A Study of Crisaborole Ointment 2% in Adult Japanese Healthy Subjects and Adult Japanese Subjects With Mild To Moderate Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Crisaborole Ointment 2% in Adult Japanese Healthy Subjects and Adult Japanese Subjects With Mild To Moderate Atopic Dermatitis (NCT03260595), a randomized phase 1 study. The primary outcome is Cohort 2: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a Phase 1, single-center, randomized, vehicle-controlled, parallel-cohort study. The registry record describes triple masking, but does not identify which participant, investigator, or other roles were masked. It also does not report the randomization procedure or the allocation ratio. The study was conducted in adult Japanese participants, with healthy subjects in Cohort 1 and subjects with mild to moderate atopic dermatitis in Cohort 2.

The two cohorts had different purposes. Cohort 1 was intended to evaluate the skin irritation potential of crisaborole ointment 2% in healthy subjects. Cohort 2 was intended to evaluate safety, tolerability, and pharmacokinetics in subjects with atopic dermatitis. This distinction matters: the cohorts do not represent a single population answering one unified treatment question. The Cohort 2 safety comparison is the focus of the primary outcome, while the Cohort 1 safety counts and Cohort 2 pharmacokinetic outcomes address additional questions.

Total enrollment was 32. The registry record reports a study start date of 2017-09-13, a primary completion date of 2017-11-27, and a completed status. It does not report the number assigned to each treatment at the point of randomization, a participant flow account, or reasons for withdrawal. The reported safety groups list 20 participants at risk in the combined Cohort 1 group, 10 in the Cohort 2 crisaborole group, and 2 in the Cohort 2 vehicle group.

The design is parallel rather than crossover: the record identifies parallel cohorts and does not report a within-participant sequence of treatments. A vehicle comparator can help distinguish observations associated with the ointment formulation from those occurring in the comparison group, but interpretation depends on how participants were allocated and followed. Further operational details, including how treatment was applied and how skin irritation was assessed, 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 analysis population included all participants who received at least one dose of study medication. Data for this outcome measure was not planned to be collected and analyzed for Cohort 2, as pre-specified in protocol.

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 analysis population included all participants who received at least one dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Cohort 2: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs), measured over Baseline up to Day 36.

The primary endpoint is the number of Cohort 2 participants with treatment-emergent adverse events (AEs) and serious adverse events (SAEs), measured from baseline up to Day 36. The safety analysis population includes participants who received at least one dose of study medication. An AE is defined as an untoward medical occurrence after receiving study drug, without requiring a judgment that the drug caused it. An SAE is an AE associated with specified serious outcomes or considered significant for another reason. Treatment-emergent events are those that were absent before treatment or worsened relative to the pretreatment state, occurring between the first dose and up to 28 days after the last dose. AEs include both serious and non-serious events.

Counting participants with events is a straightforward way to describe how many people in each safety group had at least one event during the stated observation period. It is useful for an initial safety description because it focuses on participants rather than the total number of event episodes. However, a participant count does not describe event severity beyond the separate serious-event classification, event duration, recurrence, or causal attribution. Those details require additional outcome information. The registry record does not report event-level descriptions for the non-serious events in the primary endpoint.

The endpoint is descriptive in form: it asks for counts of participants with events. The registry record lists no inferential analysis for this outcome, so the posted counts alone do not establish a statistically tested difference between treatment groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as randomized, triple-masked, vehicle-controlled, and parallel-cohort. These terms describe important aspects of trial design, but the registry record does not report the operational details. Randomization uses an assignment process intended to reduce systematic differences between groups. Masking is intended to limit the influence of knowledge about assigned treatment on participants’ experience, care, or outcome assessment. The record does not specify the randomization method, allocation ratio, or which roles were masked, so those design features cannot be assessed in more detail.

What the endpoint counts

The primary outcome is a participant count: whether a participant had a treatment-emergent AE or SAE during the stated period. The definition includes events that arose after the first dose and up to 28 days after the last dose, with the outcome timeframe given as baseline up to Day 36. An event is considered treatment-emergent if it was absent before treatment or worsened relative to the pretreatment state. This timing rule identifies events by when they occurred, not by whether the study team judged the treatment to be their cause.

Counting participants with at least one event is different from counting every event episode. If one participant experiences several events, a participant-level count still records that person as a participant with an event. The posted endpoint counts therefore do not, on their own, indicate the total number of event episodes, their duration, or whether the same participant experienced multiple events. The registry record does not report those details for the non-serious events.

How to read the group counts

The reported at-risk count is the group denominator for the posted safety count. In Cohort 2, the crisaborole group has 10 at risk and 9 participants with other AEs; the vehicle group has 2 at risk and 2 participants with other AEs. The listed SAE counts are zero in both groups. Cohort 1 reports 20 at risk in a combined crisaborole ointment 2% and vehicle group, with no participants listed as having serious or other AEs. Because the Cohort 1 treatments are combined, the record does not allow a treatment-specific count for that cohort.

For binary outcomes such as whether a participant had an event, uncertainty can be expressed with a confidence interval around an estimated event frequency or group contrast. In general, a confidence interval gives a range of values compatible with the data under the method used; it does not guarantee that the true value lies within that particular interval. Small groups tend to yield imprecise estimates, and zero observed events do not imply zero underlying risk. No confidence intervals or formal tests for the primary outcome are reported in the registry record.

What a comparison would require

A comparative analysis would need to define a measure of contrast between treatment groups and account for the uncertainty arising from the observed counts. General approaches for binary outcomes include comparing event proportions or modeling the probability of an event. The appropriate approach depends on the design, the analysis population, group sizes, and prespecified statistical plan. The registry record does not report a specific comparison measure, model, test, covariate adjustment, or analysis plan for this outcome. No adjusted or unadjusted treatment effect is listed.

When groups are very small, standard methods that rely on large-sample approximations can perform poorly. Exact methods are one general alternative for sparse binary data, though the record does not say that an exact method was used. A method should be selected and interpreted in the context of the trial plan; it should not be inferred from the counts alone. The registry record does not report any method for handling the small Cohort 2 vehicle group.

Other registered measures

The record lists pharmacokinetic outcomes in Cohort 2, including maximum observed plasma concentration, time to maximum concentration, and several measures of area under the plasma concentration-time curve. These measures characterize drug and metabolite concentrations over time. Accumulation ratios are also listed. Such measures address exposure and concentration patterns, rather than the participant-level AE count. Their presence does not supply a statistical method for the primary safety endpoint. The registry record does not report pharmacokinetic results in the registry record used for this analysis.

Thirteen outcome measures are listed, while no analyses are listed. The record does not provide the statistical analysis plan, the method used to summarize each outcome, or any interim-analysis procedure. A sample-size calculation for the primary endpoint is not reported in the registry record. The general planning illustration described for the posted results is not the trial’s own design justification and does not establish observed power. In general, planning calculations concern the assumptions for a future or planned study; they are not evidence that a completed study had adequate precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 13 outcome measures spanning safety, tolerability, skin irritation, and pharmacokinetics. When a study assesses multiple outcomes or multiple measures, the chance of at least one apparently unusual result can increase if many statistical tests are conducted. General methods for addressing multiplicity include identifying a primary outcome in advance, ordering hypotheses, or adjusting inferential thresholds. The registry record does not report a multiplicity strategy or a family of hypothesis tests. It lists no analyses, so there is no reported set of inferential results to evaluate for multiplicity.

The primary outcome is defined as a participant count over a specified period, but the record does not report a missing-data method for that outcome. It does not state how participants with incomplete follow-up, missing event assessments, or unknown outcome status were handled. The safety analysis population is described as including participants who received at least one dose of study medication. This definition identifies who is eligible for the safety summaries, but it does not explain how missing observations within that population were treated.

The registry record does not report an intention-to-treat population, a per-protocol population, or an analysis set for the Cohort 2 pharmacokinetic outcomes. It also does not report exclusions after enrollment, withdrawals by group, adherence, or the amount of missing data. These omissions limit assessment of whether the listed counts include all participants who began treatment and whether observation time was comparable across groups.

Missing-data methods can influence results when the probability of an unrecorded outcome is related to participants’ health or treatment experience. In general, complete-case summaries describe participants with recorded outcomes, while imputation methods make additional assumptions about missing outcomes. The registry record does not say whether either approach, or another approach, was used. No assumptions about missing events or missing pharmacokinetic measurements should therefore be inferred from the posted counts.

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 safety results distinguish serious adverse events from other adverse events. In Cohort 2, the crisaborole ointment 2% group lists 0 participants with SAEs among 10 at risk and 9 participants with other AEs. The vehicle group lists 0 participants with SAEs among 2 at risk and 2 participants with other AEs. In Cohort 1, the combined crisaborole ointment 2% and vehicle group lists 0 participants with SAEs and 0 with other AEs among 20 at risk.

An SAE is defined by specified outcomes, including death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, or a congenital anomaly, as well as events judged significant for another reason. The definition does not mean that every serious event is caused by study treatment. Likewise, the AE definition explicitly does not require a causal relationship.

The zero SAE counts indicate that no SAEs were recorded in these safety groups during the reported period. They do not exclude rare events or establish that the risk of an SAE is absent. The Cohort 2 vehicle group is particularly small, so its observed count cannot provide a precise estimate of event frequency. The Cohort 1 result combines both treatments and cannot be used to distinguish their safety counts. The registry record does not report individual non-serious event terms, severity details, or attribution judgments for the primary endpoint.

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

The posted results describe adverse-event counts among participants enrolled in a small Phase 1 study, with separate aims for healthy subjects and subjects with mild to moderate atopic dermatitis. In Cohort 2, most participants in the crisaborole group and both participants in the vehicle group are listed as having other AEs, while no SAEs are listed in either group. These are observations within the recorded groups and follow-up period, not a definitive comparison of treatment-related risk.

The count of participants with an AE does not indicate how many distinct events occurred, whether events were mild or severe, how long they lasted, or whether they were judged related to treatment. The record’s definition includes events without regard to the possibility of a causal relationship. The absence of SAEs in the listed groups is also a limited observation: it does not rule out uncommon serious events that a study of this size may not capture.

The separate cohorts should not be merged into one treatment comparison. Cohort 1 involved healthy subjects and is reported with crisaborole and vehicle combined; Cohort 2 involved subjects with atopic dermatitis and has separate treatment-group counts. The study’s stated Cohort 1 aim was skin irritation potential, while Cohort 2 also addressed safety, tolerability, and pharmacokinetics. These distinct purposes and reporting structures prevent the Cohort 1 counts from serving as a direct substitute for the Cohort 2 comparison.

The record does not report a formal statistical comparison, confidence intervals, or a statistical analysis plan for the primary endpoint. The unequal and small Cohort 2 group sizes, especially the vehicle group, make the raw counts imprecise for comparative interpretation. No conclusion about efficacy can be drawn from the primary safety endpoint. The listed pharmacokinetic outcomes concern drug exposure, but their results are not reported in the registry record used for this analysis. Overall, the results are best understood as descriptive safety information from this study rather than proof that treatment caused or prevented events.

13. Why This Trial Matters Statistically

This trial illustrates why clinical trial results need to be read in the context of their design and outcome definitions. A single Phase 1 record can have distinct cohorts with different populations and objectives: healthy subjects are studied for skin irritation potential, while participants with atopic dermatitis are studied for safety, tolerability, and pharmacokinetics. The same event count cannot automatically answer each of those questions.

It also illustrates the limits of raw counts in small groups. The Cohort 2 vehicle group has only 2 participants at risk. When a denominator is small, the status of an individual participant can strongly shape the apparent pattern. The counts are informative as a record of what was observed, but they do not give a precise estimate of how often events would occur in a broader population. No formal analysis or uncertainty interval is listed for the primary outcome.

The endpoint definition further matters. Treatment-emergent timing identifies when events occurred in relation to study treatment, but the AE definition does not require evidence that treatment caused them. Seriousness is classified separately from causality. Keeping those concepts distinct helps prevent an event count from being misread as a causal treatment effect.

Finally, the combined reporting for Cohort 1 shows how the structure of a result can limit comparisons even when a vehicle is part of the study. The record reports a combined group there, so treatment-specific safety counts cannot be recovered from those data. Statistical interpretation depends not only on whether a trial is randomized, but also on the available group-level results, outcome definitions, sample sizes, and analysis methods. Several of those methodological details are not reported in the registry record.

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 registry record provides limited detail for evaluating the primary safety comparison. It does not report the randomization procedure, allocation ratio, identities of the masked roles, or treatment assignment details. Although the study is described as randomized and triple-masked, those labels alone do not show how the procedures were implemented.

The Cohort 2 vehicle group has 2 participants at risk, compared with 10 in the crisaborole group. The resulting counts are limited in precision and cannot support a robust interpretation of uncommon events. The registry record does not explain the group-size imbalance or provide a participant flow account, withdrawals, or reasons for discontinuation. It also does not report whether follow-up duration differed among participants.

The Cohort 1 safety information is reported for crisaborole ointment 2% and vehicle together. This prevents a separate treatment-specific reading of the Cohort 1 AE and SAE counts. The Cohort 1 record therefore cannot supply a distinct vehicle comparison for the healthy-subject safety data.

Additional limitations include the absence of a reported statistical analysis plan, inferential analyses, confidence intervals, missing-data procedures, and outcome-level details for non-serious AEs. The record does not report event severity, duration, recurrence, or attribution for those events. Although pharmacokinetic outcomes are listed, their results are not included in the registry record used for this analysis. The study’s small Phase 1 setting and the short stated treatment-emergent observation window also constrain how broadly the safety counts can be interpreted. Further details about treatment administration and skin irritation assessment are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Crisaborole Ointment 2% in Adult Japanese Healthy Subjects and Adult Japanese Subjects With Mild To Moderate Atopic Dermatitis — NCT03260595.
• Registry record last updated 2019-03-01; status last verified 2018-10.
• Results first posted 2019-03-01.
• 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 NCT03260595, a completed Phase 1, single-center, randomized, triple-masked, vehicle-controlled, parallel-cohort study of crisaborole ointment 2% in adult Japanese participants. Total enrollment was 32. Cohort 1 included healthy subjects and assessed skin irritation potential; Cohort 2 included subjects with mild to moderate atopic dermatitis and assessed safety, tolerability, and pharmacokinetics.

The primary endpoint was the number of Cohort 2 participants with treatment-emergent AEs and SAEs from baseline up to Day 36. The posted Cohort 2 counts list 9 participants with other AEs among 10 at risk in the crisaborole group and 2 among 2 at risk in the vehicle group; no SAEs are listed in either group. Cohort 1 reports no serious or other AEs in a combined group of 20 participants. No inferential analyses are listed, and key analysis, missing-data, and randomization details are not reported in the registry record.