Safety and Efficacy of NVXT Solution in Mild-to-Moderate Fungal Infection of the Toe Nail: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of NVXT Solution in Mild-to-Moderate Fungal Infection of the Toe Nail (NCT02343627), a randomized phase 2 study. The primary outcome is Number of Participants With Negative Fungal Culture.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, parallel-arm, phase 2 pilot study comparing NVXT Solution with the vehicle of the test product. The official title characterizes the study as placebo-controlled and focused on safety and efficacy. Sun Pharmaceutical Industries, Inc. is listed as the sponsor. The registry lists an enrollment of 47 and a completed status.

The registry dates the study start to 2014-12 and primary completion to 2016-01. The NVXT arm description specifies once-daily treatment for 60 days; the vehicle arm has the same once-daily, 60-day schedule. The primary endpoint is described separately as the number of participants with negative fungal culture after repeated once-daily topical applications for 28 days. The registry record does not explain how the stated 28-day endpoint relates to the 60-day intervention descriptions.

For the primary endpoint, the posted comparison includes 33 participants in the NVXT Solution arm and 12 in the vehicle arm. These are the endpoint counts reported for the comparison, not a description of every enrolled participant or of the safety population. The registry record does not report the allocation ratio, the method used to generate the randomization sequence, allocation concealment, stratification, or reasons for the difference between the endpoint and safety denominators. It also does not report the original sample-size rationale or the trial’s detailed statistical analysis plan.

The pilot design and the limited posted endpoint information make this a study to read as an initial comparison, not as a definitive estimate. The registry record lists one outcome measure and no secondary outcome results. Details about participant characteristics, eligibility criteria beyond mild-to-moderate toe-nail fungal infection, and the timing of all study visits 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

Analysis population for the primary outcome, as defined in the registry: Subjects with fungal culture collected at the study day 28 visit. The subjects may not complete all study visits.

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 Number of Participants With Negative Fungal Culture, measured over 28 days.

The primary endpoint counts participants with a negative fungal culture. A fungal culture is a laboratory assessment of whether fungus grows from the collected specimen; a negative result is the endpoint state counted in this outcome. The registry describes the endpoint as the number of participants with negative fungal culture after repeated once-daily topical applications. Its timeframe is 28 days, and the endpoint population is subjects with a fungal culture collected at the study day 28 visit. The description notes that these subjects may not complete all study visits.

This is a binary outcome at the participant level: each participant contributes a result categorized as negative or not negative for the reported count. Binary outcomes are useful when the research question concerns whether a defined event or state occurred, rather than the degree of change on a continuous scale. Counting participants with a negative culture gives a direct description of how often that endpoint was observed in each arm.

The measure does not, by itself, describe symptom change, the extent of nail involvement, persistence of a culture result, or outcomes at later follow-up. Those outcomes are not reported in the registry record. The registry also describes treatment for 60 days in both arms, whereas the primary endpoint timeframe is 28 days; the relationship between those time references is not explained. Therefore, interpretation should stay tied to the posted culture result and its stated endpoint population rather than assuming a different assessment schedule or a broader measure of clinical response.

7. Results Posted in the Registry

• NVXT Solution: 42.4% (14/33) versus 16.7% (2/12) on control; risk difference 25.8 percentage points (95% CI -1.2 to 52.8), risk ratio 2.55 (0.68–9.59); unadjusted two-proportion z-test p = 0.110.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry posts a participant count for a binary endpoint and a comparison between NVXT Solution and the vehicle. The following descriptions explain the statistical quantities in general terms and then relate them to the posted results.

What does a binary endpoint represent?

In general, a binary outcome classifies each participant into one of two categories for a specified endpoint, such as whether a particular event occurred. Here, the counted category is a negative fungal culture. The arm-level counts are 14 participants with a negative culture among 33 in the NVXT arm, and 2 among 12 in the vehicle arm. The corresponding posted event proportions are 0.424 and 0.167. A count and its denominator should be considered together: the count alone does not indicate how common the endpoint was in the arm.

The registry identifies the primary result as a count of participants, not a continuous measurement or a time-to-event outcome. It does not report a distribution of culture values or a time until culture became negative. Analyses appropriate for other outcome types cannot be assumed to have been used.

What does the risk difference describe?

In general, a risk difference compares event proportions by subtracting one arm’s proportion from the other. It is expressed on the proportion scale, so zero indicates equal proportions and a positive or negative value indicates the direction of the contrast according to the arm ordering. The posted risk difference is 0.258, with a confidence interval from -0.012 to 0.528. The ordering in this comparison is NVXT Solution relative to the vehicle. The point estimate is positive, but its interval includes zero, so the estimate is imprecise about the direction and size of the difference.

How do relative measures differ?

In general, a risk ratio compares the event proportions as a ratio, while an odds ratio compares the odds of the event between arms. A value of 1 on either ratio scale represents no relative difference. The posted risk ratio is 2.545, with a confidence interval from 0.676 to 9.587. The posted odds ratio is 3.684, with a confidence interval from 0.695 to 19.53. Both intervals include 1 and span a wide range of possible relative effects. Odds and risks are different quantities, especially when an outcome is not rare, so their numerical values should not be treated as interchangeable.

What does a confidence interval communicate?

In general, a confidence interval describes the uncertainty around an estimate under a statistical procedure and its assumptions. It is not a guarantee that the true effect lies within the reported limits, nor is it a range containing a specified probability that the effect takes any particular value. A wider interval indicates less precision than a narrower interval on the same scale. For this result, the risk-difference interval extends from a small negative value to a substantially positive value, showing that the observed comparison does not pin down the effect closely.

How should the p-value be read?

In general, a p-value measures how compatible the data are with a specified null model, using a test statistic and its assumptions. The posted unadjusted p-value is 0.11. It is not the probability that the null hypothesis is correct, and it does not tell how large or clinically important an effect is. A p-value also does not replace the estimated effect and its interval: those convey direction, scale, and precision. The registry record does not report the test procedure, whether any adjustment was planned, or the complete statistical analysis plan, so details beyond the posted unadjusted result are not available.

What information about the analysis is missing?

The registry reports zero posted analysis entries. It does not report a model specification, covariate adjustment, method for handling missing culture results, or a detailed definition of the analysis population beyond the endpoint description. The posted comparison is therefore best described using the counts, estimates, intervals, and unadjusted p-value recorded for this endpoint. It should not be characterized as adjusted for baseline differences or as an intention-to-treat analysis, because those details are not reported in the registry record.

These general concepts help distinguish the observed estimate from the uncertainty around it. The counts describe what was observed among participants with reported endpoint data; the risk difference and ratio measures describe the comparison on different scales; and the intervals and p-value summarize uncertainty under statistical procedures. None resolves the missing details about participant flow, endpoint availability, or the original analysis plan.

10. Confidence Intervals and Precision

The primary comparison has limited precision. The risk-difference estimate is 0.258, and its confidence interval runs from -0.012 to 0.528. Because zero lies inside this interval, the posted data do not sharply distinguish a positive difference from no difference or a small difference in the opposite direction. The broad span also allows substantially different magnitudes of contrast, so the point estimate should not be treated as a precise measure of the underlying effect.

The relative-effect intervals tell a similar story. The risk ratio is 2.545, with an interval from 0.676 to 9.587; the odds ratio is 3.684, with an interval from 0.695 to 19.53. Each interval includes 1, which represents no relative difference, and each extends across a wide range. The ratio estimates therefore do not give a tightly determined relative effect either.

In general, precision is influenced by the amount of endpoint information and by variability in the data. The primary comparison is based on 33 participants in the NVXT arm and 12 in the vehicle arm. Those denominators, together with the observed counts, are relevant context for the breadth of the intervals. The record does not report a precision target or the original sample-size justification, so it is not possible to say whether the uncertainty met the study’s initial design aims.

The p-value of 0.11 is consistent with the interval’s uncertainty, but it should not be read as a measure of precision on its own. The confidence intervals make the range of compatible effects more visible. Overall, the observed direction is positive on the risk-difference scale, but the posted intervals leave considerable uncertainty about both direction and magnitude.

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 event counts. They illustrate the number of participants per arm associated with specified power targets under stated assumptions. The 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 a stated fraction of the observed effect: 100%, 75%, or 50%. The registry record does not report the trial’s own original sample-size assumptions or justification.

The 80% power column means that, under the planning assumptions and for the effect size used in that row, the calculation targets an 80% chance of detecting that effect using the specified test procedure. The 90% power column expresses the corresponding target at 90%. These are planning concepts, not guarantees about a future study’s result. For 100% of the observed effect, the figures are 49 participants per arm for 80% power and 64 participants per arm for 90% power. For 75% of the observed effect, they are 81 and 108 participants per arm. For 50% of the observed effect, they are 167 and 224 participants per arm.

Smaller effects require more participants to reach the same target power under these assumptions, because weaker differences are harder to distinguish from random variation. The sequence is an illustration based on the observed effect, not a reconstruction of the original design. This is not observed power.

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 = 0.167; treatment proportion p₁ = 0.424; average p̄ = 0.295.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6452 = 1.2646.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6190 = 0.5210.
4. n = (1.2646 + 0.5210)² / (0.2576)² = 48.1, rounded up to 49 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 <- 0.166666666666667                          # control proportion
p1 <- 0.424242424242424                          # 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(2343627)
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 = 49 (80% power), 64 (90% power)
 75% of observed effect: n per arm = 81 (80% power), 108 (90% power)
 50% of observed effect: n per arm = 167 (80% power), 224 (90% power)
power.prop.test: 48.1 
Simulated power at n = 49 per arm: 0.810 (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 lists one outcome measure and no posted secondary outcome results. It also lists zero analysis entries. The primary endpoint is the number of participants with a negative fungal culture at the stated 28-day timeframe. This record does not establish whether other outcomes were measured but not posted, whether multiple versions of an endpoint were examined, or whether additional analyses were performed outside the registry record.

Multiplicity concerns arise when several outcomes, timepoints, comparisons, or analysis choices are tested. In general, considering many tests can increase the chance of at least one apparently unusual result if no adjustment or prespecified hierarchy is used. Whether that issue arose in this study cannot be determined from the posted record: a multiplicity strategy, outcome hierarchy, and complete list of planned analyses are not reported in the registry record. The p-value is explicitly unadjusted, and no adjusted result is posted.

Missing data are also relevant. The endpoint population is described as participants with fungal culture collected at the study day 28 visit, and the registry notes that these participants may not complete all study visits. The primary comparison reports 33 participants in the NVXT arm and 12 in the vehicle arm, while the safety figures use different at-risk counts. The record does not explain why denominators differ, how many endpoint results were unavailable, or whether missing culture results were excluded, imputed, or handled by another method. No missing-data sensitivity analysis is reported.

The registry does not specify whether the primary analysis followed an intention-to-treat principle, a per-protocol definition, or another population rule. It does not report exclusions, deviations from the assigned intervention, or an analysis plan for participants without a day 28 culture. Consequently, the posted count comparison can be described as reported, but its relationship to all randomized participants cannot be fully assessed.

These omissions do not prove that multiplicity or missing-data methods were absent from the study; they mean the methods are not reported in the registry record. That distinction matters when assessing how securely the posted estimate represents the planned primary analysis.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse event figures report zero serious adverse events among 35 participants at risk in the NVXT Solution group and zero among 12 participants at risk in the vehicle group. These are safety counts and denominators; they differ from the primary endpoint denominators, and the registry record does not explain the difference. Deaths are not reported in the registry record.

The registry also reports other adverse events affecting 7 participants at risk in the NVXT group and 3 in the vehicle group. These are listed separately from serious adverse events. The record does not provide event terms for the serious adverse event category, and the listed serious-event terms are empty. It does not give the nature, severity, timing, or duration of the other adverse events in the information available for this summary.

Zero reported serious adverse events in these groups means that none were recorded in the posted serious-event counts; it does not establish that serious events are impossible or rule out uncommon harms. Safety interpretation depends on the size and duration of observation, event definitions, completeness of reporting, and the population assessed. Those details are not all reported in the registry record. The posted figures should therefore be read as descriptive counts, not as a complete characterization of safety.

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

The posted results describe a pilot comparison of negative fungal culture between NVXT Solution and its vehicle. The observed counts are 14 of 33 participants in the NVXT arm and 2 of 12 in the vehicle arm. The risk-difference estimate is 0.258, but its confidence interval extends from -0.012 to 0.528. The ratio-based intervals are also wide and include their respective no-difference values. These findings describe the observed endpoint and the uncertainty in its comparison; they do not establish a precise treatment effect.

The result does not show that every participant responded, nor does it establish what happened to participants without an endpoint culture. The endpoint population is limited to people with a culture collected at the study day 28 visit, and the record says they may not complete all visits. Handling of unavailable cultures is not reported in the registry record. The relationship between the day 28 endpoint and the 60-day treatment descriptions is also not explained.

The result is specific to the registry’s culture endpoint. It does not by itself describe symptoms, nail appearance, recurrence, longer-term outcomes, or other measures not reported in the registry record. The posted safety information is likewise limited to event counts and at-risk denominators; it is not a full account of event types or duration.

Because this is a pilot with limited endpoint counts and broad intervals, the estimate remains uncertain. The unadjusted p-value of 0.11 does not establish whether the treatment groups are equivalent, and it is not a probability that either treatment is effective. The registry record does not report a detailed analysis plan, missing-data methods, multiplicity strategy, or original sample-size rationale. The defensible interpretation is therefore narrow: the observed negative-culture counts favored the NVXT arm in this comparison, while the precision and reporting limitations prevent a firm conclusion about the size or reliability of the difference.

16. Why This Trial Matters Statistically

This study illustrates why a point estimate should be read alongside its uncertainty. The observed risk difference is positive, but the confidence interval extends across zero and covers a broad range. Reporting only the direction or the point estimate would leave out the central statistical feature of the result: the data do not estimate the comparison precisely. The risk-ratio and odds-ratio intervals likewise show that plausible relative contrasts span substantially different values.

It also demonstrates the importance of keeping endpoint counts, safety denominators, and enrollment distinct. The registry lists enrollment of 47, the primary comparison uses 33 participants in one arm and 12 in the other, and the safety assessment uses its own at-risk counts. These are different reported quantities, and the record does not explain their relationship. Treating them as interchangeable could obscure who contributed to each analysis.

The endpoint timing is another statistical consideration. The intervention descriptions specify 60 days of once-daily use, while the primary outcome description refers to a day 28 culture. Without an explanation of that relationship, readers should avoid assuming that the endpoint represents the end of the stated treatment course or a later follow-up outcome.

Finally, the absence of posted secondary results and analysis entries limits assessment of outcome selection, multiplicity, missing data, and the planned analysis population. These are not merely technical details: they affect how the reported comparison can be interpreted. The study is useful as an example of a randomized pilot with a clearly stated binary endpoint but incomplete registry detail about analysis and participant flow. The key statistical lesson is to separate what was observed from what remains uncertain or unreported.

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.

Several features of this specific record constrain interpretation. First, the trial is described as a pilot and the primary endpoint comparison uses 33 participants in the NVXT Solution arm and 12 in the vehicle arm. The confidence intervals are broad, so the effect estimate is not precise. The registry lists enrollment of 47, but it does not explain how enrollment relates to the endpoint denominators or why the arm counts differ.

Second, the timing descriptions do not align transparently: both interventions are specified as once daily for 60 days, while the primary endpoint is a fungal culture at day 28. The record does not explain whether the culture was collected during treatment, after a separate treatment period, or in another schedule. No alternative timing should be assumed.

Third, the endpoint population includes subjects with a culture collected at the day 28 visit and may exclude people who did not have that culture or did not complete other visits. The registry does not report missing endpoint counts, reasons for missingness, imputation, sensitivity analyses, or a definitive analysis population. As a result, the influence of incomplete endpoint data cannot be assessed.

Fourth, there is one posted outcome measure, no posted secondary outcome results, and no analysis entries. The detailed statistical plan, multiplicity approach, randomization procedures, allocation ratio, participant characteristics, and original sample-size justification are not reported in the registry record. These gaps prevent a full assessment of prespecification and comparability. Finally, safety reporting is limited to the serious and other adverse-event counts, at-risk denominators, and the absence of listed serious-event terms; deaths are not reported in the registry record. The posted information does not provide a comprehensive account of safety events.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Safety and Efficacy of NVXT Solution in Mild-to-Moderate Fungal Infection of the Toe Nail — NCT02343627.
• Registry record last updated 2018-09-19; status last verified 2018-08.
• Results first posted 2018-08-22.
• 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

The completed study, NCT02343627, is a randomized, double-blind, parallel-arm, phase 2 pilot study sponsored by Sun Pharmaceutical Industries, Inc. It compares NVXT Solution with the vehicle of the test product in mild-to-moderate fungal infection of the toe nail. The registry lists enrollment of 47, a start date of 2014-12, and primary completion in 2016-01.

The primary outcome is the number of participants with a negative fungal culture at the stated 28-day timeframe. The posted counts are 14 of 33 in the NVXT arm and 2 of 12 in the vehicle arm. The risk-difference estimate is 0.258, with a confidence interval from -0.012 to 0.528 and an unadjusted p-value of 0.11. The interval indicates substantial uncertainty around the comparison.

The registry describes once-daily treatment for 60 days in both arms but does not explain its relationship to the day 28 endpoint. It does not report the detailed statistical plan, missing-data methods, original sample-size rationale, or reasons for the endpoint and safety denominator differences. Safety figures and planning illustrations require separate interpretation from the primary endpoint result.