A Study to Determine the Safety & Efficacy of ZPL-5212372 in Healthy Subjects and in Subjects With Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Determine the Safety & Efficacy of ZPL-5212372 in Healthy Subjects and in Subjects With Atopic Dermatitis (NCT02795832), a randomized phase 1, phase 2 study. The primary outcome is Percent Change From Baseline in EASI Score in Cohort 3.

2. Clinical Question

At a broad level, the study asks whether the topical treatment can be evaluated for safety and pharmacokinetics in healthy volunteers and patients, and for efficacy in the atopic dermatitis population. The Cohort 3 endpoint makes change in eczema severity the main stated efficacy measure. The registry also lists secondary outcomes involving EASI response thresholds, investigator assessment, pruritus, patient global impression and body surface area. Those listed measures describe additional questions, but their numerical results are not reported in the registry record.

3. Trial Design

The registry describes a randomized, parallel-group, placebo-controlled study with quadruple masking. It lists Phase 1 and Phase 2 and reports an enrollment of 53. The trial is marked completed; the start is recorded as 2016-06 and the primary completion date as 2017-03-01. The official title describes topical treatment for up to 2 weeks in healthy subjects and subjects with atopic dermatitis. The brief summary additionally describes an adaptive design and sequential groups. Details of how adaptation or sequencing operated are not reported in the registry record.

The intervention groups received ZPL-5212372 1% w/w ointment twice daily or placebo ointment twice daily. The registry names three cohorts, with active-treatment and placebo arms within each. It does not state the number randomized to each arm or cohort in the general trial description. Nor does it give a detailed account of allocation concealment, masking procedures, adherence monitoring, or the handling of participants who discontinued treatment.

The registry identifies the primary endpoint as percent change from baseline in EASI score in Cohort 3, assessed on Day 1 and Day 14. Its listed analysis population is the Full Analysis set. Secondary outcomes include EASI-50 and EASI-75 responders, investigator global assessment, change in pruritus numerical rating scale, patient global impression of change, and change in body surface area. Several of these are specified for Cohort 3. The stated study objectives also include safety, tolerability and pharmacokinetics, but detailed numerical pharmacokinetic results are not reported in the registry record.

The registry lists 10 outcome measures and 14 analyses. These counts indicate multiple recorded outcomes or analyses, but do not establish how the investigators prioritized, adjusted or interpreted them. The protocol, original sample-size justification, analysis plan, and details of any interim decision process are not reported in the registry record. The enrollment figure describes the study overall; it should not be treated as the number analyzed for the Cohort 3 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis set

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: Full analysis set

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline in EASI Score in Cohort 3, measured over Day 1 and Day 14.

The primary endpoint is percent change from baseline in EASI score in Cohort 3, with Day 1 and Day 14 identified as the assessment timeframe. EASI, the Eczema Area and Severity Index, combines assessments of eczema severity and the extent of affected skin across four body regions: head and neck, arms, trunk, and legs. Each region contributes according to its stated body-area weight. Severity is graded from none to severe, while the extent grade represents the estimated proportion of skin involved. The resulting EASI score can range from 0 to 72; higher scores indicate more severe disease.

EASI is used to represent both the intensity of eczema signs and how much body surface is affected, rather than relying on a single symptom or one body region. A change from baseline can therefore describe how the combined score differs between the initial and later assessments. Expressing change as a percentage relates that change to the baseline score, though interpretation depends on the calculation convention and the observed values. The registry record does not report those values or define further calculation details.

The endpoint is specified as a mean, with standard error as the dispersion measure. A mean summarizes the group’s average endpoint value; standard error describes the precision of that estimated mean, not the spread of individual participant scores. The registry record does not provide the arm-level means, standard errors, treatment contrast, or uncertainty interval. Without them, the direction, size and precision of any Cohort 3 difference cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The listed primary measure is continuous: it is a mean of percent change in EASI score. The registry identifies standard error as its dispersion summary. Those choices describe the form of the outcome and one aspect of uncertainty, but do not fully specify the statistical model or the comparison used to answer the trial question. Details of the analysis model, covariate adjustment and estimation procedure are not reported in the registry record.

What does a mean describe?

A mean is the arithmetic average of the observations included in a group or analysis. For a continuous outcome, it gives a concise measure of the group’s central level. It does not show whether individual observations cluster closely around that average or vary substantially. In this trial, the endpoint is described as the mean percent change from baseline in EASI in Cohort 3. The actual mean values for the treatment groups are not reported in the registry record, so the group averages and their difference cannot be narrated.

Percent change expresses a change relative to a baseline value. This can make changes more interpretable when starting scores differ, but the meaning depends on the exact calculation and on baseline values. The registry identifies the measure as percent change from baseline but does not give a fuller calculation definition or the numerical results. No direction of change should be inferred from the endpoint label alone.

What does standard error describe?

Standard error describes the precision of an estimated mean. In general, a smaller standard error indicates that the mean is estimated more precisely, while a larger one indicates less precision. It is not the same as the standard deviation, which describes variation among individual observations. The primary outcome description names standard error, but the actual standard errors are not reported in the registry record. Thus, the precision of the group means cannot be assessed from the endpoint description.

A treatment comparison is usually expressed as an estimated contrast between groups, accompanied by an uncertainty measure. A confidence interval is a general way to communicate uncertainty around an estimate: it identifies a range of values that are reasonably compatible with the data and the stated method. A p-value, in general, measures how surprising data at least as incompatible with a specified null hypothesis would be under that hypothesis and the chosen analysis. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. Neither should be reconstructed without the required numerical results and analysis details.

Why can group differences be uncertain?

Randomized comparisons can still be imprecise, particularly when the analyzed groups contain limited information. The total enrollment is 53, but the Cohort 3 sample size and the number included in its primary analysis are not reported in the registry record. It is therefore not possible to infer the precision of the Cohort 3 estimate from the overall enrollment alone. Baseline characteristics, outcome variability and missing observations can also affect precision; these details are not reported for the primary comparison.

The registry calls the design adaptive and sequential-group in its brief summary. In general, an adaptive design may use accumulating information to guide prespecified changes, and sequential groups may be enrolled or assessed in stages. Those terms do not establish which adaptations were allowed, what decision rules applied, or how error rates were controlled. Those design and analysis details are not reported in the registry record. The official title describes a randomized, double-blind, placebo-controlled study, while the brief summary describes it as double-blind with a third party open. The record does not explain the masking arrangements in greater detail.

How should planning figures be interpreted?

Planning calculations can illustrate the sample size needed under assumptions about the effect to detect, variability, allocation and statistical method. The registry’s planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation. It considers an effect that is a stated fraction of the observed effect. These are planning assumptions, not a report of the trial’s original design rationale. The sample-size justification used to plan the trial is not reported in the registry record.

Such calculations describe hypothetical future planning under the chosen assumptions. They are not observed power, and they do not show that the completed study had a particular probability of detecting an effect. The actual result and its uncertainty remain essential for interpretation. Because numerical primary outcome results are not reported in the registry record, no observed treatment effect or confidence interval can be used to evaluate the stated planning illustration.

More generally, statistical methods should match the outcome and design. For a continuous measure, analysis might account for baseline score, cohort structure or repeated measurements, but the use of any particular approach cannot be presumed. The registry record does not report whether the primary endpoint was analyzed with adjustment, how repeated assessments were handled, or whether an alternative analysis was prespecified. These omissions limit the ability to reproduce or fully evaluate the primary comparison from the registry description.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and 14 analyses. The primary endpoint is percent change from baseline in EASI in Cohort 3. Listed secondary outcomes cover EASI-50 and EASI-75 responders, investigator global assessment, pruritus, patient global impression of change and body surface area. Multiple outcomes and analyses create multiple opportunities to observe results that appear notable by chance. In general, prespecifying a primary question and applying a planned approach to multiplicity can help distinguish confirmatory findings from exploratory ones. The registry record does not report a multiplicity adjustment, a testing hierarchy, or which secondary analyses were confirmatory.

The primary endpoint names the Full Analysis set. The registry record does not define membership in that population, describe how participants were handled after randomization, or say whether the analysis followed an intention-to-treat principle. It also does not report the number analyzed in Cohort 3. The overall enrollment of 53 should not be substituted for a cohort-specific analysis denominator.

Missing-data handling matters because incomplete outcome records can affect both the estimate and its uncertainty. The number of missing Day 1 or Day 14 assessments, reasons for missingness, and methods used to address missing values are not reported in the registry record. The record also does not report sensitivity analyses assessing how different assumptions about missing outcomes might affect the findings.

The listed secondary outcome for change in pruritus is described as an observed-case analysis. In general, an observed-case analysis uses available observations at the specified assessment without filling in missing outcomes; the resulting analyzed group can differ from the group originally enrolled or randomized. The registry does not report the extent of missingness for that analysis or whether comparable approaches were used for other outcomes. The statistical analysis plan, including its treatment of multiplicity and missing data, is not reported in the registry record.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The safety record lists serious adverse events, other adverse events and deaths separately for each treatment stratum. In every listed stratum, zero serious adverse events and zero deaths are recorded. The number at risk and the number affected by other adverse events are: Cohort 1 ZPL-5212372 10% BSA, 2 at risk and 2 affected; Cohort 1 ZPL-5212372 40% BSA, 6 and 3; Cohort 1 Placebo 10% BSA, 1 and 1; Cohort 1 Placebo 40% BSA, 3 and 1; Cohort 2 ZPL-5212372 10% BSA, 2 and 2; Cohort 2 ZPL-5212372 40% BSA, 6 and 4; Cohort 2 Placebo 10% BSA, 1 and 1; Cohort 2 Placebo 40% BSA, 2 and 2; Cohort 3 ZPL-5212372, 20 and 17; and Cohort 3 Placebo, 10 and 9.

These are counts within the strata as named in the registry. They do not identify event types, severity of non-serious events, timing, duration or relationship to study treatment. The registry lists no serious adverse event terms. With limited numbers at risk in several strata, zero recorded serious events does not establish that such events cannot occur or rule out uncommon risks. The counts alone also do not provide a controlled estimate of comparative safety.

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

The registry record establishes that a randomized, placebo-controlled study of topical ZPL-5212372 was conducted and completed, and that a Cohort 3 EASI measure was designated as the primary endpoint. It also records outcomes intended to describe safety, tolerability, pharmacokinetics and additional aspects of atopic dermatitis. These design and measurement details explain what the trial set out to examine. They are not a substitute for the numerical findings.

The primary outcome result is not reported in the registry record. Without arm-specific means, a treatment contrast and its uncertainty, it is not possible to state what change was observed, how large a difference was, or how precisely it was estimated. It is also not possible to characterize the listed secondary outcomes numerically from their titles alone. The absence of posted endpoint estimates should not be interpreted as either a favorable or unfavorable result.

The safety listing records no serious adverse events and no deaths in the named groups, while recording other adverse events in each group. These observations describe what is listed for this study; they do not establish that treatment caused or did not cause events. They also do not demonstrate the absence of rare or delayed harms. Adverse-event terms, individual event details and a formal comparative safety analysis are not reported in the registry record.

More broadly, randomized design and masking can help reduce certain biases, but they do not resolve every uncertainty. Interpretation also depends on adequate outcome reporting, clear analysis methods, completeness of follow-up and appropriate handling of multiple outcomes. Relevant details are not reported in the registry record. The record’s description of an adaptive design does not disclose its decision rules or the analysis methods used to account for design features.

Accordingly, the defensible statistical reading is narrow: the study was designed to compare topical ZPL-5212372 with placebo and specified EASI change in Cohort 3 as its primary efficacy measure, but the posted record does not include the numerical primary result needed to estimate that comparison. It supports description of the trial’s design and recorded safety counts, not a conclusion about treatment efficacy or a complete judgment of safety.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining a randomized, placebo-controlled design with a stated adaptive, sequential-group approach and multiple objectives. Its listed aims include safety, tolerability and pharmacokinetics, alongside an efficacy endpoint in atopic dermatitis. That mixture makes clarity about populations, stages, endpoints and analysis decisions important: conclusions drawn from one cohort or outcome need not answer every study objective.

The primary endpoint uses EASI, a measure that combines severity and affected body area, and frames the outcome as percent change from baseline. This gives the trial a defined continuous efficacy measure for Cohort 3. The registry identifies a Full Analysis set and standard error as the dispersion summary, but the numerical estimates and detailed analysis methods are not reported in the registry record. A stated endpoint is useful for interpreting a study’s aims; without its result, it cannot establish the observed treatment contrast.

The record also lists multiple secondary outcomes and analyses. This makes prespecification and multiplicity handling relevant statistical considerations. The record does not report whether or how those issues were addressed, or how the adaptive features influenced analysis. The missing outcome estimates further limit comparison across the registered measures and prevent assessment of their consistency.

Finally, the safety record offers a reminder that counts must be read alongside the number at risk and the breadth of follow-up. Zero recorded serious events in the listed groups is an observation, not proof of no risk. The trial’s overall enrollment of 53 and the smaller listed strata underscore the need to consider precision and the possibility of uncommon events without converting those counts into unsupported conclusions. Taken together, the record is informative about trial structure and measurement, while its limited numerical reporting restricts statistical interpretation of efficacy and safety.

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.

A central limitation of the registry record is that it does not report numerical results for the primary EASI endpoint. The arm-level means, standard errors, treatment contrast and confidence interval or p-value are absent. The endpoint is defined, but the magnitude and precision of the comparison cannot be assessed.

The overall enrollment is 53, yet the number randomized, treated and analyzed in each cohort and arm is not reported in the general trial description. The primary endpoint names Cohort 3 and the Full Analysis set, but the cohort-specific denominator and analysis-set definition are not reported in the registry record. This prevents a direct assessment of how much information contributed to the primary estimate.

The registry’s brief summary describes an adaptive design and sequential groups, but operational details and decision rules are not reported. The statistical analysis plan, sample-size justification and approach to repeated assessments are also not reported. The record does not explain whether multiplicity was addressed across the 10 outcome measures and 14 analyses. Missing-data amounts, reasons and handling methods are not reported, apart from the description of one secondary outcome as observed case.

Safety information is limited to counts by listed stratum. Detailed event terms, timing, severity for other adverse events, exposure duration and attribution are not reported. The record also does not give numerical pharmacokinetic findings despite naming pharmacokinetics as a study objective. These gaps restrict conclusions to the trial’s documented structure and the safety counts actually listed, rather than allowing a full assessment of efficacy, safety or pharmacokinetics.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Determine the Safety & Efficacy of ZPL-5212372 in Healthy Subjects and in Subjects With Atopic Dermatitis — NCT02795832.
• Registry record last updated 2019-04-05; status last verified 2019-04.
• Results first posted 2019-04-05.
• 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

NCT02795832 is a completed randomized, placebo-controlled, parallel-group study listed as Phase 1 and Phase 2, with quadruple masking and 53 participants enrolled. It evaluated topical ZPL-5212372 1% w/w ointment applied twice daily for up to 2 weeks against placebo ointment in adult healthy volunteers and patients with moderate-to-severe atopic dermatitis. The primary endpoint was percent change from baseline in EASI score in Cohort 3 on Day 1 and Day 14, summarized as a mean with standard error in the Full Analysis set.

The registry lists 10 outcome measures and 14 analyses, as well as safety counts by treatment stratum. It records zero serious adverse events and zero deaths in the listed groups. Numerical results for the primary endpoint and detailed analysis methods are not reported in the registry record, limiting interpretation of the treatment comparison.