Multicenter Study of the Safety and Efficacy of NAFT-500 in Tinea Cruris: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multicenter Study of the Safety and Efficacy of NAFT-500 in Tinea Cruris (NCT00750152), a randomized phase 3 study. The primary outcome is Percentage of Subjects.

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group study. Its official title describes a multicenter evaluation of the efficacy and safety of NAFT-500 in subjects with tinea cruris. The registry lists an enrollment of 334 and a completed study. The recorded study start was 2008-09 and the primary completion was 2009-08.

Participants were assigned to NAFT-500 or placebo. The two posted primary-outcome arms are labelled NAFT-500 and Placebo-2wks. The record does not describe the randomization procedure, allocation concealment, treatment schedule, or what the “2wks” in the comparator label means. The study is described as double-blind, but the registry record does not specify who was masked or how masking was maintained.

The primary endpoint was assessed at Week 4 post-baseline. The registry describes the efficacy population as a subset of the Safety Evaluation Set: subjects had to have a positive baseline culture and an available primary efficacy variable. It calls this a modified intent-to-treat principle and explains that culture results were not available before the start. The record does not give further detail about the timing or handling of those culture results.

The primary outcome is binary at the participant level: a subject either met the complete-cure definition or did not. Two outcome measures are recorded, with one secondary outcome posted: mycological cure and treatment effectiveness. The registry record does not provide the secondary outcome estimates in the registry record described for this analysis. Its reported primary analysis used a Cochran-Mantel-Haenszel test. Details of the test’s stratification factors and the broader statistical analysis 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS)is the subset of all subjects in the Safety Evaluation Set (SES)with a positive culture at baseline and for whom the primary efficacy variable is available. This is a modified intent-to-treat (MITT) principle because the culture results were not available before the start of treatment.

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 Percentage of Subjects, measured over Week 4 post-baseline.

The primary endpoint is the percentage of subjects with complete cure at Week 4 post-baseline. The registry defines complete cure using both laboratory and clinical criteria: central-laboratory dermatophyte culture and KOH results had to be negative, and erythema, scaling, and pruritus each had to be absent, with a grade of 0 on the stated five-point severity scale. The scale runs from absent through marked, with “not done” also listed as a grade.

Combining mycology with the three symptom or sign assessments makes this a stringent composite endpoint: all the specified conditions must be met for a subject to count as completely cured. The endpoint therefore differs from measuring only a change in one symptom or only a laboratory result. Because it is recorded as a percentage of subjects meeting a yes-or-no definition, the group outcome is binary and can be expressed as a proportion or percentage.

In general, a prespecified primary endpoint gives a trial a principal outcome for evaluating its central research question. A composite can capture more than one aspect of a condition, but its interpretation depends on the exact components and rules used to define success. Here those rules are stated in the registry, and the assessment time is Week 4 post-baseline. Longer-term outcomes and the endpoint’s behavior at other time points are not reported in the registry record.

7. Results Posted in the Registry

• NAFT-500: 25.3% (19/75) versus 2.8% (2/71) on control; risk difference 22.5 percentage points (95% CI 11.9 to 33.1), risk ratio 8.99 (2.17–37.22); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level result: complete cure or not complete cure at Week 4 post-baseline. The posted arm percentages describe the fraction meeting the endpoint. The underlying counts are 19 of 75 in the NAFT-500 arm and 2 of 71 in the placebo arm. These are the counts used for a simple unadjusted re-calculation. The efficacy analysis population is the Full Analysis Set, defined in the registry by baseline culture and availability of the primary efficacy variable.

What does a risk difference describe?

In general, a risk difference subtracts one group’s event proportion from the other group’s event proportion. It expresses the absolute separation between groups on the outcome scale. Here the unadjusted re-calculated risk difference is 0.225. The direction is consistent with a higher posted complete-cure percentage in the NAFT-500 arm than in the placebo arm. The risk difference does not adjust for any covariates or strata, and the registry record does not say that the re-calculation uses the sponsor’s adjustment method.

What does the confidence interval add?

In general, a confidence interval gives a range of values compatible with a particular estimation procedure and its assumptions. It conveys uncertainty around an estimate rather than just a single point estimate. The unadjusted 95% confidence interval for the risk difference is 0.119 to 0.331. It belongs to the simple re-calculation, not the sponsor’s CMH analysis. A confidence interval does not remove uncertainty about population selection, measurement, missing outcomes, or the applicability of the trial results beyond the analyzed participants.

Why can analyses of the same trial differ?

The registry records a Cochran-Mantel-Haenszel analysis for the sponsor’s comparison and a one-sided p-value of 0.001, alongside p=0.025. The simple re-calculation uses the posted summary counts without adjustment and gives an unadjusted p-value of <0.001. In general, a CMH test can compare groups while accounting for defined strata. The registry record does not report which strata were used, whether other adjustments were made, or the full details needed to recreate the sponsor’s test. Differences between methods and analysis specifications can therefore lead to different inferential results. Because a discrepancy is flagged, the sponsor’s own analysis takes precedence as the trial’s reported analysis.

What does over-dispersion mean in general?

In general, over-dispersion occurs when the variability in data is greater than a model assumes. It can affect standard errors and the reliability of tests or intervals if the model does not account for it. The primary endpoint is binary, and the registry record does not report an over-dispersion assessment or a model-based analysis of the binary outcome. This general concept should not be read as a claim that over-dispersion occurred in this trial.

What is known about the analysis population?

The Full Analysis Set is described as a subset of the Safety Evaluation Set with a positive culture at baseline and an available primary efficacy variable. The registry calls this a modified intent-to-treat principle and notes that culture results were not available before the start. The record does not provide a participant flow, the number excluded from the efficacy analysis, or a detailed account of missing primary outcomes. It also does not explain whether missing values were imputed or how other protocol deviations were handled. These omissions limit assessment of the consequences of the population definition and missing data.

The registry lists one secondary outcome, mycological cure and treatment effectiveness, but estimates and analysis details for that outcome are not reported in the registry record. The number of outcome measures and analyses recorded does not establish that every planned analysis was posted. The statistical plan, including any prespecified covariates, multiplicity procedure, or interim analyses, is not reported in the registry record.

10. Confidence Intervals and Precision

The unadjusted re-calculated risk difference is 0.225, with a 95% confidence interval from 0.119 to 0.331. The interval describes the precision of that simple comparison under its calculation method. It is not a confidence interval for the sponsor’s CMH analysis, and the registry record does not report a confidence interval for that analysis.

In general, a confidence interval is more informative than a point estimate alone because it shows a range of uncertainty around the estimate. A narrower interval indicates greater statistical precision under the method used; a wider interval indicates less precision. The interval should not be interpreted as covering every source of uncertainty. It does not account for possible selection effects, measurement issues, missing outcomes, or limits on generalizability unless those are built into the analysis, and the registry record does not describe such adjustments for this re-calculation.

The observed counts are 19 of 75 for NAFT-500 and 2 of 71 for placebo. The relatively limited number of complete-cure observations, particularly in the placebo arm, is relevant context when interpreting an estimate and its uncertainty. No further precision measure for the posted percentages is reported in the registry record. The sponsor’s analysis is distinct: the record gives its test results but no corresponding interval estimate. Thus, readers should keep the unadjusted estimate and interval separate from the sponsor’s reported inferential 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 participants per arm, not total events. They are illustrative calculations based on the observed effect rather than the original trial design. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The original design assumptions and the trial’s sample-size justification are not reported in the registry record.

For planning based on 100% of the observed effect, the figures are 37 participants per arm for 80% power and 49 participants per arm for 90% power. For planning for 75% of the observed effect, they are 54 participants per arm for 80% power and 72 participants per arm for 90% power. For planning for 50% of the observed effect, they are 95 participants per arm for 80% power and 127 participants per arm for 90% power.

In general, power is the probability that a planned study will detect an effect of the specified size under the chosen assumptions if that effect is present. The 80% and 90% columns indicate different target probabilities for detecting the assumed effect. A smaller target effect requires more participants to detect reliably under otherwise unchanged planning assumptions. These figures are planning illustrations, not observed power; they do not describe the probability that this completed trial’s finding is true or that it would be reproduced.

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 = 0.028; treatment proportion p₁ = 0.253; average p̄ = 0.141.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4918 = 0.9639.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4653 = 0.3916.
4. n = (0.9639 + 0.3916)² / (0.2252)² = 36.2, rounded up to 37 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 <- 0.028169014084507                          # control proportion
p1 <- 0.253333333333333                          # 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(750152)
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 = 37 (80% power), 49 (90% power)
 75% of observed effect: n per arm = 54 (80% power), 72 (90% power)
 50% of observed effect: n per arm = 95 (80% power), 127 (90% power)
power.prop.test: 36.2 
Simulated power at n = 37 per arm: 0.875 (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 sponsor’s reported primary analysis used a Cochran-Mantel-Haenszel test. The registry lists a one-sided p-value of 0.001 and also reports p=0.025. It does not provide a confidence interval for this analysis or enough detail about its strata and other specifications to reproduce the result. The meaning of the separately listed p-value is not explained in the registry record.

A simple unadjusted re-calculation from the posted summary counts gives a risk difference of 0.225, a 95% confidence interval from 0.119 to 0.331, and an unadjusted p-value of <0.001. This calculation is not a substitute for the sponsor’s analysis: it does not use the stated CMH method and is not adjusted for any strata. The registry record flags a discrepancy between the sponsor analysis and the re-calculation. In that situation, the sponsor’s own analysis takes precedence as the trial’s reported result.

The difference should be handled transparently rather than resolved by selecting whichever result appears more favorable. The two analyses answer the comparison using different reported approaches, and the available registry entries do not establish why their p-values differ. The reported treatment contrast and the sponsor’s inferential analysis should therefore be distinguished when interpreting the posted results.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint of complete cure and one secondary outcome, mycological cure and treatment effectiveness. It also records two outcome measures and one analysis. These entries do not establish the complete set of outcomes or tests that may have been planned. A multiplicity strategy for addressing the possibility of multiple comparisons is not reported in the registry record.

In general, when researchers test multiple outcomes, time points, subgroups, or treatment contrasts, the chance of obtaining at least one small p-value by chance can increase. Statistical plans may address this through prespecified testing sequences or adjustments, but no such approach is described in the registry record. The record does not state whether there were interim analyses, subgroup analyses, or other comparisons beyond those listed. Their presence or absence should not be inferred.

The primary efficacy population was the Full Analysis Set, described as a subset of the Safety Evaluation Set requiring a positive baseline culture and an available primary efficacy variable. The record calls this a modified intent-to-treat principle. It does not report how many participants were excluded from that population or provide a participant flow explaining exclusions and outcome availability. The definition therefore gives useful eligibility criteria for the analysis but does not permit a full assessment of how the analyzed population relates to all randomized participants.

Missing-data methods are not reported in the registry record. In particular, the record does not say whether missing endpoint values were imputed, treated as non-cures, or excluded beyond the stated availability requirement. The handling of protocol deviations and the timing of baseline culture results are also not described in detail. These details matter because choices about inclusion and missing outcomes can influence an estimated treatment contrast. No conclusion about the direction or size of any such influence can be drawn from the information recorded.

The registry describes the Full Analysis Set as modified intent-to-treat because culture results were not available before the start. The additional detail about what “the start” refers to is not reported in the registry record. Accordingly, the population definition can be repeated, but its operational consequences and alignment with the planned analysis cannot be fully evaluated.

15. 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 1% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event summary records 0 affected participants among 166 at risk in the NAFT-500 group and 0 among 168 at risk in the Placebo-2wks group. The registry lists no top serious adverse event terms. These are the serious adverse event figures recorded for the groups; they do not describe every aspect of safety or establish that no adverse events of any kind occurred.

For other adverse events, the record lists 4 affected among 166 at risk in the NAFT-500 group and 10 among 168 at risk in the Placebo-2wks group. The registry does not provide further definitions or event terms in the registry record recorded for this summary, so these figures should be interpreted only as the posted “other” adverse event counts. The counts are separate from the serious adverse event counts.

Deaths are not reported in the registry record. The at-risk counts are safety-summary denominators and should not be substituted for the efficacy analysis denominators. These safety figures are descriptive; the registry information does not provide a statistical comparison of adverse events or enough detail to assess event timing, severity, or causality.

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

The posted primary outcome describes complete cure at Week 4 post-baseline among the efficacy population defined in the registry. The recorded percentages are 25.3% for NAFT-500 and 2.8% for placebo. The unadjusted re-calculation reports a risk difference of 0.225, with a 95% confidence interval from 0.119 to 0.331 and an unadjusted p-value of <0.001. The sponsor’s own analysis is reported separately and takes precedence because the record flags a discrepancy.

This finding is specific to a trial population with tinea cruris, the complete-cure definition, the assessment at Week 4 post-baseline, and the analysis population recorded in the registry. It does not establish the results at other time points, the durability of complete cure, or outcomes for participants without an available primary efficacy variable or without a positive baseline culture. Longer-term results and the detailed secondary-outcome results are not reported in the registry record.

In general, statistical significance and clinical importance are different questions. A p-value addresses evidence against a statistical null under a particular analysis; it does not by itself establish whether an effect matters to patients or clinicians. The registry information does not provide a threshold for clinical importance, and the reported endpoint does not capture every possible benefit or harm. Safety counts should be considered independently rather than inferred from the efficacy result.

The trial record also does not provide enough information to evaluate all design and analysis choices, including the original sample-size justification, missing-data handling, multiplicity procedures, or the CMH test’s detailed specifications. The results should therefore be read as a comparison of the posted endpoint in the recorded analysis population, with the stated methodological and reporting limits, rather than as a complete account of every possible outcome or uncertainty.

17. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition matters. Complete cure was not simply a negative laboratory result or improvement in one symptom: it required negative central-laboratory mycology results and absence of erythema, scaling, and pruritus, all assessed at Week 4 post-baseline. The percentage therefore represents a composite, all-criteria outcome. Interpretation depends on both the clinical and laboratory components and on the recorded analysis population.

It also illustrates the difference between a posted group comparison and the analysis used by the sponsor. The simple unadjusted re-calculation from the summary counts gives an estimate, interval, and p-value, whereas the sponsor reported a CMH test. The registry flags a discrepancy, and the sponsor’s own analysis takes precedence. Without the full statistical plan and test specifications, the reason for the difference cannot be established from the registry record.

Finally, the record shows how estimates, precision, planning calculations, and safety summaries answer different questions. The confidence interval describes uncertainty for the unadjusted estimate; the sample-size figures are planning illustrations rather than observed power; and adverse event counts are descriptive safety information, not evidence about the efficacy endpoint. Keeping these quantities separate helps avoid overstating what any one result establishes.

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 gives limited detail about the trial’s statistical plan. The original sample-size justification, randomization procedure, allocation concealment, masking procedures, and interim analysis plans are not reported in the registry record. The CMH test is named, but its strata and other analysis specifications are not provided. These gaps prevent a full reconstruction of the sponsor’s reported analysis.

The primary efficacy population required a positive baseline culture and an available primary efficacy variable. The record does not provide participant flow or the number excluded from this population, nor does it describe how missing primary outcomes or protocol deviations were handled. The explanation that culture results were not available before the start is not elaborated further. These limitations affect how fully the efficacy analysis population can be assessed.

The registry records one secondary outcome but does not provide its estimates in the registry record recorded for this analysis. A multiplicity procedure is not reported, and the record does not clarify whether additional outcomes or subgroup analyses were planned. The sponsor’s reported analysis has no confidence interval listed, and a separately reported p-value is not explained. The simple unadjusted re-calculation is therefore useful as a distinct descriptive comparison but cannot resolve those reporting gaps.

The safety summary gives counts for serious and other adverse events, but deaths are not reported in the registry record. Event terms, timing, severity beyond the serious-event classification, and causal assessments are not available in the recorded details. The endpoint is assessed at Week 4 post-baseline, so the posted primary result does not describe outcomes at later times. These limitations restrict the scope of interpretation without determining the direction of any potential bias.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Multicenter Study of the Safety and Efficacy of NAFT-500 in Tinea Cruris — NCT00750152.
• Registry record last updated 2013-04-22; status last verified 2012-10.
• Results first posted 2012-03-13.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT00750152 is a completed, randomized, double-blind, parallel-group phase 3 study of NAFT-500 and placebo in subjects with tinea cruris. The registry lists enrollment of 334, a study start of 2008-09, and primary completion in 2009-08.

The primary endpoint was the percentage of subjects with complete cure at Week 4 post-baseline, using negative central-laboratory mycology results and absence of erythema, scaling, and pruritus. The posted percentages were 25.3% for NAFT-500 and 2.8% for Placebo-2wks. The sponsor’s reported CMH analysis and the simple unadjusted re-calculation are distinct; because a discrepancy is flagged, the sponsor’s own analysis takes precedence.

The registry describes a modified intent-to-treat Full Analysis Set based on baseline culture and primary-outcome availability. Further details about missing data, multiplicity, the original sample-size plan, and the sponsor analysis are not reported in the registry record.