty estimates. The record describes assessments around repeated applications but does not report how repeated observations were summarized or modeled. Without those details, readers cannot assess the analytical treatment of the measurement structure.

Finally, safety counts and the primary irritation endpoint answer distinct questions. The posted adverse-event summary gives affected-participant figures, while the primary outcome is a site-based erythema evaluation. Neither can stand in for the other. Separating these outcome types, and being explicit about what is and is not reported, helps prevent descriptive counts from being read as comparative evidence or as a complete account of skin responses.

14. 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 principal limitation for interpreting the study is that numerical results for the primary erythema endpoint are not reported in the registry record. Although the scale and assessment timeframe are described, there are no category counts or summary estimates. This prevents readers from evaluating the frequency, distribution, or precision of irritation responses.

The single-group design has no concurrent control. The observations therefore cannot establish a difference relative to another product or an untreated condition, and the study cannot use randomization to separate intervention effects from other influences. Masking is recorded as none, and the registry does not describe additional procedures for reducing assessment bias.

The registry does not explain how repeated site assessments were handled analytically, how missing observations were treated, or whether multiple outcomes were accounted for in a prespecified testing strategy. It also does not report a statistical analysis plan, interim analyses, or a sample-size justification. These omissions limit reproducibility and make it difficult to assess the assumptions underlying any analysis.

The brief description includes a modified challenge after a rest period, but the primary outcome is framed around the induction phase. The registry does not report numerical challenge results or explain their analysis. The adverse-event information is also limited: the record lists affected-participant counts but does not provide terms for the other adverse events or establish attribution. These limitations mean the posted record offers only a partial statistical account of the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Determine Skin Irritation and/or Sensitization Potential of an Antifungal Cream Containing Trolamine (Repeated Insult Patch Test) — NCT04531540.
• Registry record last updated 2020-11-17; status last verified 2020-10.
• Results first posted 2020-09-25.
• 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.

18. Record Summary

The registry record describes a completed phase 3, single-group repeated insult patch test of Butenafine HCl 1% (BAY1896425), with 225 participants enrolled. Allocation is listed as NA and masking as none. During induction, participants received 0.2 g under an occlusive patch at an upper-back test site three times a week for a total of 9 applications.

The primary endpoint concerns test-site irritation assessed with an erythema scoring scale, with a timeframe of after 4 weeks and a population of all enrolled subjects. Numerical primary-endpoint results are not reported in the registry record. The safety summary lists 0 of 225 participants affected by serious adverse events and 6 of 225 affected by other adverse events. Serious-event terms are not listed, and deaths are not reported.

The record lists 4 outcome measures and 0 analyses. It does not report a statistical plan, missing-data methods, or a comparative control group. Consequently, the posted information describes the design and safety counts but does not permit quantitative interpretation of the primary irritation response.