This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Determine the Efficacy of ZPL-3893787 in Subjects With Atopic Dermatitis (NCT02424253), a randomized phase 2 study. The primary outcome is Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02424253 |
| Phase | Phase 2 |
| Condition | Atopic Dermatitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 98 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ziarco Pharma Ltd |
| Results posted | Yes |
2. Clinical Question
Population
Adults with moderate to severe atopic dermatitis were the intended study population. The brief summary describes eligibility using an Eczema Area and Severity Index score from 12 to 48. The record reports enrollment of 98, while the study summary describes approximately 90 subjects. The primary endpoint population is the Full Analysis Set, defined as randomized subjects who received at least 1 dose of study drug.
Intervention
Participants assigned to the active arm received oral ZPL-3893787 at 30 mg once daily for 8 weeks, or 56 days. The study followed a run-in period before randomization, according to the brief summary.
Comparator
The control arm received placebo once daily for 8 weeks. The arm description specifies 1 capsule orally once daily. The registry identifies the study as placebo controlled.
Primary question
The primary question concerned change from baseline to Week 8 in the Numerical Rating Score for worst itch, also called pruritus. Participants rated their worst itch during the previous 12 hours on a scale from 0, no itching, to 10, itching as bad as can be imagined. The registry record does not report arm-level changes or an estimated between-arm contrast, so the magnitude and precision of any difference cannot be assessed from the posted primary outcome information.
3. Trial Design
This was a randomized, placebo-controlled, parallel-group Phase 2 study of oral ZPL-3893787 in adults with moderate to severe atopic dermatitis. Participants were assigned to ZPL-3893787 or placebo after a run-in period. The active regimen was 30 mg once daily for 8 weeks, described also as 56 days; placebo was given once daily for the same period. The registry records 98 participants enrolled. Its brief summary describes an approximate target of 90 subjects, which is not the same wording as the reported enrollment.
The study record lists randomized allocation and quadruple masking. The brief summary describes the study as double blind. The record does not explain which groups of people were masked or how masking was implemented, so those details are not reported in the registry record. A parallel-group design assigns participants to one study arm and follows those arms over the same study period, rather than switching participants between interventions.
The primary endpoint was change from baseline to Week 8 in the NRS for worst itch. The primary population is described as the Full Analysis Set, consisting of randomized subjects who received at least 1 dose of study drug. A secondary outcome was change from baseline in EASI score. The registry lists 2 outcome measures and 2 analyses, but the record does not provide numerical values for the primary endpoint or the secondary outcome in the information. The trial status is completed; start is recorded as 2015-05-18 and primary completion as 2016-01.
The study is identified as a Phase 2 trial sponsored by Ziarco Pharma Ltd. The registry record does not report the allocation ratio, details of the randomization procedure, study sites, or the specific procedures used to maintain masking. Those design details therefore cannot be described further.
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
| Stage | ZPL-3893787 | Placebo |
|---|---|---|
| STARTED | 65 | 33 |
| COMPLETED | 54 | 24 |
| NOT COMPLETED | 11 | 9 |
Reasons for not completing this period:
| Reason | ZPL-3893787 | Placebo |
|---|---|---|
| Other, unspecified | 1 | 0 |
| Compliance problems | 1 | 0 |
| Physician Decision | 2 | 0 |
| Lack of Efficacy | 0 | 7 |
| Adverse Event | 2 | 0 |
| Consent withdrawn by subject | 4 | 1 |
| Lost to Follow-up | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): Included all randomized subjects who received at least 1 dose of study drug.
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 (FAS): Included all randomized subjects who received at least 1 dose of study drug.
| Characteristic | Unit | ZPL-3893787 | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 65 | 33 | 98 | |
| Age, Continuous | years | 33.7 (SD 11.22) | 35.5 (SD 12.52) | 34.3 (SD 11.64) |
| Sex: Female, Male: Female | Participants | 36 | 20 | 56 |
| Sex: Female, Male: Male | Participants | 29 | 13 | 42 |
| Fitzpatrick Skin Type: Type I | participants | 2 | 4 | 6 |
| Fitzpatrick Skin Type: Type II | participants | 24 | 11 | 35 |
| Fitzpatrick Skin Type: Type III | participants | 32 | 14 | 46 |
| Fitzpatrick Skin Type: Type IV | participants | 3 | 2 | 5 |
| Fitzpatrick Skin Type: Type V | participants | 3 | 1 | 4 |
| Fitzpatrick Skin Type: Type VI | participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch), measured over Baseline to Week 8.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline to Week 8 in the Numerical Rating Score for pruritus, specifically worst itch. Participants rated the worst itching experienced during the previous 12 hours on a scale from 0, meaning no itching, to 10, meaning itching as bad as can be imagined. The assessment was made twice daily, in the morning soon after rising and in the evening before retiring, and recorded in an eDiary. If a participant posted only 1 measurement on a particular day, that score counted as the worst measurement.
This endpoint captures a symptom reported directly by participants. It focuses on itch intensity rather than a clinician-assessed skin sign, and the repeated daily ratings are intended to represent experiences across the treatment period more fully than a single isolated rating. Those are general reasons symptom scales may be used in clinical trials; they do not establish how well this particular endpoint was completed or summarized in this study.
The scale gives the numerical direction a straightforward meaning: lower scores correspond to less reported itch, while higher scores correspond to worse itch. A change score compares a participant’s score at follow-up with the baseline score. To interpret a comparative treatment result, however, arm-level change estimates and an uncertainty measure are needed. The registry record does not report those numerical primary outcome results, so the size, direction, and precision of the between-arm contrast cannot be assessed.
The primary endpoint population was the Full Analysis Set: randomized subjects who received at least 1 dose of study drug. The record does not state how missing diary entries or incomplete follow-up scores were handled in the endpoint analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary outcome as change from baseline to Week 8 in the worst-itch NRS, but it does not report the numerical outcome by arm or the estimated difference between arms. It also does not provide a confidence interval, standard error, or p-value for that contrast. As a result, the posted primary outcome information cannot establish the size or direction of the observed contrast, nor how precisely it was estimated.
This matters because the endpoint is a continuous score. A treatment comparison would ordinarily be interpreted through the estimated difference in change between the ZPL-3893787 and placebo groups, together with an uncertainty interval. The score’s scale supplies context for understanding the estimate: 0 is no itching and 10 is itching as bad as can be imagined. But without the arm results, the scale alone says nothing about the magnitude of the change observed in the trial.
The record gives an enrollment of 98 and describes a Full Analysis Set comprising randomized participants who received at least 1 dose. It does not report the number analyzed for the primary endpoint or the number with complete outcome data. The safety denominators are 65 for ZPL-3893787 and 33 for placebo, but those are safety figures and should not be treated as the primary endpoint analysis counts unless the record explicitly says so. It does not.
The study is marked completed, but completion status is not a measure of the size or reliability of the endpoint result. Nor does the existence of a primary outcome definition imply that the result itself is available in the registry record. The brief summary describes a study designed to assess itch after 8 weeks; the posted primary result values needed to quantify that assessment are not reported in the registry record.
The record also lists a secondary outcome, change from baseline in EASI score, without numerical results in the material reported. Thus, a comparison of itch and skin-severity findings cannot be made. No inference about treatment effectiveness should be drawn solely from the study design, enrollment, or endpoint description. The statistically appropriate conclusion is limited: the registry identifies the question and measurement approach, but the posted data do not permit an estimate of the primary treatment contrast or its precision.
9. Statistical Methods Explained
The primary measure is continuous: it is a score on a numerical scale, and the registry identifies the endpoint summary as a mean with standard deviation. In general, a mean describes the central value of observations, while a standard deviation describes how spread out individual observations are around that mean. They answer different questions. A similar mean can occur in groups with very different variability, and variability affects how precisely a group summary and a between-group comparison can be estimated.
What a change score represents
In general, a change score expresses how a measurement differs from its baseline value by the specified follow-up time. For this trial, the defined interval is baseline to Week 8. Since the NRS ranges from 0 for no itching to 10 for itching as bad as can be imagined, a lower score represents less reported itch. To compare arms, investigators would need to report the change in each arm and a clearly defined contrast between those changes, or report an adjusted comparison. The registry record does not provide those numerical results, and the method used to estimate the arm contrast is not reported in the registry record.
Uncertainty and confidence intervals
In general, a confidence interval gives a range of values compatible with the observed data under the analysis model and expresses uncertainty in an estimate. A narrow interval indicates greater precision than a wide interval, all else being equal. It is not a guarantee that the true effect lies in the interval, and it does not by itself say whether a result is clinically important. No confidence interval for the primary endpoint comparison is reported in the registry record. Without one, the precision of any primary comparison cannot be assessed from the posted information.
A p-value, in general, describes how unusual data at least as discrepant as those observed would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure effect size. The registry record does not report a primary-endpoint p-value or enough numerical outcome information to reconstruct one. The record’s planning description mentions a two-sided significance level of 0.05 for sample-size illustrations; that planning assumption is not a reported p-value or evidence about the trial result.
Sample-size illustrations
The registry record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not the trial’s own documented design justification. The actual fraction and numerical sample-size illustrations are not reported in the registry record presented in this analysis. The record does not report the sponsor’s sample-size justification, so no claim can be made about the reasoning behind the enrollment target.
In general, a sample-size calculation estimates how many participants would be needed under specified assumptions to detect an effect with a chosen probability, often called power. Such a calculation depends on the assumed effect, variability, significance level, allocation, and analysis method. If the assumed effect is smaller, more participants are generally needed to distinguish it from random variation, all else being equal. A planning illustration based on an observed effect is not observed power and does not show that the completed trial had a particular probability of detecting an effect. It cannot substitute for reporting the actual estimate and its uncertainty.
Why variability and model choice matter
For a continuous outcome, the spread of participant scores contributes to uncertainty in the group comparison. General statistical practice may use a model to account for baseline values or other prespecified factors, but the statistical model, covariates, and adjustment strategy used for this trial are not reported in the registry record. The record identifies a mean and standard deviation for the endpoint, but does not provide the corresponding outcome values. A distribution may also have features such as skewness or unusual observations; whether those arose in this trial is not reported.
When data are more variable than a model assumes, estimated uncertainty can be too small if the analysis does not account for that extra variability. This is a general concern, not a finding about this study. Over-dispersion is especially relevant to count data, where observed variation exceeds a model’s expectation; the primary endpoint is a continuous itch score, and the record does not report evidence of over-dispersion or describe a model that would require such an assessment.
The trial’s endpoint was measured repeatedly through eDiary assessments, but the registry record does not state how repeated observations were combined to form the Week 8 outcome or how within-participant correlation was addressed. It would be inappropriate to assume that daily scores were averaged in a particular way, or that a particular repeated-measures model was used. The score rule for a day with only 1 measurement is reported; broader rules for incomplete diary data are not.
The registry lists the Full Analysis Set as randomized subjects who received at least 1 dose. This specifies who was intended to be included under that population definition, but does not disclose the number analyzed, the handling of missing scores, or whether other analysis populations were used. The statistical analysis plan and any interim analyses are not reported in the registry record. Consequently, the methods that can be described are limited to the outcome definition, its summary as a mean with standard deviation, the stated population definition, and the separate planning assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome of change from baseline in worst-itch NRS and a secondary outcome of change from baseline in EASI score. It also indicates 2 outcome measures and 2 analyses. The record does not report a multiplicity strategy, such as whether testing was hierarchical, whether the outcomes shared an error-rate adjustment, or whether the secondary outcome was treated as exploratory. Without that information, the family of hypotheses and the interpretation of any multiple tests cannot be reconstructed. No primary or secondary outcome p-values are reported in the information.
The record defines the Full Analysis Set as randomized subjects who received at least 1 dose of study drug. That definition does not reveal the number of participants with usable Week 8 measurements, how many were excluded from an analysis, or why any data may have been unavailable. Missing-data methods, including any imputation, model-based handling, or sensitivity analyses, are not reported in the registry record. The handling of missing diary entries beyond the rule for a day with only 1 measurement is also not reported.
The statistical analysis plan, protocol deviations, and interim analyses are not reported in the registry record. It is therefore not possible to determine whether the reported endpoint and analysis population followed a prespecified plan, or whether additional analyses were conducted. These omissions do not establish that such procedures were absent; they mean they cannot be described from the registry information.
Multiplicity and missing data are general interpretive concerns. Multiple outcome tests can increase the chance of a false-positive finding if no suitable strategy is used, while incomplete outcome data can affect both the estimate and its uncertainty depending on why observations are missing and how they are handled. Those are general considerations, not claims about what occurred in this trial.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| ZPL-3893787 | 0 | 65 | 0.0% |
| Placebo | 1 | 33 | 3.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| ZPL-3893787 | 0 of 65 |
| Placebo | 0 of 33 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| ZPL-3893787 | 15 of 65 |
| Placebo | 10 of 33 |
Most frequent serious adverse event terms
| Event term | Organ system | ZPL-3893787 | Placebo |
|---|---|---|---|
| Ulcerative keratitis (ulcus corneae left eye) | Eye disorders | 0 of 65 | 1 of 33 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ZPL-3893787 | Placebo |
|---|---|---|---|
| Headache | Nervous system disorders | 6 of 65 | 4 of 33 |
| Somnolence | Nervous system disorders | 2 of 65 | 1 of 33 |
| Nausea | Gastrointestinal disorders | 2 of 65 | 0 of 33 |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | 0 of 65 | 2 of 33 |
| Pruritus | Skin and subcutaneous tissue disorders | 1 of 65 | 1 of 33 |
| Bradycardia | Cardiac disorders | 1 of 65 | 0 of 33 |
| Sinus arrhythmia | Cardiac disorders | 1 of 65 | 0 of 33 |
| Sinus bradycardia | Cardiac disorders | 1 of 65 | 0 of 33 |
| Dizziness | Nervous system disorders | 1 of 65 | 0 of 33 |
| Pain | General disorders | 1 of 65 | 0 of 33 |
Serious events with the highest arm-level rate: ulcerative keratitis (ulcus corneae left eye) (3.0%).
The registry reports serious adverse event counts and other adverse event counts separately for each arm. For ZPL-3893787, 65 participants were listed at risk for serious adverse events and 0 were listed as affected; 65 were listed at risk for other adverse events and 15 as affected. For placebo, 33 were listed at risk for serious adverse events and 1 was listed as affected; 33 were listed at risk for other adverse events and 10 as affected. The death count was 0 in each arm.
These are counts of participants listed as affected, not an estimate of treatment benefit or a formal comparison of risk. The record does not report the adverse-event observation period or detailed methods for collecting and classifying events. It lists ulcerative keratitis (ulcus corneae left eye) at 3.0% among the top serious terms, but the information reported does not establish which arm that term is associated with. That attribution should not be inferred.
Small numbers of serious events require cautious description. A count of 0 in an arm does not prove that an event cannot occur, and the counts alone do not establish whether an event was caused by the study drug. The registry record does not provide event-level narratives, exposure-adjusted rates, or a statistical comparison of adverse events. The safety counts should therefore be read as descriptive information rather than as evidence of a causal difference between arms.
12. What the Result Does, and Does Not, Mean
The trial record documents a randomized comparison of oral ZPL-3893787 with placebo for adults with moderate to severe atopic dermatitis, with treatment given once daily for 8 weeks. Its primary question concerned change in a participant-reported worst-itch score between baseline and Week 8. The record specifies the scale, assessment schedule, and Full Analysis Set definition. These details clarify what the study was intended to measure.
They do not, on their own, show the size or direction of a treatment effect. The primary outcome values by arm, between-arm estimate, and uncertainty interval are not reported in the registry record. Consequently, it is not possible to say from the posted primary data how much the itch score changed, whether changes differed between arms, or how precise a comparative estimate would be. The same limitation applies to the listed secondary EASI outcome, for which numerical results are not reported in the information described.
The trial’s completed status and enrollment of 98 are study descriptors, not outcome findings. Likewise, the planning assumptions for sample-size illustrations do not establish how likely the completed study was to detect an effect. Sample-size planning is conditional on assumptions and is distinct from the observed estimate and its uncertainty.
The safety counts provide a separate descriptive view. They record participants affected by serious and other adverse events in each arm, as well as deaths. Without event-level information, a stated observation period, or a comparative safety analysis, those counts do not establish causation or a definitive difference between arms.
More broadly, a trial’s result is interpreted through estimates, uncertainty, analysis choices, and the completeness of outcome data, not only its design. Important details about the statistical analysis plan, missing-data handling, multiplicity, and interim analyses are not reported in the registry record. The defensible reading is therefore limited to the documented design and available safety counts; the primary efficacy comparison cannot be quantified from the reported information.
13. Why This Trial Matters Statistically
This study is statistically interesting because its primary question concerns a symptom that participants experience and report repeatedly. The NRS asks about worst itch over the previous 12 hours and is recorded twice daily in an eDiary. Repeated assessments can capture variation over time, while also creating analytic questions about how measurements are combined, how missing entries are handled, and how within-participant dependence is accounted for. The record specifies the assessment schedule and a rule for a day with only 1 measurement, but does not describe the broader analysis of repeated observations.
The trial also illustrates why an endpoint definition is not the same as an endpoint result. The scale has a clear range and interpretation, and the record identifies a baseline-to-Week 8 comparison. Yet without arm-level values, an estimated contrast, and an uncertainty measure, readers cannot judge the magnitude or precision of the primary result. Reporting those elements is central to interpreting a continuous clinical outcome.
There is a further distinction between design planning and completed-trial inference. The record describes sample-size illustrations using a stated significance level, equal allocation, and a normal approximation, with effects expressed as fractions of an observed effect. Such illustrations depend on assumptions and are not observed power. They do not replace transparent reporting of the actual treatment estimate and uncertainty.
Finally, the study has a defined analysis population and lists both primary and secondary outcomes, but the registry information does not report missing-data methods or multiplicity handling. These are not merely technical details: they shape how robustly a reader can interpret estimates and statistical tests. The trial therefore highlights the importance of complete reporting alongside a randomized design. Its registry description identifies the research question and safety counts, while leaving the primary comparative result and several analysis decisions unavailable.
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 most consequential limitation for interpreting this trial from the registry record is that numerical primary outcome results are not reported. Arm-level changes, a between-arm estimate, and its uncertainty are unavailable, so neither the magnitude nor precision of the primary comparison can be evaluated. The secondary EASI outcome is identified, but its numerical result is also not reported in the information described.
The registry describes the primary endpoint as a mean with standard deviation and defines the Full Analysis Set, but does not report how many participants contributed endpoint data or how missing diary observations were handled. It does not explain how twice-daily assessments were summarized for the Week 8 comparison, or identify the model or adjustment strategy used. The rule for a day with only 1 measurement is specified, but that does not answer broader questions about incomplete follow-up.
The record gives a brief design description and lists quadruple masking, while the study summary calls the trial double blind. The roles covered by masking and the practical procedures used are not reported. The allocation ratio and randomization details are also not reported in the registry record. These omissions prevent a more detailed appraisal of conduct and analysis, but do not establish that the procedures were inadequate or absent.
Multiplicity handling, interim analyses, and the statistical analysis plan are not reported. The record’s sample-size description gives general planning assumptions but does not provide the numerical illustrations in the information described. Safety data are counts without a reported observation period or a formal arm comparison. Together, these limits mean the available registry information supports a description of the design, endpoint, and listed safety counts, but not a comprehensive assessment of efficacy, precision, or safety differences.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Determine the Efficacy of ZPL-3893787 in Subjects With Atopic Dermatitis — NCT02424253.
- Registry record last updated 2021-06-10; status last verified 2021-05.
- Results first posted 2021-05-13.
- 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.
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18. Record Summary
NCT02424253 is a completed randomized, placebo-controlled, parallel-group Phase 2 study of oral ZPL-3893787 in adults with moderate to severe atopic dermatitis. The active regimen was 30 mg once daily for 8 weeks; the comparator was placebo once daily. The record reports enrollment of 98 and defines the Full Analysis Set as randomized subjects who received at least 1 dose.
The primary endpoint was change from baseline to Week 8 in the worst-itch NRS, scored from 0 to 10 and assessed twice daily. Change in EASI score was listed as a secondary outcome. Numerical primary and secondary outcome results are not reported in the registry record described. Safety counts list serious and other adverse events by arm and 0 deaths in each arm. The statistical analysis plan, missing-data methods, multiplicity strategy, and interim analyses are not reported in the registry record.