Study to Determine Skin Irritation Potential of an Antifungal Cream Containing Trolamine After Repeated Skin Application (Cumulative Irritation Patch Test): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Determine Skin Irritation Potential of an Antifungal Cream Containing Trolamine After Repeated Skin Application (Cumulative Irritation Patch Test) (NCT04531813), a na phase 3 study. The primary outcome is Cumulative Irritation Total (CIT) Score.

2. Clinical Question

This is a repeated-application skin irritation assessment, not a randomized comparison of treatment groups. Its central statistical question is descriptive: what cumulative erythema score was recorded at the butenafine test site across the participants included in the endpoint? The positive and negative control sites provide context within the test procedure, but the record does not report their numerical results or a formal comparison among sites.

The study was registered under the condition Hypersensitivity. That label does not change the stated endpoint, which is an erythema score, and does not establish that participants experienced a particular level of irritation. The posted record identifies the intended measurements and the endpoint population, but without the numerical score or participant-level results, it cannot establish the distribution of reactions across participants.

3. Trial Design

The study is titled as a cumulative irritation patch test and is recorded as completed. It is listed as Phase 3, with an enrollment of 32. The recorded start date is 2013-06-10 and the primary completion date is 2013-07-01. These administrative details describe the registry entry; they do not by themselves explain the statistical design or establish how the results were analyzed.

The design is identified as single-group, with allocation recorded as NA and masking recorded as none. Each participant received butenafine HCl 1% cream at an investigational-product test site, 0.3% sodium lauryl sulfate at a positive-control site, and a blank patch at a negative-control site. Patches were applied to skin on the upper back, between the shoulder blades. The intervention description specifies daily application excluding weekends for 21 days, or 15 applications.

Because the three sites were part of the same participant’s test procedure, this is not a randomized comparison between independent treatment arms. The registry also cautions that the arms are not a like-for-like control comparison. The sodium lauryl sulfate and blank patch serve as designated controls within the test, but the record does not provide numerical control-site results or details of a statistical contrast involving those sites.

The brief study description says researchers assessed the skin for redness, dryness, and other reactions. The primary endpoint description focuses on erythema scoring at the investigational-product site. Details beyond these descriptions—including the exact assessment schedule, procedures for handling incomplete observations, and any formal statistical plan—are not reported in the registry record. The enrollment figure should not be confused with the number included in the endpoint description: the record says endpoint data are reported for 30 participants as a group, without explaining the difference.

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 32 participants were enrolled in the study and 31 received study treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects who received treatment and completed the 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.

6. Primary Endpoint

The registry lists the primary outcome as Cumulative Irritation Total (CIT) Score, measured over 21 days.

The primary endpoint is the Cumulative Irritation Total (CIT) Score, recorded over a timeframe of 21 days. Before each patch application and after the final patch removal, investigators evaluated test sites for visible erythema using a scale from 0, meaning no visible erythema, to 4, meaning severe erythema. The scale also includes intermediate categories for slight, mild, moderate, and marked erythema. These ordered categories describe the observed redness at an assessment.

For each participant completing the study, the investigational-product erythema scores were totaled; the participant totals were then added to produce the reported CIT. The endpoint therefore accumulates scores across assessments and participants rather than reporting a single assessment or an average participant score. The registry describes the endpoint data as being reported for all 30 participants as a group.

A cumulative score is used to represent repeated observations across the application period. In general, it can reflect the accumulation of recorded erythema scores over time, while a single observation would capture only one assessment. The total alone, however, does not show how scores varied among participants or across visits. The numerical CIT result is not reported in the registry record, nor are individual scores or a distribution. Therefore, the endpoint definition is available, but the recorded level and spread of the endpoint cannot be interpreted from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint summarize?

The CIT score combines repeated erythema assessments at the investigational-product site. Investigators assigned a score at assessments before patch application and after the final patch removal, using an ordered scale that ranges from no visible erythema to severe erythema. For each completing participant, the scores were added; those participant totals were then added together. This produces a cumulative total, not an average score per participant or a score at a single visit.

In general, a cumulative endpoint can summarize the amount of recorded observation across a repeated-assessment period. It can also be affected by how many observations contribute to the total. The registry does not report participant-level scores, the distribution of scores, or a per-participant summary, so those aspects cannot be evaluated. The numerical CIT result itself is not reported in the registry record.

What does a score scale tell the reader?

The erythema scale gives ordered categories for visible redness: 0 is no visible erythema, 0.5 is slight and barely perceptible erythema, 1 is mild erythema, 2 is moderate erythema, 3 is marked erythema, and 4 is severe erythema. In general, an ordered scale conveys rank and category, but the numerical labels do not necessarily mean that the distance between adjacent categories is equal. Adding scores is the endpoint procedure specified in this record, but the resulting total should not be read as a direct measure of an equal-interval physical quantity.

The description says the total is generated by adding the erythema scores for each participant and then adding those totals. A pooled sum can depend on the number of participants and the observations contributing to it. A mean, median, range, or participant-level distribution could answer different descriptive questions, but none of those summaries is reported for this endpoint in the registry record.

What can the single-group design establish?

The record describes one group receiving the test procedure, with three test sites on participants: investigational product, positive control, and negative control. This is not a randomized comparison between treatment groups. In general, a randomized between-group comparison is designed to estimate a contrast between groups while using random assignment to address systematic differences between them. That is not the design.

The positive-control site uses 0.3% sodium lauryl sulfate, which the study description identifies as known to cause skin irritation. The negative-control site is covered with a blank patch. These sites can provide context within the test procedure, but the registry does not report their numerical outcomes or any formal comparative analysis. The design label and control-site descriptions should not be interpreted as evidence that the controls behaved in a particular way.

How should uncertainty be understood?

In general, a point estimate is a summary of observed data, while a confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. A p-value, when used, addresses how compatible data are with a specified statistical model or null hypothesis; it does not measure the size or importance of an effect. Neither a confidence interval nor a p-value for the CIT endpoint is reported in the registry record. With no numerical endpoint estimate, its precision cannot be described.

Likewise, a total score without participant-level information does not reveal heterogeneity. In general, participants can contribute differently to a pooled sum, and the same total can be formed by different patterns of individual observations. The record does not provide enough information to characterize those patterns. The endpoint description states that data are reported for 30 participants as a group, but the participant-level values and variation are not reported.

What analysis details are available?

The registry describes the endpoint calculation and the population as subjects who received treatment and completed the study. It does not report a statistical analysis plan, a model, an inferential test, a confidence interval, or a missing-data method. The study title and Phase 3 designation do not supply those missing methods. Nor does the record report a sample-size justification. It is not appropriate to infer a prespecified hypothesis, an interim analysis, or an analysis adjustment from the design description alone.

General statistical planning illustrations, when displayed, are distinct from the trial’s observed results and its original design justification. They cannot be treated as observed power or as evidence that the study was designed around a particular target unless the registry reports that. The enrollment of 32 is a recorded study count; the basis for choosing that enrollment is not reported in the registry record.

Overall, the available methods description supports a clear account of the scoring procedure and the single-group test arrangement. It does not support quantitative interpretation of the endpoint, estimation of uncertainty, or conclusions about between-site differences. Those require numerical results and analysis details that are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome measure: the Cumulative Irritation Total (CIT) Score over 21 days. The record does not describe a multiplicity strategy, such as how several endpoints or statistical tests would be handled together. No inferential analyses are listed for the outcome. Because no p-values or formal tests are reported, there is no reported multiplicity adjustment to interpret. Details about whether additional outcomes were prespecified or analyzed are not reported in the registry record.

The primary endpoint population is described as subjects who received treatment and completed the study. The endpoint description says results are reported for all 30 participants as a group, while enrollment is recorded as 32. The reason for the difference is not reported in the registry record. The record does not state whether any observations were missing, how incomplete assessment sequences were handled, or whether participants with partial data were included in any calculation.

In general, missing-data methods matter because the way incomplete observations are handled can affect a summary based on repeated measurements. A complete-case endpoint and an endpoint that uses partial records may represent different sets of observations. The registry does not specify which procedures, if any, were used beyond describing the endpoint population as study completers. It is therefore not possible to determine whether missing data occurred or to assess their possible influence.

The record does not report a statistical analysis plan, an analysis population beyond the stated endpoint population, or sensitivity analyses. It also does not explain the distinction between enrolled participants and the endpoint count. These gaps should be treated as unreported information, not as evidence for a particular exclusion, imputation, or analysis decision.

11. 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.

Most frequent non-serious adverse event terms

The adverse-event record lists 32 participants at risk for serious adverse events and 0 affected. It lists 32 participants at risk for other adverse events and 1 affected. The death count is 0, and no serious adverse-event terms are listed. These are the registry’s reported counts for the Cumulative Irritation Test group.

These fields are distinct from the primary CIT endpoint. The serious adverse-event count does not provide a numerical erythema score, and the count for other adverse events does not identify the nature of the event in the information. The record does not give further event descriptions, timing, attribution, or participant-level detail. The endpoint population refers to 30 participants, while the adverse-event fields list 32 at risk; the record does not explain the difference in these counts.

In general, an adverse-event count is a descriptive safety summary for the stated reporting category. A count of zero serious adverse events in the registry record should be read as the reported count for this study, not as proof that no skin reactions of any kind occurred. Skin erythema was separately measured using the CIT endpoint, and its numerical result is not reported in the registry record. These safety counts therefore cannot resolve the missing endpoint information or support conclusions beyond the recorded counts.

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

The record establishes that a repeated-application skin test was conducted and describes how the primary endpoint was defined. Participants received butenafine HCl 1% cream at an investigational-product site, alongside a 0.3% sodium lauryl sulfate positive-control site and a blank-patch negative-control site. The endpoint sums erythema scores across assessments and participants who completed the study. The record says endpoint data are reported for 30 participants as a group.

However, the numerical CIT total is not reported in the registry record. This means the posted endpoint description does not show the level of cumulative erythema recorded. It also does not show participant-to-participant variation, the course of scores over visits, or numerical results at either control site. Without those results, the endpoint cannot be characterized as low, high, or otherwise relative to the scoring scale.

The design is single-group and is not a randomized comparison between treatment arms. The registry specifically cautions that the arms are not a like-for-like control comparison. The presence of positive and negative control sites in the test procedure does not by itself provide a reported comparative estimate. No statistical analysis, confidence interval, or p-value for the primary outcome is reported.

The adverse-event fields report 0 serious adverse events among 32 at risk, 1 other adverse event among 32 at risk, and 0 deaths. These counts are separate from the CIT endpoint and do not replace its missing numerical result. The record does not provide further detail about the other adverse event or explain why the endpoint description refers to 30 participants while the enrollment and safety at-risk counts are 32.

Accordingly, the registry supports an account of the study procedure, the scoring system, and the recorded event counts, but not a quantitative conclusion about cumulative skin irritation. The difference between available information and missing information is important: an endpoint definition explains what investigators intended to measure, while an endpoint result is needed to describe what they observed. The latter is not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a repeated-measures endpoint and a simple between-group contrast. The CIT score is built from erythema assessments collected across repeated applications, with each participant’s scores combined and participant totals then added. That construction means the endpoint is a pooled cumulative score, rather than a single visit result or an average response. Understanding how the endpoint is assembled is essential to interpreting what its eventual value would represent.

The test procedure also illustrates why design descriptions matter. Participants had investigational-product, positive-control, and negative-control sites, but the trial is recorded as single-group and not as a randomized comparison. The registry warns that the arms are not like-for-like control comparisons. A reader should therefore distinguish within-participant test sites from independently randomized treatment groups, and should not infer a causal contrast from the presence of controls alone.

The record further highlights the difference between an endpoint definition and an endpoint result. The scoring scale and aggregation rule are described, but the numerical CIT is not reported. Without that value, and without participant-level summaries or uncertainty estimates, no quantitative interpretation of the observed outcome is possible. The registry’s enrollment and endpoint counts also differ, with no explanation recorded; this makes transparent reporting of analysis populations and incomplete data particularly relevant.

These features matter for biostatisticians and clinical researchers because a precise description of design, outcome construction, and analysis population is necessary to assess what a study can answer. Here, the available information clarifies the measurement procedure but leaves the primary numerical result and several analysis details unreported. Recognizing that boundary prevents a study’s title, phase designation, or control-site structure from being mistaken for evidence about the magnitude or precision of its endpoint.

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 posted results is that the numerical Cumulative Irritation Total score is not reported in the registry record. Although the endpoint definition is detailed, no value, participant-level distribution, or measure of variation is given. The result therefore cannot be placed on the erythema scale or assessed for consistency across participants.

The registry says that endpoint data are reported for 30 participants as a group, while enrollment is 32 and the safety fields list 32 participants at risk. The reason for the difference is not reported in the registry record. The record also does not explain how the endpoint population was formed beyond identifying subjects who received treatment and completed the study. Reasons for any difference between counts must not be inferred.

The study is single-group, with multiple test sites, and the registry states that this is not a randomized comparison and that the arms are not like-for-like. Numerical results for the positive-control and negative-control sites are not reported in the registry record. Consequently, the posted information does not permit a numerical comparison of the sites.

Statistical analysis details are limited. The record does not report an analysis plan, inferential test, confidence interval, p-value, handling of missing observations, or sample-size justification. The endpoint description explains addition of scores but does not provide participant-level information that would show how the total was distributed. The adverse-event fields also contain limited detail: one other adverse event is recorded, without further description in the information available. These limitations restrict interpretation to the stated design and reporting counts rather than the magnitude, precision, or distribution of the primary outcome.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Determine Skin Irritation Potential of an Antifungal Cream Containing Trolamine After Repeated Skin Application (Cumulative Irritation Patch Test) — NCT04531813.
• Registry record last updated 2020-09-25; status last verified 2020-09.
• 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

NCT04531813 is a completed, Phase 3, single-group cumulative irritation patch test sponsored by Bayer. It recorded enrollment of 32 and assessed butenafine HCl 1% cream at a skin site, with 0.3% sodium lauryl sulfate as a positive control and a blank patch as a negative control. Applications were described as daily excluding weekends over 21 days, or 15 applications.

The primary endpoint was the Cumulative Irritation Total (CIT) Score, formed by adding erythema scores for each completing participant and then adding participant totals. The registry describes endpoint data for 30 participants as a group, but does not report the numerical CIT score or explain the difference from enrollment. Serious adverse events were reported for 0 of 32 at risk; other adverse events were reported for 1 of 32, and deaths were 0. Further statistical analysis details are not reported in the registry record.