DFD06 Cream vs Clobetasol Propionate Cream, 0.05% Hypothalamic- Pituitary-Adrenal (HPA) Axis Suppression Study in Patients With Moderate to Severe Plaque Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for DFD06 Cream vs Clobetasol Propionate Cream, 0.05% Hypothalamic- Pituitary-Adrenal (HPA) Axis Suppression Study in Patients With Moderate to Severe Plaque Psoriasis (NCT02131324), a randomized phase 2 study. The primary outcome is The Percentage of Subjects With HPA Axis Suppression..

2. Clinical Question

3. Trial Design

The registry describes NCT02131324 as a randomized, open-label, parallel-group Phase 2 study in participants with moderate to severe plaque psoriasis. It lists Promius Pharma, LLC as the sponsor and an enrollment of 50. The recorded study start is 2014-05-08, and primary completion is listed as 2016-04; the status is completed. The registry record does not report further detail on how randomization was generated or how allocation was concealed.

Participants were assigned to DFD06 Cream or clobetasol propionate cream, 0.05%. Both products were applied twice a day for 15 days. Masking was listed as none, so the study was open-label. The parallel design means the comparison is between groups assigned to different products, rather than a crossover comparison in which participants receive both products in sequence.

The stated purpose was to evaluate the potential for HPA axis suppression and systemic drug absorption with DFD06 Cream compared with clobetasol propionate cream, 0.05%. The posted primary outcome is the percentage of participants with HPA axis suppression at Day 15, measured by serum cortisol levels after a cosyntropin (ACTH) test. The registry lists one outcome measure and one analysis. It does not report a posted secondary outcome result.

The primary analysis population was the safety population. It included participants who received at least one confirmed dose of study product and had any post-baseline safety information. The reported arm counts for the primary endpoint are 22 for clobetasol propionate cream, 0.05%, and 24 for DFD06 Cream. The registry record does not explain the difference between the overall enrollment and the arm counts in this endpoint analysis, so no further account of that difference can be inferred from the posted information.

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: Washout was needed at Screening Visit if prohibited therapies were in use. The screening adrenocorticotropic hormone (ACTH) stimulation test was conducted at least 14 days and no more than 28 days prior to the Baseline Visit.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All summaries and analyses were performed on the safety population. All subjects who received at least one confirmed dose of study product and provided any post-baseline safety information were included in the safety population. No imputation was made for missing safety data.

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 Percentage of Subjects With HPA Axis Suppression., measured over Day 15.

The primary endpoint is the percentage of participants with HPA axis suppression at Day 15. Suppression was assessed using serum cortisol levels after a cosyntropin (ACTH) test. The endpoint is binary at the participant level: each person is classified according to whether the test result meets the study’s definition of suppression, and the group result is expressed as a percentage.

In general, the HPA axis is part of the body’s hormonal response system, and a cortisol response after cosyntropin testing can be used to assess adrenal response. A suppression endpoint therefore addresses a potential systemic safety effect of topical treatment, rather than the skin disease response itself. The registry record does not provide the cortisol threshold or other operational details used to classify suppression, so those criteria cannot be described further.

The posted timeframe is Day 15, following the recorded twice-daily application schedule. This makes the result a measurement at the specified study time point; it does not describe longer-term outcomes. The endpoint population was the safety population, defined as participants with at least one confirmed dose and post-baseline safety information. The record says that missing safety data were not imputed. As a result, the reported percentages reflect the available safety information under that population definition, not an imputed estimate for participants with missing safety measurements.

7. Results Posted in the Registry

• DFD06 Cream: 12.5% (3/24) versus 36.4% (8/22) on control; risk difference -23.9 percentage points (95% CI -47.9 to 0.2), risk ratio 0.34 (0.10–1.13); unadjusted two-proportion z-test p = 0.058.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a binary outcome summarized as a percentage: whether each participant met the study definition of HPA axis suppression at Day 15. For a binary outcome, a group percentage is calculated from the number of participants with the event and the number included in that group’s analysis. The posted counts are 8 of 22 for clobetasol propionate cream, 0.05%, and 3 of 24 for DFD06 Cream. No imputation was made for missing safety data, and the analysis population was the safety population described in the registry.

What does a risk difference describe?

In general, a risk difference subtracts one group’s event proportion from the other group’s event proportion, with the direction determined by which group is placed first. The unadjusted re-calculation reports the DFD06 Cream comparison as -0.239. The negative sign indicates a lower observed event proportion in the DFD06 Cream group under that comparison order. This is an absolute difference on the proportion scale, not a relative measure. It should not be confused with a percentage-point value because the posted estimate is expressed as a proportion.

The re-calculation also reports a risk ratio of 0.344, with limits 0.104 and 1.135, and an odds ratio of 0.25, with limits 0.056 and 1.108. In general, a risk ratio compares event proportions, while an odds ratio compares event odds. Both are relative measures, and their numerical interpretation differs from the risk difference. The posted intervals for these relative measures include the value representing no relative difference. Estimates and interval limits are not substitutes for the registry’s own analysis, which is reported separately.

What does the p-value tell the reader?

In general, a p-value describes how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions were correct. It is not the probability that the null model is true, and it does not measure the size or clinical importance of an effect. The unadjusted recalculation reports p = 0.058. The registry reports p = 0.086 for its ANOVA equivalence analysis. Because these values come from different analyses, they answer questions under different methods and cannot be read as if they were two versions of a single identical test.

The registry’s use of the term equivalence deserves care. In general, an equivalence analysis asks whether a difference is sufficiently small to lie within prespecified bounds. The existence of a p-value labelled equivalence does not reveal the bounds or the exact decision rule. Those details, as well as the estimate and interval from the sponsor analysis, are not reported in the registry record. A reader should therefore report the analysis as the registry labels it, without inferring an equivalence margin or making an equivalence claim from the p-value alone.

Why report an interval as well as a point estimate?

In general, a point estimate gives one value for the observed comparison, while an interval communicates uncertainty around that estimate under the method used. The risk-difference interval is -0.479 to 0.002. Its width reflects the imprecision in this comparison; the interval crosses from negative to positive values. The estimate alone is therefore not enough to characterize the result. The interval indicates that the direction and magnitude of the population difference remain uncertain under this unadjusted calculation.

The registry record does not state the confidence level or construction method for the re-calculated interval. It should therefore be described as the posted interval rather than assigned a confidence level or a method not documented there. General properties of intervals can aid interpretation, but they do not fill in missing technical details.

What does over-dispersion mean for this endpoint?

For a binary outcome, over-dispersion is not the central issue in the same way it can be for count outcomes whose variability exceeds a model’s assumptions. Here, the primary result is a participant-level event proportion. General concerns instead include the limited amount of information in the observed group counts, uncertainty in the event proportions, and whether the chosen analysis matches the study question. No additional model for over-dispersion is reported in the registry record, and the posted results do not permit an assessment of unreported model diagnostics.

The trial’s sponsor analysis is identified as ANOVA, but the registry does not report its model specification, covariates, transformations, or assumptions. The re-calculation is explicitly unadjusted and uses posted summary statistics. It does not reconstruct any adjustment or other feature of the sponsor’s analysis. This distinction matters because different methods may target different estimands or use different assumptions even when applied to the same endpoint.

Finally, statistical analysis depends on the defined population and handling of missing observations. The safety population included participants who had a confirmed dose and post-baseline safety information, and missing safety data were not imputed. The registry does not report the number or pattern of missing Day 15 cortisol assessments, or whether every participant in the safety population contributed to the endpoint calculation. Those details limit further evaluation of the analysis population and missingness.

10. Confidence Intervals and Precision

The risk-difference estimate from the unadjusted re-calculation is -0.239, and its interval runs from -0.479 to 0.002. The interval is broad relative to the point estimate and crosses from negative to positive values. In practical statistical terms, the observed comparison does not pin down a single direction or a narrowly defined magnitude of difference. The point estimate describes the center of this calculation, but the interval is important for understanding how uncertain that estimate is.

For the risk ratio, the reported estimate is 0.344, with limits 0.104 and 1.135. For the odds ratio, the estimate is 0.25, with limits 0.056 and 1.108. These relative-effect intervals also extend across their respective no-difference values. The measures use different scales, so their numerical values should not be compared as if they represented the same quantity. The event percentages and counts provide a direct descriptive account, while the relative estimates and risk difference express the comparison in distinct ways.

In general, an interval’s width reflects precision under the chosen method: narrower intervals indicate more precise estimates, while wider intervals leave more uncertainty about the underlying value. Precision depends in part on the information available, including the number of observed events and participants, and on the analysis method. The group counts for this endpoint are 22 and 24, with 8 and 3 observed events. The interval limits should be interpreted as statistical uncertainty, not as a range containing every individual participant’s outcome.

The confidence level and interval-construction method are not reported in the registry record for the re-calculation. The sponsor analysis also has no posted effect estimate or interval. Accordingly, the interval discussion applies to the unadjusted re-calculation and should not be attributed to the sponsor’s ANOVA equivalence analysis.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are expressed as participants per arm, not as total events. They are illustrations based on the observed effect, rather than a report of the original trial’s design calculation. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect used for each illustration is the stated fraction of the observed effect.

For planning for 100% of the observed effect, the figures are 50 participants per arm for 80% power and 67 participants per arm for 90% power. For planning for 75% of the observed effect, they are 97 participants per arm for 80% power and 129 participants per arm for 90% power. For planning for 50% of the observed effect, they are 233 participants per arm for 80% power and 311 participants per arm for 90% power.

In general, power is the probability that a planned study will detect an effect of a specified size under the assumptions used in the calculation. The 80% and 90% columns describe alternative planning targets: the 90% target seeks a greater chance of detecting the specified effect, and therefore calls for more participants per arm in these illustrations. The rows also demonstrate the general pattern that smaller effects require more participants to detect, all else being equal.

These figures are not observed power. They do not describe the probability that the completed study detected an effect, and they are not evidence about the trial’s original sample-size justification. The original design assumptions and sample-size justification are not reported in the registry record. A planning curve should be read in the same illustrative way: it relates assumptions about effect size and study size, rather than documenting what the completed trial was powered to detect.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.364; treatment proportion p₁ = 0.125; average p̄ = 0.244.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6077 = 1.1910.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5838 = 0.4913.
4. n = (1.1910 + 0.4913)² / (-0.2386)² = 49.7, rounded up to 50 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.363636363636364                          # control proportion
p1 <- 0.125                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2131324)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 50 (80% power), 67 (90% power)
 75% of observed effect: n per arm = 97 (80% power), 129 (90% power)
 50% of observed effect: n per arm = 233 (80% power), 311 (90% power)
power.prop.test: 49.7 
Simulated power at n = 50 per arm: 0.816 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The registry reports the sponsor’s analysis as an ANOVA equivalence analysis, with p = 0.086. It does not provide the sponsor analysis’s effect estimate, interval, equivalence margin, or further specification of the method. The result can therefore be described as a reported equivalence analysis with that p-value, but the details needed to interpret the equivalence criterion are not available in the registry record.

The separate unadjusted re-calculation uses the posted event counts and group sizes to estimate a risk difference of -0.239, with interval limits of -0.479 and 0.002, and reports p = 0.058. This is not a reconstruction of the sponsor’s ANOVA. The recalculation and sponsor result differ in method and stated analysis purpose, so their p-values should not be compared as though they were outputs from the same test.

The registry record does not flag a discrepancy between its reported analysis and the re-calculation. The re-calculation remains a supplementary, unadjusted estimate based on the posted summaries; it does not replace the sponsor’s analysis or recover information absent from the record. Neither p-value, on its own, establishes equivalence or the absence of a meaningful difference. The sponsor’s label and reported result should be retained, while noting that the necessary equivalence details are unavailable.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and one analysis, and it posts no secondary outcome results. This does not establish whether the original protocol included other planned outcomes or analyses, or whether any multiplicity strategy was specified. Multiplicity refers, in general, to the increased chance of a false-positive finding when several hypotheses are tested. A prespecified plan can address that issue, but the statistical plan and any multiplicity adjustment are not reported in the registry record. No conclusion about multiplicity control can therefore be made.

The registry identifies the primary analysis population as the safety population. It includes participants who received at least one confirmed dose and provided any post-baseline safety information. The record states that no imputation was made for missing safety data. This is relevant because analyses without imputation use observed information rather than filling in missing values through a statistical procedure. The record does not report the number or pattern of missing endpoint measurements, or the assumptions used in handling them beyond the statement that no safety-data imputation was made.

It is also not reported whether the endpoint analysis included every member of the safety population or whether any additional endpoint-specific criteria applied. The arm summaries give 22 participants for clobetasol propionate cream, 0.05%, and 24 for DFD06 Cream, while the registry’s enrollment is 50. The record does not explain this difference; it should not be resolved by assuming reasons for exclusion or missingness.

The registry does not report an intention-to-treat analysis, a per-protocol population, interim analyses, a stopping rule, or sensitivity analyses for missing data. These items are not established simply by the randomized design or by the endpoint description. Their status is not reported in the registry record. As a result, the posted information supports a description of the safety-population endpoint and the stated missing-data approach, but not a broader assessment of all planned analyses or robustness checks.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: injury/stab wound (4.2%).

The serious adverse event summaries list 0 serious adverse events among 22 participants in the clobetasol propionate cream, 0.05% group, and 1 among 24 participants in the DFD06 Cream group. The registry lists 0 deaths in each group. These are descriptive counts for the recorded safety summaries; they do not establish a comparative safety effect, particularly when the number of serious events is small.

The registry also lists “Injury/Stab Wound” as a top serious event term, with 4.2%. The record does not specify the group attribution for this term in the information reported, so it should not be assigned to either arm. The “other” adverse event counts are 11 for clobetasol propionate cream, 0.05%, and 5 for DFD06 Cream; these are separate from the serious adverse event counts and should not be conflated with them.

In general, adverse event summaries describe events recorded during a study and do not by themselves establish that a study product caused an event. The registry excerpt does not provide event narratives, timing, relatedness assessments, or a detailed breakdown of the non-serious events. These counts should therefore be read as registry safety summaries, not as a complete account of the nature or cause of every event.

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

The posted primary endpoint shows HPA axis suppression in 36.4% of the clobetasol propionate cream, 0.05% safety group and 12.5% of the DFD06 Cream safety group at Day 15. The counts are 8 of 22 and 3 of 24. The unadjusted re-calculation estimates a negative risk difference for DFD06 Cream relative to clobetasol propionate cream, 0.05%, but the interval extends from negative to positive values. The observed difference is therefore uncertain in direction and magnitude under that calculation.

The registry’s own analysis is labelled an ANOVA equivalence analysis and reports p = 0.086. The registry does not post its effect estimate, interval, or equivalence margin. The posted p-value cannot, without those details, be treated as proof that the products are equivalent. Likewise, the unadjusted p-value of 0.058 is not a probability that either treatment is effective, and it does not establish the absence or presence of a clinically important difference.

These results concern one safety endpoint measured at Day 15, in the stated safety population, after twice-daily application for 15 days. They do not report psoriasis response, longer-term outcomes, or the primary purpose’s systemic absorption question. No secondary outcome result is posted in the registry record. The short-term endpoint should not be extended to claims about outcomes beyond the recorded measure and timeframe.

The record also does not give the cortisol threshold used to define HPA axis suppression, detailed missingness information, or enough analysis detail to reconstruct the sponsor’s equivalence assessment. Those omissions limit clinical and statistical interpretation. The findings are best read as the observed safety-population rates accompanied by substantial uncertainty in the unadjusted comparison, alongside a sponsor-reported analysis whose key equivalence details are not available.

17. Why This Trial Matters Statistically

This trial illustrates how a safety endpoint can be summarized as an event percentage and compared in more than one statistical framework. The arm percentages give an accessible description of the observed HPA axis suppression results, while the risk difference, risk ratio, and odds ratio express comparisons on different scales. Seeing those measures alongside their uncertainty helps prevent a single point estimate from carrying more meaning than the data support.

It also illustrates why the analysis label matters. The registry reports an ANOVA equivalence analysis, while the recalculation is an unadjusted comparison of binary event proportions. Equivalence is not simply the opposite of finding a statistically significant difference: it depends on a prespecified margin and suitable analysis. Since the margin and sponsor estimate are not posted, the reported equivalence p-value cannot be interpreted as a fully documented equivalence conclusion.

The result also highlights the importance of defining the analysis population and missing-data approach. The endpoint uses the safety population, and the registry says missing safety data were not imputed. That information is essential context for the percentages, but the absence of details about missing endpoint measurements limits the assessment of how complete the endpoint data were.

Finally, the trial demonstrates the distinction between observed results and planning illustrations. The sample-size figures are based on the observed effect under stated assumptions; they are not the original design rationale or observed power. Keeping those roles separate supports more accurate interpretation of both the completed study and possible future planning.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record leaves several trial-specific details unavailable. It does not report the cortisol threshold or full operational definition used to classify HPA axis suppression. Without that information, the endpoint cannot be independently reconstructed from laboratory values, and the clinical meaning of the classification cannot be assessed in further detail.

The study was open-label, with masking listed as none. The primary outcome is based on a physiological test, but the registry record does not describe who assessed or classified the test result, or whether those assessments were blinded. Randomization is recorded, but the method for generating the allocation sequence and concealing it is not reported. These details prevent a fuller appraisal of potential sources of bias.

The primary endpoint was assessed at Day 15 after 15 days of twice-daily application. The record does not provide later endpoint measurements, so it cannot address persistence or longer-term outcomes. Although systemic drug absorption is part of the study purpose, no secondary result for that question is posted. The registry also does not post a psoriasis efficacy outcome.

The sponsor’s analysis is identified as ANOVA for equivalence, but its estimate, interval, equivalence margin, and model details are not reported. The number and pattern of missing endpoint values are also not reported, although the record states that no imputation was made for missing safety data. The registry does not explain the difference between total enrollment and the endpoint arm counts. These limitations mean the posted results support description of the recorded endpoint and calculations, but not a complete reconstruction of the protocol or analysis.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: DFD06 Cream vs Clobetasol Propionate Cream, 0.05% Hypothalamic- Pituitary-Adrenal (HPA) Axis Suppression Study in Patients With Moderate to Severe Plaque Psoriasis — NCT02131324.
• Registry record last updated 2018-05-18; status last verified 2018-04.
• Results first posted 2018-04-18.
• 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.

22. Record Summary

NCT02131324 is a completed randomized, open-label, parallel-group Phase 2 study sponsored by Promius Pharma, LLC. It enrolled participants with moderate to severe plaque psoriasis and compared DFD06 Cream with clobetasol propionate cream, 0.05%, each applied twice a day for 15 days. The primary endpoint was the percentage with HPA axis suppression at Day 15, assessed using serum cortisol after a cosyntropin (ACTH) test.

The safety-population results were 12.5% (3 of 24) for DFD06 Cream and 36.4% (8 of 22) for clobetasol propionate cream, 0.05%. The registry reports an ANOVA equivalence analysis with p = 0.086. An unadjusted re-calculation reports a risk difference of -0.239, interval limits of -0.479 and 0.002, and p = 0.058. The registry record does not provide the sponsor analysis’s equivalence margin or effect estimate. The results describe this endpoint and timeframe and do not establish outcomes beyond those reported.