Safety and Pharmacokinetic Study of ATI-50002 in Subjects With Alopecia Universalis (AU) and Alopecia Totalis (AT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Pharmacokinetic Study of ATI-50002 in Subjects With Alopecia Universalis (AU) and Alopecia Totalis (AT) (NCT03315689), a randomized phase 2 study. The primary outcome is Double Blind Period: ATI-50002 Levels in Scalp Biopsy (ng/g) - Pharmacodynamic (PD) Population at Day 2 and Day 29.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, double-blind, parallel-group, vehicle-controlled, multicenter study of ATI-50002 in adults with alopecia universalis or alopecia totalis. The registry lists enrollment as 11. The study’s stated primary objective was to assess safety, tolerability, pharmacokinetics, and pharmacodynamics for ATI-50002 topical solution compared with vehicle.

The official title describes twice-daily topical administration for 28 days, followed by a 12-month long-term open-label extension. The primary endpoint is specified for the double-blind period, with scalp-biopsy measurements at Day 2 and Day 29. The record also lists open-label extension outcomes involving SALT, ALODEX, and subject eyebrow assessment at specified follow-up weeks. These outcomes describe the planned scope of assessment; their numerical results are not reported in the registry record for this account.

Randomization and double masking are stated in the registry. The record does not report the randomization method, allocation concealment procedures, masking assessment, or how participants were assigned to the extension. It identifies vehicle and ATI-50002 interventions, but does not give further operational details about study visits, adherence assessment, or treatment discontinuation.

The adverse-event entries distinguish the vehicle group, the ATI-50002 0.46% topical solution group, and an ATI-50002 0.46% topical solution open-label extension group. Those entries provide group-specific safety counts, but they should not be treated as endpoint efficacy results or as a substitute for the primary pharmacodynamic analysis. The registry record is marked completed; it does not report the numerical primary endpoint estimates or an inferential comparison for them.

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.

Double-blind Period = 28 Days

Reasons for not completing this period:

Open Label Extension = 52 Weeks

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized patients who have a valid assessment at baseline and the subsequent timepoint being reported are included.

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 Double Blind Period: ATI-50002 Levels in Scalp Biopsy (ng/g) - Pharmacodynamic (PD) Population at Day 2 and Day 29, measured over Day 2 - Day 29.

The primary endpoint is ATI-50002 level in scalp biopsy, measured in ng/g at Day 2 and Day 29. It is described as a pharmacodynamic endpoint, with the mean and standard deviation identified as the summary measures. In plain terms, the measure records the amount of ATI-50002 found in sampled scalp tissue at the specified visits.

Measuring a drug concentration in tissue can describe local exposure at the sampled site. This is distinct from measuring a clinical change in hair loss: the endpoint is a concentration, not a SALT, ALODEX, or eyebrow-assessment score. A tissue level can help characterize whether the study detected the compound in scalp samples, but interpretation depends on the actual estimates, their variability, and the analysis population. Those numerical results are not reported in the registry record available for this account.

The registry describes the pharmacodynamic population as randomized patients with a valid baseline assessment and a valid assessment at the subsequent timepoint being reported. It does not give the number contributing to each timepoint or explain how missing or invalid biopsy assessments were handled. It also does not state a clinically meaningful threshold for the scalp concentration, so no conclusion about clinical importance can be drawn from the endpoint definition alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a continuous measurement summarized by a mean and standard deviation. A mean describes the center of observed values, while a standard deviation describes how dispersed individual measurements are around that mean. These summaries are useful for describing tissue concentrations, but they do not by themselves establish a treatment difference. To assess a comparison, readers would also need the arm-specific estimates, the analysis population, and an estimate of uncertainty for the contrast.

What does a confidence interval tell a reader?

In general, a confidence interval expresses the precision of an estimated quantity under the assumptions of the statistical method used. A narrow interval indicates more precision than a wide interval, but its interpretation depends on the analysis and the quantity being estimated. A confidence interval is not a guarantee that the true value lies within its limits. The registry record does not report a confidence interval for the primary endpoint, and it does not state the method that would have been used to calculate one.

How should a comparison of means be understood?

In general, a comparison of means estimates how the average outcome differs between groups. The estimate needs to be considered alongside its uncertainty and the data contributing to it. For a tissue concentration endpoint, the observed values may vary among participants, and the mean can be influenced by the distribution of measurements. The registry record does not report the arm-specific means, standard deviations, treatment contrast, or a model for the primary analysis. It is therefore not possible to reconstruct or interpret a mean contrast from the endpoint description alone.

The record names Day 2 and Day 29 as assessment times. Measurements at different visits can be analyzed separately or incorporated into a model of change over time, but the choice affects the estimand and assumptions. The registry does not report whether the primary comparison was a between-group contrast at each visit, a change from baseline, a comparison of changes, or another approach. No such method should be assumed from the presence of multiple timepoints.

Why do analysis populations matter?

An analysis population determines which participants and measurements contribute to a reported estimate. The endpoint description defines the pharmacodynamic population as randomized patients who have a valid baseline assessment and the subsequent timepoint being reported. This wording indicates that valid assessments are required for inclusion in the relevant reported measure. It does not explain how the registry handled missing biopsies, invalid samples, withdrawn participants, or deviations from assigned treatment. The record also does not report how many participants contributed to each endpoint estimate.

In general, restricting an analysis to participants with valid observed measurements can change the group represented by the estimate if missingness is related to participant characteristics or outcomes. This is one reason a statistical analysis plan typically describes both the target population and the handling of incomplete data. The plan and its missing-data procedures are not reported in the registry record. No imputation method, sensitivity analysis, or rule for invalid samples is stated.

What does randomization contribute?

In general, random assignment is intended to make treatment groups comparable with respect to measured and unmeasured characteristics, on average, before treatment. This supports causal interpretation when allocation, follow-up, and analysis preserve the randomized comparison. The record states that the study was randomized and double-blind, but it does not report the allocation procedure, concealment method, adherence, or detailed analysis approach. The design labels alone do not reveal whether all randomized participants were included in a particular analysis.

Double masking can reduce the risk that knowledge of treatment assignment influences participant reports, clinical assessments, or study conduct. That protection is not automatic: it depends on how masking was maintained and whether it was compromised. The registry record does not report masking procedures or an assessment of whether treatment assignment could be guessed. These details should not be inferred.

How should planning illustrations be read?

In general, a sample-size calculation describes how many participants may be needed under specified assumptions to detect a chosen effect with a chosen error rate and power. The record’s planning assumptions specify a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of the observed effect. They also state that time-to-event calculations use total events, while other calculations use participants per arm. These are planning assumptions, not observed trial outcomes, and a planning illustration is not observed power.

The registry record does not report a sample-size justification for the trial’s original design. It also does not report a protocol-level statistical analysis plan or interim analysis methods. No claim about the planned power, stopping rules, or pre-specified analysis can be made from the information. A sample-size illustration based on an observed effect, where one is used, is not evidence that the original study was designed around that effect.

Finally, the record lists 22 outcome measures and 0 analyses. The number of listed outcomes does not establish which endpoint comparisons were formally tested, whether tests were adjusted, or how outcome reporting was selected. Statistical methods are needed to connect outcomes to estimates and uncertainty; endpoint labels and design descriptions alone cannot supply that missing evidence.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures, including the primary scalp-biopsy endpoint and secondary outcomes covering SALT, ALODEX, and subject eyebrow assessment during the open-label extension. It lists 0 analyses. The presence of multiple outcomes raises a general multiplicity question: when several hypotheses are tested, the chance of at least one apparently unusual result can increase if no adjustment or hierarchy is used. The registry record does not report a multiplicity strategy, a testing hierarchy, or which outcomes were intended to support confirmatory claims.

The primary endpoint is described at Day 2 and Day 29, but the record does not explain whether both visits were separate primary comparisons or how they were combined. The handling of multiple timepoints is therefore not reported in the registry record. It would be inappropriate to infer an adjustment method or a prespecified decision rule.

The endpoint population requires a valid baseline and subsequent timepoint assessment. The record does not report how many assessments were missing or invalid, whether missingness differed by group, or how incomplete data were handled. It does not state whether analyses used imputation, complete cases, or another method, and no sensitivity analysis is described. The wording defining the population should not be read as a full missing-data plan.

Likewise, the registry record does not report a detailed analysis population for each outcome, a protocol-level statistical analysis plan, or a method for handling deviations from assigned treatment. These omissions limit assessment of whether the results, if reported elsewhere, would align with a prespecified analysis. The endpoint and population descriptions are not enough to fill those gaps.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: depression (10.0%).

The registry reports adverse events separately for the vehicle topical solution group, the ATI-50002 0.46% topical solution group, and the ATI-50002 0.46% topical solution open-label extension group. For the vehicle group, 0 participants are listed as having a serious adverse event, and 1 as having another adverse event, among 4 at risk. For the ATI-50002 group, the corresponding figures are 0 and 1 among 7 at risk. For the open-label extension group, they are 1 and 7 among 10 at risk. Deaths are listed as 0 for each group.

The registry also lists depression as a serious adverse-event term at 10.0%. The record does not give further context for that term in the information, so its denominator and relationship to the group-level entries should not be inferred.

These are descriptive counts. They do not, by themselves, show that an event was caused by treatment or establish a comparative safety effect. The open-label extension is not the same comparison as the blinded vehicle-controlled period. The record does not provide event timing, duration, severity detail beyond serious classification, or adjudication procedures. The figures should therefore be read as reported safety counts rather than as a complete account of safety evidence.

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

The study record establishes that investigators conducted a randomized, double-blind, vehicle-controlled Phase 2 study of ATI-50002 topical solution in adults with alopecia universalis or alopecia totalis. It identifies the primary endpoint as ATI-50002 concentration in scalp biopsy at Day 2 and Day 29, summarized as a mean and standard deviation. It also records safety counts for the vehicle, active-treatment, and open-label extension groups.

Those design and endpoint details do not show the primary endpoint result. The numerical scalp-biopsy estimates are not reported in the registry record available for this account. Without the estimates and their uncertainty, the direction and magnitude of any observed difference cannot be described, and no conclusion about statistical significance or precision is possible. No clinical outcome effect can be inferred from the endpoint definition alone.

The safety counts are also limited in what they establish. They describe numbers of participants with reported events in the listed groups, but do not prove causation. The open-label extension counts come from a distinct study period and should not be treated as a randomized comparison with vehicle. Zero deaths in the listed groups is a registry count, not a guarantee that a treatment has no risk.

In general, a small study can provide descriptive information while leaving estimates imprecise, but the registry record does not provide the endpoint results needed to assess precision in this study. Enrollment is listed as 11; that figure does not identify the number with valid data at each visit. The record does not report endpoint-specific denominators or a full missing-data analysis.

Accordingly, the record supports a careful account of the trial’s design, intended measurements, and posted adverse-event counts. It does not support claims about the size or clinical relevance of a pharmacodynamic effect, the efficacy of treatment, or a definitive comparative safety conclusion.

13. Why This Trial Matters Statistically

This study is statistically notable because its primary endpoint is a tissue concentration rather than a clinical score. The endpoint asks whether ATI-50002 levels were measured in scalp biopsies at specified visits. That distinction matters: drug concentration and clinical change are different quantities, and one cannot be substituted for the other without an analysis linking them.

The randomized, double-blind, vehicle-controlled design provides a framework for comparing active treatment with vehicle during the blinded period. In general, randomization can help balance baseline characteristics, while masking can limit some forms of assessment and behavior bias. The registry record does not report enough procedural detail to judge how well those protections were implemented, and it does not provide the primary endpoint estimates needed to evaluate the comparison.

The study also includes an open-label extension and several listed outcomes. This creates interpretive distinctions between the blinded comparison and later extension assessments. Outcomes, follow-up periods, and analysis populations should not be treated as interchangeable. The registry record does not report a multiplicity strategy or detailed analysis plan, so the status of the listed outcomes as confirmatory or exploratory is not reported.

For biostatisticians and clinical researchers, the record illustrates why endpoint definitions and numerical results must be read together. A clear measurement description supports understanding what was intended to be observed. But without arm-specific values, uncertainty estimates, and an account of missing data, the record cannot establish how much evidence the measurement provides. The distinction between a planned objective, an observed estimate, and a statistical conclusion is central to responsible interpretation.

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 direct limitation is that the registry record does not report numerical results for the primary endpoint. Although the measurement, unit, summary statistics, and visit schedule are specified, the actual mean and standard deviation values are absent in the registry record. No treatment contrast, confidence interval, or p-value is reported, limiting assessment of effect size and precision.

The endpoint population is defined using valid baseline and subsequent assessments, but endpoint-specific participant counts are not reported. The record does not state how missing or invalid biopsy measurements were handled, whether participants were excluded after randomization, or whether sensitivity analyses were conducted. These details matter when interpreting a complete-case or otherwise restricted estimate.

The study is listed with enrollment of 11, while the safety record gives group-specific numbers at risk for the blinded and extension groups. These figures do not establish how many participants contributed to the primary endpoint at each visit. The record does not report reasons for discontinuation or the flow of participants through the study.

Important design and analysis details are also not reported in the registry record, including the randomization method, allocation concealment, full statistical analysis plan, multiplicity approach, and any interim analysis procedures. The record does not provide a sample-size justification for the original design. A planning illustration based on an observed effect, where applicable, should not be treated as the trial’s original design rationale or as observed power.

Finally, adverse-event counts are descriptive and lack detail on event timing, duration, adjudication, and attribution. The open-label extension figures do not represent the same comparison as the blinded vehicle-controlled period. These limitations leave substantial uncertainty about both endpoint interpretation and the completeness of the safety account.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Pharmacokinetic Study of ATI-50002 in Subjects With Alopecia Universalis (AU) and Alopecia Totalis (AT) — NCT03315689.
• Registry record last updated 2020-07-02; status last verified 2020-06.
• Results first posted 2020-07-02.
• 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

NCT03315689 is a completed Phase 2, randomized, double-blind, parallel-group, vehicle-controlled multicenter study of ATI-50002 topical solution in adults with alopecia universalis or alopecia totalis. The official title describes twice-daily treatment for 28 days and a 12-month open-label extension. Enrollment is listed as 11.

The primary endpoint is ATI-50002 level in scalp biopsy, in ng/g, at Day 2 and Day 29, summarized by mean and standard deviation. The registry record does not report numerical results for this endpoint. It lists 22 outcome measures and 0 analyses.

Safety entries report serious and other adverse-event counts for vehicle, ATI-50002, and the open-label extension groups; deaths are listed as 0 in each group. These counts are descriptive and do not establish causation or a comparative treatment effect. The registry record does not report a detailed statistical analysis plan, multiplicity procedure, or missing-data method.