Evaluation of the Efficacy and Safety of NAFT-600 in Subjects With Tinea Pedis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Efficacy and Safety of NAFT-600 in Subjects With Tinea Pedis (NCT01290341), a randomized phase 3 study. The primary outcome is Complete Cure of Interdigital Tinea Pedis.

2. Clinical Question

3. Trial Design

The registry describes a Phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of NAFT-600 for tinea pedis. It is marked completed. Enrollment is listed as 860, and the record gives a start of 2011-02 and primary completion of 2011-11. The registry summary describes a 6-week study, while both topical groups are described as using their assigned product once daily for two weeks.

The intervention was NAFT-600, also identified as naftin 2 % gel. The comparator was placebo, described as vehicle. The parallel-group arrangement means participants were assigned to one of these groups rather than receiving both interventions in sequence. Double masking indicates that the record identifies the study as double-blind, but the specific masking procedures and who was masked are not reported in the registry record.

The primary endpoint was the percentage of subjects with complete cure of interdigital tinea pedis at Visit 4/Week 6. The definition combined mycological and clinical criteria: negative dermatophyte culture and KOH results, with no erythema, scaling, or pruritus. The registry also lists effective treatment and mycological cure of interdigital tinea pedis at Week 6 as a secondary outcome. The posted results record two outcome measures and one analysis.

The primary analysis population is described as the Full Analysis Set, a subset of the Safety Evaluation Set with positive mycology culture at baseline and an available primary efficacy variable. The registry calls this a modified intent-to-treat principle. It does not give a complete account of how unavailable outcomes were handled. Original design assumptions, including the trial's own sample-size justification and planned statistical details, 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: Full Analysis Set (FAS) defined as the subset of all subjects in the Safety Evaluation Set (SES) with a positive mycology culture at baseline and for whom the primary efficacy variable is available. This was a modified intent to treat 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.

Population: The Safety Evaluation Set (SES) which is the population of subjects who receive at least one dose of study medication is used.

6. Primary Endpoint

The registry lists the primary outcome as Complete Cure of Interdigital Tinea Pedis, measured over Visit 4/ Week 6.

The primary endpoint is the percentage of subjects with complete cure of interdigital tinea pedis at Visit 4/Week 6. Complete cure is a combined endpoint: mycology had to be negative by both dermatophyte culture and KOH, and erythema, scaling, and pruritus had to be absent. A participant meeting only the mycological criteria or only the clinical criteria would not meet the registry's stated definition.

Using both laboratory and clinical criteria makes the endpoint more specific to the combined state the trial set out to assess than either type of measure alone. This is a general statistical and measurement point, not a claim about how the endpoint performs in practice. Requiring several conditions also means that a change in any one component can affect whether the endpoint is met.

The outcome is binary at the participant level—complete cure or not—and is reported as a percentage. The primary comparison is therefore between the proportions meeting the definition in the two groups. The registry reports 26% for NAFT-600 and 3.3% for placebo. The analysis population is not every person enrolled by definition: it is described as participants in the Safety Evaluation Set who had a positive baseline mycology culture and an available primary efficacy measure. The registry record does not fully explain the handling of participants whose primary measure was unavailable.

7. Results Posted in the Registry

• NAFT-600: 26.0% (104/400) versus 3.3% (7/213) on control; risk difference 22.7 percentage points (95% CI 17.8 to 27.6), risk ratio 7.91 (3.75–16.70); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: each participant either met the registry's definition of complete cure or did not. For a binary endpoint, a group percentage describes the share of participants with the event of interest. The group results are 26% for NAFT-600 and 3.3% for placebo. The counts associated with the analysis are 104 of 400 and 7 of 213, respectively. Those denominators belong to the reported analysis and should not be substituted with the trial's enrollment figure.

What does the risk difference describe?

The risk difference compares event proportions by subtraction on the risk scale. The unadjusted recalculation reports 0.227, with an interval from 0.178 to 0.276. It gives an absolute contrast in the probability scale. This is distinct from a relative measure: the risk difference does not say how many times as common the outcome was in one group, and it is not itself a percentage printed in the registry.

How do relative measures differ?

The risk ratio compares the event proportion in one group with the proportion in the other. The recalculated risk ratio is 7.911, with an interval from 3.748 to 16.7. The odds ratio compares odds rather than probabilities; its recalculated estimate is 10.34, with an interval from 4.713 to 22.69. When an outcome is not rare, odds and probabilities can differ substantially as quantities, so an odds ratio should not be described as though it were a risk ratio. Here, each measure expresses the contrast on its own scale.

What does a p-value tell the reader?

The unadjusted recalculation reports p <0.001. The sponsor's reported analysis is identified as Cochran-Mantel-Haenszel and gives a p-value of 0.001; the record also lists p <0.025. In general, a p-value assesses how compatible data are with a null hypothesis under a specified model and its assumptions. It does not give the probability that the null hypothesis is true, and it does not quantify the clinical importance of an effect. A p-value also cannot resolve questions about missing data, endpoint validity, or selection into the analysis population.

The Cochran-Mantel-Haenszel method is generally used to compare categorical outcomes while accounting for strata. The registry identifies the method but does not report the strata or other implementation details. It is therefore appropriate to name the reported method without assuming which factors it adjusted for. The unadjusted recalculation is a separate comparison based on posted summary statistics and does not reproduce unreported modeling choices.

Why can over-dispersion matter?

For binary outcomes, a basic binomial model assumes that variation is consistent with the event probability and number of observations in each group. More general clustered, stratified, or otherwise dependent data can have more variation than a simple model allows. This is often called over-dispersion, and accounting for it can widen uncertainty or change a test result. This is a general explanation. The registry does not report an over-dispersion assessment or indicate that such a model was used; there is no basis in the record for claiming it was present in this trial.

What does the confidence interval add?

An interval around an estimate shows a range of values compatible with the data under the method used and its assumptions. In general, narrower intervals indicate greater precision and wider intervals indicate more uncertainty about the effect size. The recalculated risk-difference interval runs from 0.178 to 0.276. The registry does not identify a confidence level for this recalculated interval, so no confidence level should be assigned to it from the record alone. Intervals do not account automatically for all possible bias, and their interpretation depends on the analysis and data quality.

Because the endpoint is a proportion, the observed estimate is also sensitive to who is included and how the outcome is ascertained. The Full Analysis Set excludes, by its stated definition, people outside the Safety Evaluation Set, those without a positive baseline mycology culture, and those without an available primary efficacy variable. The registry record does not fully describe the missing-data procedure or report sensitivity analyses. These details matter because different analysis populations and assumptions about unavailable outcomes can affect the estimated comparison.

10. Confidence Intervals and Precision

The recalculated risk difference is 0.227, and its reported interval extends from 0.178 to 0.276. This interval expresses uncertainty around the estimated absolute contrast. Its width is relevant to precision: a more concentrated interval would indicate a more precise estimate under the same method, while a wider one would indicate less precision. The registry does not specify the confidence level for this recalculated interval, so it should not be labelled with a confidence level that is not stated.

The relative measures also have intervals. The risk ratio is 7.911, with an interval from 3.748 to 16.7. The odds ratio is 10.34, with an interval from 4.713 to 22.69. These intervals are on different scales from the risk-difference interval. Their endpoints should be interpreted according to the measure: the risk difference is an absolute contrast, while risk ratio and odds ratio are relative contrasts.

The posted outcome proportions are 26% in the NAFT-600 group and 3.3% in the placebo group, based on counts of 104 of 400 and 7 of 213. Uncertainty is affected by the amount of information in the analysis and by the event distribution. In general, sparse outcomes in a group can make relative-effect estimates less precise, and estimates can be especially sensitive to a small number of observed events. This is a general statistical consideration, not an additional trial finding.

Precision is not the same as validity. An interval can quantify sampling uncertainty under a method without accounting for selection, missing outcome data, measurement issues, or departures from model assumptions. The registry record does not fully report how missing primary outcomes were handled or the details needed to reconstruct the sponsor's analysis. The intervals should therefore be considered alongside the analysis population and the limitations of the record.

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. The planning illustration uses the observed effect as its reference and considers planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. At each of those effect assumptions, the entries for 80% power and 90% power describe the number of participants per arm needed under the stated illustration to have the corresponding probability of rejecting the null hypothesis if the assumed effect is true and the planning model applies.

The stated 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 the stated fraction of the observed effect. The trial's original design assumptions, including its own sample-size justification, are not reported in the registry record. These planning calculations are therefore not evidence of the assumptions used when the trial was designed.

For a fixed target power and significance level, planning for a smaller effect generally requires more participants because a smaller contrast is harder to distinguish from sampling variation. That general principle explains why the planning entries rise as the assumed effect fraction falls. The 90% power column targets a greater chance of detecting the assumed effect than the 80% power column, under the same planning framework, and consequently calls for more participants per arm.

The displayed values are planning illustrations based on the observed effect, not observed power. Observed power is not an informative substitute for reading the estimate, its interval, and the trial's design; these figures instead show how participant requirements would vary under the stated assumptions. The record does not report an original sample-size calculation to compare with this illustration.

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 = 0.033; treatment proportion p₁ = 0.260; average p̄ = 0.146.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5000 = 0.9799.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4735 = 0.3985.
4. n = (0.9799 + 0.3985)² / (0.2271)² = 36.8, 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 <- 0.0328638497652582                          # control proportion
p1 <- 0.26                          # 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(1290341)
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 = 56 (80% power), 74 (90% power)
 50% of observed effect: n per arm = 99 (80% power), 131 (90% power)
power.prop.test: 36.8 
Simulated power at n = 37 per arm: 0.864 (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 a sponsor analysis using the Cochran-Mantel-Haenszel method. It records a p-value of 0.001 and also lists p <0.025 for the superiority-or-other analysis. The registry does not give enough detail to resolve why both p-value entries appear or to reproduce the method's precise implementation. The sponsor's analysis should be distinguished from the unadjusted recalculation, which uses the posted group summaries and reports a risk difference, relative measures, intervals, and p <0.001.

The recalculated comparison is explicitly unadjusted. It should not be treated as a replacement for the sponsor's analysis, because the two methods may address the data differently. The registry record does not describe the Cochran-Mantel-Haenszel strata or other details needed to align the calculations. The sponsor's reported method and result are therefore the trial's own analysis as recorded, while the recalculation is a separate descriptive check based on posted summary statistics.

The discrepancy flag is false, so the record does not identify a discrepancy requiring a precedence statement. The numerical p-values nonetheless differ in presentation and method, and should be reported as recorded rather than collapsed into a single result. Both are consistent with a contrast that the registry characterizes as a superiority analysis, but neither p-value alone measures effect magnitude or resolves the limitations of the analysis population and missing-data reporting.

14. Multiplicity, Missing Data and Analysis Populations

The record lists two outcome measures and one analysis. The primary outcome is complete cure of interdigital tinea pedis at Week 6. One secondary outcome is listed: effective treatment and mycological cure of interdigital tinea pedis at Week 6. The registry does not describe a multiplicity adjustment, a hierarchy for testing outcomes, or how interpretation should account for testing more than one outcome. Those procedures are not reported in the registry record; their absence from the record is not evidence that no such procedures existed.

The population for the primary outcome is described as the Full Analysis Set: a subset of the Safety Evaluation Set with positive mycology 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 a portion of the study process described in an incomplete sentence. The full explanation is not reported in the registry record. The definition makes clear that availability of the primary variable is part of inclusion, but the record does not say how many outcomes were unavailable or why.

The registry does not report the missing-data method, imputation approach, sensitivity analyses, or a complete accounting of participants by outcome availability. It is therefore not possible from the record to assess whether missing outcome data could have changed the estimated comparison. In general, analyses that use only participants with available outcomes rely on assumptions about how missingness relates to outcome and group assignment; different assumptions can yield different estimates. This is a general concern, not a claim about the actual missingness mechanism in this trial.

The analysis is reported as Cochran-Mantel-Haenszel, but the registry does not identify the strata or provide full model details. It also does not report interim analyses, a complete statistical analysis plan, or a multiplicity strategy. These details matter when interpreting confirmatory claims because they clarify which comparisons were planned and how uncertainty was controlled. They cannot be inferred from the listed p-values or from the number of posted outcomes alone.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (0.3%), osteoarthritis (0.3%), urethral stenosis (0.2%).

The safety record lists serious adverse events for 572 participants at risk in the NAFT-600 group, with 1 serious adverse event, and 287 participants at risk in the placebo group, with 2 serious adverse events. These are the posted counts and their at-risk denominators. They are not the efficacy denominators used for complete cure, and the two sets of group sizes should not be conflated.

The record also lists appendicitis and osteoarthritis at 0.3% each and urethral stenosis at 0.2% among the top serious terms. It does not specify in this listing which treatment group each term occurred in, or provide enough detail to establish whether terms overlap with the group-level counts. The term list should therefore be read as a registry listing, not as a comparative safety analysis.

Deaths are not reported in the registry record. The serious-event counts alone do not establish whether an event was caused by treatment, and the listed counts should not be interpreted as a complete account of all safety outcomes. The record provides no inferential comparison for serious adverse events. Small counts can also make estimates of comparative risk imprecise; that is a general statistical consideration, not a conclusion about causation or clinical importance in this trial.

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

The posted primary outcome shows a higher observed complete-cure proportion in the NAFT-600 group than in the placebo group at Week 6: 26% compared with 3.3%. The result refers specifically to the registry's combined endpoint, which required negative dermatophyte culture and KOH results and absence of erythema, scaling, and pruritus. It is not a report of each component separately.

The unadjusted recalculation estimates the risk difference as 0.227, with an interval from 0.178 to 0.276. The sponsor-reported analysis uses the Cochran-Mantel-Haenszel method and records p-values of 0.001 and p <0.025. These statistics characterize the observed comparison under their respective methods; they do not answer every question about the trial. The record does not fully describe the sponsor method's strata, missing-data procedures, or multiplicity approach.

The outcome applies to the stated Full Analysis Set, not necessarily to every person enrolled. That set required membership in the Safety Evaluation Set, positive mycology culture at baseline, and an available primary efficacy variable. Because the registry does not fully explain unavailable outcomes, the effect of missing data cannot be assessed from the record alone. The results also concern a specific assessment at Week 6, after the described two-week topical treatment period; they do not establish how outcomes might differ at other time points.

These findings should not be extended automatically to other forms of tinea pedis, other populations, other treatment schedules, or outcomes not measured in the posted results. Nor do the endpoint statistics establish effects on outcomes beyond complete cure as defined, or determine the cause of adverse events. The results describe a randomized, double-blind comparison as recorded, but details of implementation and analysis remain incomplete. Statistical evidence, uncertainty, population definition, and limitations all contribute to interpretation; no single percentage or p-value provides the whole account.

17. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions matter. Complete cure was not simply a negative culture or an improvement in symptoms: it required both negative dermatophyte culture and KOH results and the absence of erythema, scaling, and pruritus. A reader can understand the reported proportion only by knowing which criteria participants had to meet. The result is specific to that composite definition and the Week 6 assessment.

It also shows why absolute and relative measures should be read together. The registry reports proportions of 26% and 3.3%, while the unadjusted recalculation expresses the contrast as a risk difference, risk ratio, and odds ratio. Each emphasizes a different scale. Reporting more than one measure can make the statistical contrast easier to interpret, provided the scales are not confused and the uncertainty around each is considered.

The record also offers a useful distinction between a trial's own analysis and a recalculation from summary results. The sponsor reports a Cochran-Mantel-Haenszel analysis; the unadjusted recalculation does not reproduce all details of that method. Those results can inform interpretation in different ways, but the registry does not provide enough information to reconstruct every analytic choice.

Finally, the trial underscores the importance of defining the analysis population and documenting missing-data handling. The Full Analysis Set excludes participants without an available primary efficacy variable by its stated definition, but the record does not fully explain missingness or sensitivity analyses. Even a clear separation in observed outcome proportions should be interpreted alongside these design and reporting details. This is a statistical lesson about reading clinical trial evidence, not a treatment recommendation.

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 a truncated description of the Full Analysis Set: it identifies the Safety Evaluation Set, positive baseline mycology culture, and availability of the primary efficacy variable, but the complete rationale and detail are not reported. The record also does not state how many participants lacked an available primary efficacy measure or how such missing outcomes were handled. This limits assessment of the influence of missing data on the posted comparison.

Although the analysis is named as Cochran-Mantel-Haenszel, the record does not report the strata or other implementation details. It lists p = 0.001 and p <0.025, without explaining their relationship. A separate unadjusted recalculation is available, but it cannot substitute for undocumented features of the sponsor's analysis. The registry does not provide the original sample-size justification, the full statistical analysis plan, interim analysis information, or a multiplicity strategy.

The primary result is a single endpoint at Visit 4/Week 6, defined using both mycology and clinical signs and symptoms. The record lists a secondary outcome but does not provide a full account of all planned outcomes or their testing order. Follow-up beyond the stated assessment is not reported in the record, so these results do not describe later outcomes.

The safety listing reports serious adverse event counts and selected serious terms, but does not provide a comparative statistical analysis or link the terms to treatment groups in the listing. Deaths are not reported in the registry record. Randomization and double masking are identified, but their practical procedures are not described. These gaps do not establish that a procedure was absent; they limit what can be verified from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Evaluation of the Efficacy and Safety of NAFT-600 in Subjects With Tinea Pedis — NCT01290341.
• Registry record last updated 2013-09-26; status last verified 2013-07.
• Results first posted 2013-09-26.
• 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

NCT01290341 is a completed Phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of NAFT-600 for tinea pedis. The registry lists enrollment as 860, a start of 2011-02, and primary completion of 2011-11. NAFT-600, identified as naftin 2 % gel, and topical placebo were each applied once daily for two weeks; the registry summary describes a 6-week study.

The primary outcome was complete cure of interdigital tinea pedis at Visit 4/Week 6. Posted proportions were 26% for NAFT-600 and 3.3% for placebo. The registry reports a Cochran-Mantel-Haenszel analysis, while the unadjusted recalculation gives a risk difference of 0.227 with an interval from 0.178 to 0.276. The primary population was a defined Full Analysis Set, and the registry does not fully report missing-data handling or several details of the analysis plan.