Efficacy and Safety of Calcipotriol Plus Hydrocortisone Ointment Compared With Tacalcitol Ointment in Patients With Psoriasis on the Face and Skin Folds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Calcipotriol Plus Hydrocortisone Ointment Compared With Tacalcitol Ointment in Patients With Psoriasis on the Face and Skin Folds (NCT00640822), a randomized phase 3 study. The primary outcome is Subjects With Controlled Disease According to the Investigator Assessment of the Face at Week 8.

2. Clinical Question

The clinical question is about a specific outcome and site: investigator-assessed control of psoriasis on the face at Week 8. It is not a measure of disease across the whole body, nor does it directly summarize every symptom or sign in the face and skin folds. The registry record also lists secondary assessments of disease severity and signs on the face and intertriginous areas, as well as relapse and rebound. Results for those secondary outcomes are not reported in the registry record.

The trial compared the active combination ointment with both tacalcitol ointment and the vehicle. These are separate comparisons against the vehicle group, not a single combined comparison. The registry record gives counts for each group and unadjusted comparison summaries. It does not report the specific threshold or scoring rule used to classify facial disease as controlled, so the clinical meaning of that category cannot be made more precise from the record alone.

3. Trial Design

This was a randomized, single-masked, parallel-group Phase 3 study sponsored by LEO Pharma. The registry record describes 782 enrolled participants with psoriasis vulgaris. Participants were assigned to one of three groups: calcipotriol plus hydrocortisone ointment, tacalcitol ointment, or the calcipotriol-plus-hydrocortisone ointment vehicle. Each was applied once daily for up to 8 weeks. The record identifies the study as completed.

The primary endpoint was assessed at Week 8 and counted participants whose facial disease was judged controlled by the investigator. The posted outcome counts are 183 of 322 in the combination ointment group, 147 of 317 in the tacalcitol group, and 37 of 102 in the vehicle group. The endpoint counts and the safety denominators are not identical in every group; the registry record does not explain the difference or specify how participants with missing Week 8 assessments were handled.

Single masking is recorded, but the registry record does not identify which people were masked or describe how masking was maintained. It also does not report the randomization procedure, allocation concealment, stratification factors, or the planned allocation ratio. The observed group sizes therefore describe the posted outcome data; they do not establish the planned allocation scheme.

The study’s start is recorded as 2008-02 and its primary completion as 2009-06. Its stated focus was treatment of psoriasis on the face and intertriginous areas, which are sensitive sites. Although the record lists seven secondary outcomes, it gives no analysis results for them. Detailed eligibility criteria, follow-up procedures, adherence information, and the trial’s original statistical plan are not reported in the registry record.

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: Forty-one subjects were not randomised. Most we screen failures or did not have the required extent of disease or withdrew before randomization

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 Subjects With Controlled Disease According to the Investigator Assessment of the Face at Week 8, measured over Week 8.

The primary endpoint counts participants whose facial psoriasis was classified as controlled by the investigator at Week 8. It is a binary outcome at the participant level: each participant is counted as having controlled disease or not having controlled disease for this endpoint. The registry record gives the number classified as controlled and the number contributing to each group’s posted result.

A binary endpoint can provide an interpretable summary of how often a specified status was reached in each group. Comparing the group counts can describe whether the proportion classified as controlled differed between the study groups. Here, the posted counts are 183 of 322 for calcipotriol plus hydrocortisone, 147 of 317 for tacalcitol, and 37 of 102 for vehicle.

The outcome is restricted to the face and to the Week 8 assessment. It does not, by itself, capture the degree of change in an individual participant, the course of disease after that assessment, or results on the intertriginous areas. The registry record does not provide the investigator’s detailed criteria for “controlled disease,” how borderline assessments were classified, or how missing assessments were treated. Those details are important for understanding exactly what the endpoint represents and how consistently it was applied.

7. Results Posted in the Registry

• Calcipotriol Plus Hydrocortisone Ointment: 56.8% (183/322) versus 36.3% (37/102) on control; risk difference 20.6 percentage points (95% CI 9.8 to 31.3), risk ratio 1.57 (1.19–2.06); unadjusted two-proportion z-test p = <0.001.
• Tacalcitol Ointment: 46.4% (147/317) versus 36.3% (37/102) on control; risk difference 10.1 percentage points (95% CI -0.7 to 20.9), risk ratio 1.28 (0.96–1.70); unadjusted two-proportion z-test p = 0.074.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: the record counts participants assessed as having controlled facial disease at Week 8. For each group, the count of participants with controlled disease is interpreted relative to the number contributing to the posted endpoint. The outcome summary therefore concerns the proportion with the specified status, rather than a continuous score or the amount of change in a score.

What does a risk difference describe?

A risk difference is the difference between the proportions with an outcome in two groups. It is an absolute measure, expressed on the proportion scale. A value of zero represents equal observed proportions; a positive value means the outcome was more frequent in the first group named in the comparison than in the reference group. The posted risk difference for combination ointment versus vehicle is 0.206. For tacalcitol versus vehicle it is 0.101. These are unadjusted comparisons based on the posted group summaries.

The confidence interval gives a range of values compatible with the data under the calculation’s assumptions. Its width conveys precision: a narrower interval represents less uncertainty in the estimated difference, while a wider interval represents more. For combination ointment versus vehicle, the interval is 0.098 to 0.313. For tacalcitol versus vehicle, it is -0.007 to 0.209. The latter spans zero, while the former does not. This is a description of the intervals; the registry record does not report a full account of the inferential methods used in the trial’s own analysis.

How should the p-values be read?

The posted p-values are unadjusted: <0.001 for combination ointment versus vehicle and 0.074 for tacalcitol versus vehicle. In general, a p-value describes how inconsistent the observed data, or data more extreme, would be with a specified null model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry record does not report whether the trial’s sponsor used these calculations as its primary inferential analysis.

What do relative measures add?

The posted summaries also include risk ratios and odds ratios. A risk ratio compares the proportions with the outcome between groups, while an odds ratio compares the odds. They express relative rather than absolute contrasts, and their numerical scale differs from that of a risk difference. For combination ointment versus vehicle, the risk ratio is 1.567, with an interval from 1.191 to 2.061, and the odds ratio is 2.313, with an interval from 1.46 to 3.664. For tacalcitol versus vehicle, the risk ratio is 1.278, with an interval from 0.963 to 1.697, and the odds ratio is 1.519, with an interval from 0.959 to 2.406. These summaries do not replace the absolute counts, and the registry record does not describe an adjusted model behind them.

Why do the counts and group sizes matter?

The estimated contrasts depend on the observed outcome counts and the participants represented in each group. The primary outcome counts are 183 of 322, 147 of 317, and 37 of 102. The vehicle group is smaller than either active-treatment group, which contributes to uncertainty in comparisons involving that group. The confidence intervals express sampling uncertainty, but they do not account for possible bias from missing data, outcome classification, or other design limitations.

The sample-size figures are planning illustrations based on the observed effects, not results of the trial’s original design calculation. They assume two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. Smaller target effects require more participants because distinguishing a smaller difference from random variation generally requires more information. The original trial’s sample-size assumptions and detailed analysis methods are not reported in the registry record.

For outcomes that are counts of participants with an event, the planning entries are participants per arm. A separate convention applies to time-to-event planning, where figures are total events; the primary outcome in this study is binary, not time-to-event. These planning results are not observed power and should not be read as a retrospective measure of whether the trial had adequate power.

10. Confidence Intervals and Precision

Precision is reflected in the uncertainty around an estimate, not just in the estimate itself. The confidence interval for the combination ointment versus vehicle risk difference runs from 0.098 to 0.313. It lies above zero, indicating that the range of values represented by this interval does not include no difference. The interval nevertheless covers a range of magnitudes, so the point estimate should not be treated as exact.

For tacalcitol versus vehicle, the risk-difference interval runs from -0.007 to 0.209. It includes zero, so the data are compatible with no difference as well as with a positive difference over the interval’s range. The p-value of 0.074 is consistent with that uncertainty. Neither the p-value nor the interval says whether a difference would matter clinically; the registry record does not report a threshold for clinical importance.

Both comparisons use a vehicle group with 102 participants in the primary outcome summary. The active groups have 322 and 317 participants, respectively. The difference in group sizes and the outcome counts contribute to the amount of information in each comparison. A confidence interval reflects statistical uncertainty under its calculation, but it does not address all possible sources of uncertainty, including bias from missing assessments or problems in outcome measurement.

The registry record reports confidence intervals for the comparison summaries but does not give the method used to construct them or describe adjustments for other outcomes or comparisons. The intervals should therefore be read as posted estimates of precision, not as a complete account of every uncertainty affecting the trial’s interpretation.

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 sample-size entries are planning illustrations for two-arm comparisons based on the observed effect, not the trial’s original design calculation. The trial’s own sample-size justification and design assumptions are not reported in the registry record. The illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect.

For this binary outcome, the figures mean participants per arm. The separate rule for time-to-event outcomes is to report total events, but that does not apply to the primary endpoint in this trial. In the 80% power column, the planned group size is the number of participants per arm under the listed assumptions to give the study an 80% chance of detecting the target effect if that effect is the true one. The 90% power column uses a higher chance of detection, which generally requires more participants under otherwise comparable assumptions.

Rows that plan for a smaller fraction of the observed effect require more participants per arm than rows planning for the full observed effect. This reflects a general statistical principle: smaller differences are harder to distinguish from random variation, so more information is needed. The illustrations use equal group sizes even though the observed primary outcome group sizes were unequal.

These figures are not observed power. They are prospective-style calculations using effects derived from the observed results; they do not report the probability that the completed trial was successful, nor do they establish the original trial’s planning rationale. Any curve associated with these scenarios should be read as a visualization of the same planning relationship, not as a separate clinical result.

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 = 0.363; treatment proportion p₁ = 0.568; average p̄ = 0.466.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7054 = 1.3826.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6903 = 0.5810.
4. n = (1.3826 + 0.5810)² / (0.2056)² = 91.2, rounded up to 92 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 <- 0.362745098039216                          # control proportion
p1 <- 0.56832298136646                          # 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(640822)
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 = 92 (80% power), 122 (90% power)
 75% of observed effect: n per arm = 162 (80% power), 216 (90% power)
 50% of observed effect: n per arm = 360 (80% power), 481 (90% power)
power.prop.test: 91.2 
Simulated power at n = 92 per arm: 0.797 (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. Multiplicity, Missing Data and Analysis Populations

The registry record lists seven secondary outcomes, including investigator assessments of overall disease severity and sign scores for the face and intertriginous areas, as well as relapse and rebound outcomes. It reports no analysis results for these outcomes. Their results, estimates, uncertainty measures, and analysis populations are therefore not reported in the registry record.

The two posted primary-outcome comparisons both use the vehicle group as the reference. The registry record does not report whether multiplicity was considered, whether a testing hierarchy was planned, or whether any adjustment was made for multiple comparisons or secondary outcomes. The unadjusted p-values should consequently be understood as unadjusted, rather than as evidence that a family-wise error procedure was used.

Information about missing primary endpoint data is also not reported in the registry record. The posted group sizes for the primary outcome are 322, 317, and 102, while the safety denominators are 321, 316, and 102. The record does not explain why the endpoint and safety denominators differ in the two active-treatment groups. It does not describe exclusions, withdrawals, imputation, or sensitivity analyses for missing data.

The analysis population is not reported in the registry record. It is not clear from the posted results whether the primary analysis included all randomized participants, only participants with an observed Week 8 assessment, or another defined group. The statistical analysis plan, covariate adjustment, handling of protocol deviations, and any interim analyses are also not reported. These omissions limit assessment of the prespecified analysis strategy and the robustness of the posted estimates.

14. Safety Results

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

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: abscess limb (1.0%), pregnancy (1.0%), disorientation (1.0%), thrombosis (1.0%), hip arthroplasty (0.3%).

The posted safety summary lists serious adverse events for 5 of 321 participants receiving calcipotriol plus hydrocortisone ointment, 3 of 316 receiving tacalcitol ointment, and 4 of 102 receiving vehicle. The other-adverse-event counts are 13 of 321, 30 of 316, and 2 of 102, respectively. These are counts of affected participants and their stated denominators; they should be read within each treatment group rather than as comparisons adjusted for differences in group size.

The record lists serious adverse event terms including abscess limb, pregnancy, disorientation, thrombosis, hip arthroplasty, and myocardial infarction, with the listed values ranging from 0.3% to 1.0%. It does not provide enough detail in the posted summary to assign each listed term to a specific treatment group or to establish relatedness to treatment. Deaths are not reported in the registry record.

Adverse-event counts describe events recorded during the study; by themselves they do not show that a treatment caused an event or establish comparative safety. The registry record does not provide fuller event narratives, exposure-adjusted rates, or a detailed account of how events were collected and classified.

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

The posted primary outcome describes investigator-assessed control of facial disease at Week 8. The combination ointment group had 183 participants classified as controlled among 322, and the vehicle group had 37 among 102. The posted unadjusted risk difference and its confidence interval indicate a positive difference for that comparison, with an unadjusted p-value of <0.001. The tacalcitol-versus-vehicle estimate is also positive, but its confidence interval includes zero and its unadjusted p-value is 0.074.

These findings do not establish what would happen for every participant, for disease at other body sites, or after the Week 8 assessment. They are limited to the recorded endpoint, trial population, and posted analysis. The trial also listed secondary outcomes on severity and signs at the face and intertriginous areas and on relapse and rebound, but their results are not reported in the registry record. The primary result therefore cannot substitute for those outcomes.

The results do not provide a direct statistical comparison of the combination ointment with tacalcitol. Separate comparisons of each group with vehicle do not establish whether the two active-treatment groups differ from one another. No such direct contrast is reported in the registry record.

The endpoint’s operational definition, missing-data handling, analysis population, and full analysis plan are not reported. Those omissions matter when judging how broadly to interpret the estimates. The results describe the posted counts and unadjusted comparisons; they do not by themselves establish clinical importance, durability, or a causal explanation for any difference.

16. Why This Trial Matters Statistically

This trial illustrates why absolute group counts, effect estimates, and uncertainty intervals should be considered together. The numbers classified as controlled are meaningful only alongside their group denominators. The risk difference provides an absolute comparison, while the risk ratio and odds ratio provide relative summaries on different scales. Looking at these measures together helps distinguish the size and direction of a contrast from the degree of uncertainty around it.

The two comparisons against vehicle also illustrate that estimates can have different levels of precision. The combination-versus-vehicle interval lies above zero, while the tacalcitol-versus-vehicle interval includes zero. Reporting only the point estimates would obscure that distinction; reporting only the p-values would hide the range of effects compatible with the data. Neither form of summary alone describes clinical importance.

The record also demonstrates the importance of transparent reporting beyond the primary endpoint. Seven secondary outcomes are listed, but their results are not reported. Details about multiplicity, missing data, the analysis population, and the original statistical plan are likewise absent. Without those details, readers cannot fully evaluate the analysis strategy or determine how the primary comparisons fit into the broader set of planned questions.

Finally, planning illustrations based on observed effects should not be mistaken for the trial’s original design rationale or for observed power. Clear separation between completed-study results and hypothetical planning scenarios helps prevent retrospective calculations from being interpreted as evidence that a design was adequately powered.

17. 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 registry record does not specify the rule used to classify facial disease as controlled, the assessor procedures, or the treatment of missing Week 8 assessments. This makes it difficult to determine exactly how the primary status was operationalized and whether all participants were assessed consistently. The analysis population is not reported, and the record does not explain the difference between the primary outcome group sizes and the safety denominators in the active groups.

Although the study is described as randomized and single-masked, the registry record does not say who was masked or describe the randomization and allocation procedures. It does not report the original sample-size justification, a detailed statistical analysis plan, multiplicity handling, interim analyses, or any adjusted analyses. The posted comparisons are unadjusted, and a direct comparison between the two active-treatment groups is not reported.

The registry record lists secondary outcomes but gives no results for them, limiting assessment beyond the primary facial endpoint. It also does not provide detailed follow-up or adherence information, or explain how withdrawals and protocol deviations were handled. The safety summary gives counts, but does not provide event narratives, treatment relatedness, or deaths; deaths are not reported in the registry record.

These reporting gaps do not change the posted counts, but they constrain how fully the estimates can be interpreted. Conclusions should remain tied to the recorded Week 8 endpoint and the unadjusted comparisons available in the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy and Safety of Calcipotriol Plus Hydrocortisone Ointment Compared With Tacalcitol Ointment in Patients With Psoriasis on the Face and Skin Folds — NCT00640822.
• Registry record last updated 2025-03-07; status last verified 2015-04.
• Results first posted 2010-12-21.
• 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.

21. Record Summary

NCT00640822 is a completed randomized, single-masked, parallel-group Phase 3 study sponsored by LEO Pharma. It enrolled 782 participants with psoriasis vulgaris and compared once-daily calcipotriol plus hydrocortisone ointment, tacalcitol ointment, and vehicle, for up to 8 weeks. The primary endpoint was investigator-assessed control of facial disease at Week 8.

The posted primary outcome counts were 183 of 322 for combination ointment, 147 of 317 for tacalcitol, and 37 of 102 for vehicle. Unadjusted comparisons against vehicle are reported; their estimates and uncertainty differ, and no direct active-treatment comparison is posted. Secondary outcomes are listed without results. Details of the trial’s original statistical plan, analysis population, missing-data handling, and multiplicity procedures are not reported in the registry record.