Adrenal Suppression and Pharmacokinetics of Topicort® Spray, 0.25% in Pediatric Patients With Plaque Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adrenal Suppression and Pharmacokinetics of Topicort® Spray, 0.25% in Pediatric Patients With Plaque Psoriasis (NCT02340169), a na phase 4 study. The primary outcome is The Number of Participants With Hypothalmic Pituitary Adrenal Axis Function Suppression as Measured by Cortisol Response Test.

2. Clinical Question

The study’s stated objective was to evaluate the potential for Topicort® Topical Spray, 0.25%, to suppress hypothalamic pituitary adrenal axis function. Its secondary objectives were to evaluate efficacy parameters, pharmacokinetics, and the adverse-event profile. The registry lists adverse event and Cpre-ss among the secondary outcomes.

This is a safety study with a single treatment group, not a randomized comparison. The primary question is therefore descriptive: the endpoint is a count of participants meeting specified cortisol-response criteria during the study. The registry record does not report a comparator-based estimate of treatment effect, nor does it report the number of participants meeting the primary endpoint. It also does not report the age range, baseline cortisol-response status, or other participant characteristics needed to describe the study population in greater detail.

The central statistical issue is the distinction between observing an endpoint within a treated group and estimating a difference attributable to treatment. A single-group count can describe what was recorded under the study conditions, but without a control group it cannot, by itself, establish how that count would differ under another treatment or without treatment.

3. Trial Design

The registry classifies this study as phase 4 and completed. Its listed enrollment is 129. The study is open label, with masking listed as none, and uses a single-group model. Allocation is listed as not applicable. The intervention was Topicort® (desoximetasone) Topical Spray, 0.25%, twice a day for 28 days. The official title describes maximal-use treatment and identifies the study as an open-label safety study evaluating adrenal suppression and pharmacokinetics in pediatric patients with plaque psoriasis.

The registry record lists a start date of 2015-01-23 and a primary completion date of 2019-11-22. These dates describe the registered study timeline; they do not supply individual participant follow-up information. The registry status is completed. The record does not report how many participants completed treatment, how many discontinued, or how long participants were followed after the treatment period.

Because this is a single-group study, it does not have a randomized treatment allocation or a like-for-like control arm. The observations can describe the participants receiving the listed intervention, but they do not create a concurrent estimate of what would have happened to comparable participants under a different condition. The open-label design also means masking is not part of the registered design.

The registry describes the main objective as assessment of potential hypothalamic pituitary adrenal axis suppression. Secondary objectives include efficacy parameters, pharmacokinetics, and adverse events. It lists three outcome measures and one analysis, but the statistical methods used for the analysis are not reported in the registry record. A sample-size justification, details of any interim analyses, and a fuller analysis plan are also not reported in the registry record. The planning assumptions associated with illustrations are not evidence of the trial’s original design rationale.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Prior to the Protocol Amendment if a subject was found to have an abnormal adrenal function test after the baseline Cortisol Response test the subject was notified to discontinue the drug and follow up with the Investigator. After the protocol amendment a screening visit was added so that subjects with abnormal tests would not be randomized to study drug.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as The Number of Participants With Hypothalmic Pituitary Adrenal Axis Function Suppression as Measured by Cortisol Response Test, measured over 28 days.

The primary endpoint is the number of participants with hypothalamic pituitary adrenal axis function suppression as measured by a cortisol response test. The assessment timeframe is 28 days. A participant is considered to have potential suppression if at least one of the registry’s stated criteria is met: the 30-minute post-injection cortisol level is not at least 7 mcg/100 ml greater than the basal level, or the post-stimulation level is at most 18 mcg/100 ml.

This endpoint turns a laboratory response into a participant-level binary classification: each participant either meets at least one criterion or does not, according to the stated definition. The reported measure is a count of participants, rather than a continuous summary of cortisol values. The registry record does not report the number meeting either criterion, the number meeting both, or the total primary-endpoint result.

In general, a stimulated response test is used to assess how a physiological system responds to a challenge; in this study, the specified cortisol response is the operational measure of potential axis suppression. The threshold-based definition makes the endpoint interpretable as a count, but it also means that the result depends on the stated cutoffs and test procedure. The record does not report further details about measurement timing, laboratory methods, or how borderline or missing test results were handled.

The primary endpoint is relevant to the study’s stated safety objective, but a count alone would not describe the size or persistence of any change in cortisol response. Nor would it establish a causal contrast with another treatment in the absence of a comparator group. Those limitations matter particularly because the endpoint result itself is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary outcome is a count of participants classified as meeting at least one cortisol-response criterion. That makes it a binary participant-level outcome, even though the overall result is expressed as a count. The registry specifies the criteria and timeframe, but it does not report the analysis method used to calculate or present the endpoint result. The primary endpoint count itself is not reported in the registry record.

What does a participant count mean?

In general, a count records how many observations fall into a defined category. For a participant-level binary endpoint, the category is whether the person meets the endpoint definition. A count is descriptive; by itself it does not provide a measure of uncertainty, a comparison with another group, or evidence that treatment caused the outcome. To interpret a count fully, readers also need the denominator, the endpoint definition, the handling of missing assessments, and any interval or inferential analysis. The registry specifies the endpoint definition and lists enrollment, but it does not report the primary count, its denominator at assessment, or the analysis details.

Why does the cortisol threshold matter?

The primary endpoint definition uses two criteria, with either one sufficient for classification. One criterion concerns the relationship between the 30-minute post-injection cortisol level and the basal level; the other concerns the post-stimulation level. In general, threshold-based rules make a result easier to categorize, but classification can depend on measurement procedures and on values near a cutoff. The registry record does not report laboratory procedures, repeat testing rules, or the handling of borderline results. It also does not state how results were treated if one part of the test was missing.

What can a single-group analysis establish?

In general, a single-group study can describe observations within the group that received the intervention. A comparative treatment effect requires a comparison against a suitable alternative condition. This study is listed as single group, with allocation not applicable and no masking. The record therefore does not support a randomized between-group treatment comparison. Even if an endpoint count were available, it would describe the registered group rather than isolate a causal effect relative to a control.

General principles of statistical inference distinguish a point estimate from its precision. A confidence interval describes a range of values compatible with the observed data under the method used; it does not guarantee that the true value lies in that range. A p-value, when reported, addresses compatibility with a specified statistical model and null hypothesis; it does not measure clinical importance. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. No specific inferential procedure can be attributed to the trial from the available record.

What is not known about the analysis?

The registry lists one analysis, but the analysis method, analysis population, and missing-data approach are not reported in the registry record. The record does not say whether all enrolled participants were included in the primary analysis, how participants with incomplete cortisol testing were treated, or whether any sensitivity analyses were conducted. It also does not report adjustment for baseline characteristics or other covariates. These omissions limit assessment of how the posted endpoint, if available, would have been derived.

The record lists three outcome measures and identifies secondary objectives involving efficacy parameters, pharmacokinetics, and adverse events. The statistical approach to these outcomes and any plan for handling multiple outcomes are not reported in the registry record. In general, evaluating many outcomes can increase the chance of at least one apparently notable finding if each is tested separately; prespecified methods can address that issue. The record does not state whether multiplicity adjustments were planned or used.

How should planning illustrations be read?

General sample-size calculations describe the number of participants that might be needed under stated assumptions. The planning assumptions described for illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of an observed effect. Such calculations are planning illustrations, not observed power and not proof that the original trial was designed around those assumptions. The registry record does not report the trial’s own sample-size justification. Because this study is a single-group design, assumptions involving equal allocation between two arms do not describe its registered treatment structure.

In general, power is a design quantity based on a prespecified effect, variability, significance level, and analysis. It is not a measure of the probability that a result is true after the study is complete. No observed primary effect is reported in the registry record, and no trial-specific power calculation or analysis assumptions are reported. Therefore, the planning framework should not be treated as evidence about the study’s statistical power or as a substitute for its missing primary endpoint result.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort 1", "Cohort 2", "Cohort 3")
n      <- c(60, 30, 10)
events <- c(21, 13, 2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort 1  60  21  35.0  23.1  48.4  24.2  47.6  24.2  47.7
ARM  Cohort 2  30  13  43.3  25.5  62.6  27.4  60.8  27.3  60.9
ARM  Cohort 3  10  2  20.0  2.5  55.6  5.7  51.0  6.0  51.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, with adverse event and Cpre-ss identified among the secondary outcomes. The primary endpoint concerns participants meeting the cortisol-response criteria. However, a plan for controlling the chance of false-positive findings across multiple outcomes is not reported in the registry record. The record does not say whether secondary outcomes were tested inferentially, whether any hierarchy of outcomes was prespecified, or whether multiplicity adjustments were made. Without that information, the secondary outcomes cannot be interpreted as a defined family of confirmatory tests.

The missing-data approach and analysis populations are also not reported in the registry record. Although enrollment is 129 and the adverse-event listings show 129 at risk in each listed category, the record does not describe participant flow, treatment completion, missing cortisol assessments, or the population used for the primary endpoint analysis. The fact that an adverse-event denominator is listed does not establish that all participants had an evaluable primary endpoint.

In general, missing outcome data can affect both the estimated event count and the interpretation of a study, particularly if missingness is related to participant characteristics or outcomes. Methods such as excluding participants with missing assessments or using an imputation procedure make different assumptions. No method can be attributed to this study because the handling of missing data is not reported in the registry record. The record likewise does not identify an intention-to-treat, per-protocol, or safety analysis population.

These gaps prevent readers from determining how complete the primary endpoint data were, whether the reported safety counts use the same participant set, and how many statistical comparisons informed any conclusions. The registry record does not report interim analyses or a detailed statistical analysis plan.

12. 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.

The adverse-event listing reports 129 participants at risk for serious adverse events, with 0 affected, and 129 at risk for other adverse events, also with 0 affected. Deaths are listed as 0. No serious adverse-event terms are listed. These entries describe the recorded counts in the registry; they do not provide event narratives, severity details beyond the serious category, or information about timing and duration.

In general, an observed count of zero is not equivalent to evidence that the underlying risk is zero. The precision of a safety estimate depends on the amount and completeness of follow-up and on the analysis used. No confidence intervals or further methods for these counts are reported in the registry record. The record also does not describe how adverse events were collected, how long participants were monitored for these events, or how the categories were defined beyond their labels.

The listed denominator is 129 in each category, while enrollment is also 129. The registry does not report participant flow or explain whether all participants contributed the same duration of safety observation. These figures should therefore be read as posted counts, not as a complete account of all possible adverse events or as a comparison with another treatment.

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

The record establishes the study’s registered focus: potential hypothalamic pituitary adrenal axis suppression during treatment with Topicort® (desoximetasone) Topical Spray, 0.25%, in pediatric patients with plaque psoriasis. It describes a 28-day treatment schedule and defines the primary endpoint using cortisol-response criteria. It also reports adverse-event counts for the listed categories. These details explain what the study was designed to examine and how its primary endpoint was defined.

However, the primary endpoint result is not reported in the registry record. The number of participants who met the suppression criteria, the denominator with an evaluable cortisol test, and any estimate of precision are not reported. The record therefore does not allow readers to quantify the frequency of the primary outcome from the registered information. It also does not report outcome results for the stated efficacy and pharmacokinetic objectives.

The reported adverse-event entries show 0 affected for the serious category and 0 affected for other adverse events, among 129 listed at risk in each category, with 0 deaths. These are descriptive registry counts. They do not establish that no adverse events could occur, and they do not compare risk with another treatment or an untreated group. The record does not provide interval estimates or enough follow-up detail to assess the precision of the counts.

More generally, a single-group, open-label study can describe outcomes in the treated group but cannot, without a comparator, estimate a randomized treatment difference. The absence of masking and the unreported analysis details further constrain evaluation of outcome ascertainment and statistical uncertainty. The study’s completed status does not fill the gap left by unreported primary results.

The responsible interpretation is therefore limited: the registry documents a phase 4, open-label, single-group safety study, its intervention and endpoint definition, and the posted adverse-event counts. It does not report enough primary outcome or analysis information to judge the observed frequency of cortisol-response suppression or to make a comparative treatment-effect claim.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its stated primary objective and its registered design need to be read together. The primary measure is a count of participants meeting a laboratory-based criterion, while the study is single group and open label. A count can describe the treated group, but it cannot by itself answer a comparative question about what would have happened under another treatment or without treatment. The design therefore defines the scope of conclusions before any result is considered.

The registry also illustrates why endpoint definitions and reported results are both necessary. It gives a precise rule for classifying potential suppression, including the post-injection and post-stimulation criteria, but does not report how many participants met that rule. A detailed endpoint definition cannot substitute for the missing result, denominator at assessment, or uncertainty estimate. Readers need those elements to understand the observed data and their precision.

The safety entries provide another useful distinction. A posted zero count is a report about observed events in a stated denominator, not proof that an event cannot occur. In general, event counts are more informative when the record also describes ascertainment, follow-up, missingness, and interval estimates. Those details are not reported in the registry record, so the counts should be read narrowly.

Finally, the registry’s listing of secondary objectives and multiple outcomes raises a general statistical issue: conclusions depend on prespecified analysis choices, missing-data rules, and how multiple outcomes are handled. The analysis plan is not reported in the registry record. For clinical researchers, the key lesson is to distinguish the study’s objective, the operational endpoint definition, the actual posted results, and the limits imposed by design and reporting. In this record, the first two are described more fully than the primary result and its statistical analysis.

15. 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 the primary endpoint count, despite specifying how potential suppression was defined. Without that result, readers cannot assess the observed frequency of participants meeting the endpoint or its precision. The number with evaluable cortisol testing and the treatment of missing tests are also not reported.

The study has a single-group, open-label design, with no masking and no separate comparator. This prevents a concurrent randomized comparison and limits causal interpretation. The record does not report participant characteristics beyond the pediatric plaque psoriasis population, an age range, baseline cortisol-response status, or participant flow. It also does not describe adherence, treatment discontinuation, or follow-up beyond the 28-day endpoint timeframe.

Although the registry identifies secondary objectives and outcomes, results for efficacy parameters and pharmacokinetics are not reported in the record described. Statistical methods, confidence intervals, p-values, multiplicity procedures, interim analyses, analysis populations, and missing-data methods are not reported in the registry record. A trial-specific sample-size justification is not reported either. These omissions make it difficult to evaluate the precision, completeness, and analysis choices behind the registered outcomes.

For safety, the record reports zero affected participants in the listed categories and zero deaths, but does not provide event terms, event timing, monitoring duration, or interval estimates. The listed denominator alone does not resolve whether every participant had equivalent follow-up. The registry record supports a description of the study structure and the posted counts, but not a complete assessment of primary outcomes, comparative effects, or statistical uncertainty.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Adrenal Suppression and Pharmacokinetics of Topicort® Spray, 0.25% in Pediatric Patients With Plaque Psoriasis — NCT02340169.
• Registry record last updated 2023-03-28; status last verified 2023-02.
• Results first posted 2023-03-28.
• 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.

19. Record Summary

This completed phase 4 study enrolled 129 pediatric patients with plaque psoriasis and evaluated Topicort® (desoximetasone) Topical Spray, 0.25%, twice a day for 28 days. It was open label, used a single-group design, had no masking, and listed allocation as not applicable. The study’s primary objective concerned potential hypothalamic pituitary adrenal axis suppression, measured by a cortisol response test. The registry defined potential suppression using either of two specified cortisol-response criteria at the 28-day timeframe.

The record lists secondary objectives involving efficacy parameters, pharmacokinetics, and adverse events. It reports 0 serious adverse events among 129 at risk, 0 other adverse events among 129 at risk, and 0 deaths. The primary endpoint result and a detailed statistical analysis plan are not reported in the registry record. Consequently, the record describes the study design, endpoint definition, and posted safety counts, but does not provide the primary outcome frequency or its statistical precision.