Safety and Efficacy Study of Subjects With Onychomycosis of the Great Toenail: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Subjects With Onychomycosis of the Great Toenail (NCT01278394), a na phase 2 study. The primary outcome is Clinical Evidence of Complete Clearance of the Treatment-targeted Great Toenail Plus a Negative Fungal Culture at Day 360.

2. Clinical Question

This question combines a clinical assessment with a laboratory assessment. A clear nail is defined in the endpoint description as a completely normal nail unit; the culture result must also be negative. Requiring both findings makes the endpoint more restrictive than either finding alone. It asks whether the clinical appearance and the fungal culture meet the stated criteria at the specified assessment time, rather than describing change from baseline by itself.

The record also names secondary outcomes involving clear nail growth, mycological evaluations, and time to clinical evaluation of clear or at least 5 mm of clear nail growth. Their outcome-specific results are not reported in the registry record. The primary question is therefore identifiable, but the posted information does not establish the proportion meeting it or the precision of any estimate.

3. Trial Design

The registry identifies NCT01278394 as a completed Phase 2 study sponsored by Pfizer. Its official title describes an open-label, rising multiple-dose, multicenter evaluation of topical AN2690 5.0% and 7.5% solution. The listed intervention and arm description identify AN2690 Solution, 5.0%, in a single-group model. The registry lists enrollment of 29.

Open-label means masking was not used; the masking field is NONE. The allocation field is NA, and the model is SINGLE GROUP. No comparator is listed. Consequently, the design does not provide a concurrent control group for separating treatment-associated change from the natural course of the condition, assessment variation, or other influences. It is not a like-for-like controlled comparison.

The study dates are listed as 2007-03 for start and 2008-07 for primary completion, and status is COMPLETED. Those registry dates do not establish the duration of each participant’s treatment or follow-up. The primary outcome timeframe is Day 360, but details about visit windows and participant-level follow-up are not reported in the registry record.

The rising multiple-dose wording in the title does not, by itself, specify how dose escalation was conducted or which participants received each concentration. Although the title names 7.5%, the arm description lists 5.0%; the dose-level assignment and any corresponding outcome data are not reported in the registry record. Randomization, dose sequence, treatment duration, adherence assessment, and protocol deviations are also not described in the available record.

The study is therefore best understood as a single-group assessment with a defined clinical and culture-based endpoint, rather than as an efficacy comparison between treatments. The design information establishes the broad structure but leaves important operational details and the primary numerical result unreported.

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: All subjects in Cohort 3 were treated with 5.0% AN2690 Solution.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy data were analyzed for the ITT population. For efficacy variables, the last observation was carried forward (LOCF) to impute missing observations.

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: All analyses were performed using the intent-to-treat (ITT) population.

6. Primary Endpoint

The registry lists the primary outcome as Clinical Evidence of Complete Clearance of the Treatment-targeted Great Toenail Plus a Negative Fungal Culture at Day 360, measured over Day 360.

The primary endpoint is the number or proportion of participants with clinical evidence of complete clearance of the treatment-targeted great toenail plus a negative fungal culture at Day 360. The endpoint description defines clinical clearance as a clear, completely normal nail unit and requires a negative culture from the targeted toenail. The stated unit is participants, and the stated parameter is NUMBER.

Combining clinical appearance and fungal culture gives the endpoint a joint criterion: both components must be met. Clinical assessment describes the visible nail condition, while the culture result is a mycological assessment. Together, they distinguish complete clearance under the registry’s definition from an outcome that meets only one component. This is why a combined endpoint can be useful when a study seeks to characterize both clinical and mycological status.

The assessment is fixed at Day 360. A result at that time would describe the participants meeting the criteria at that assessment, under the registry’s analysis approach. It would not, by itself, describe when clearance occurred, whether it persisted at other times, or how the outcome compares with an untreated or alternative-treatment group.

The registry says efficacy variables used the ITT population and LOCF to impute missing observations. The observed endpoint count or proportion, its uncertainty, and any statistical test are not reported in the registry record. Thus, the endpoint’s definition is available, but its estimated frequency and precision cannot be interpreted from the recorded outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information identifies the endpoint, analysis population, and missing-data approach, but does not describe a full analysis plan. In particular, the record does not report the primary endpoint estimate, an interval estimate, a hypothesis test, or covariate adjustment. The absence of these details means the outcome cannot be reconstructed from the registry description.

What does a proportion describe?

For a binary endpoint, each participant is classified according to whether the endpoint criterion is met. A proportion expresses the number meeting the criterion relative to the relevant analysis population. Here, the criterion is joint: clinical evidence of a clear, completely normal nail unit and a negative fungal culture from the targeted toenail at Day 360. The registry states that the unit is participants and that efficacy analyses used the ITT population, but the result and the analysis denominator are not reported in the registry record.

A proportion is a descriptive estimate for the participants included in an analysis. It is not automatically a treatment effect. In a single-group study, there is no concurrent comparator proportion from which to form a randomized treatment contrast. Any claim about what would have happened under another treatment or without treatment would require evidence beyond this single-group endpoint result.

What would a confidence interval add?

In general, a confidence interval communicates the uncertainty around an estimate under specified statistical assumptions. For a proportion, it reflects that the observed participants are only a sample of the population of interest and that different samples could produce different estimates. An interval is not a guarantee that the true value lies within its limits, nor does it correct bias from study design, measurement, or missing data. No confidence interval is reported for the primary endpoint in the registry record, so its statistical precision cannot be assessed.

What is the role of the analysis population?

The registry states that efficacy data were analyzed for the ITT population. An analysis population defines which participants contribute to the analysis and can affect both the estimate and its interpretation. The record does not define membership in the ITT population, explain whether any participants were excluded from a particular efficacy analysis, or describe how participant eligibility for the Day 360 assessment was determined. The term alone is not enough to reconstruct the denominator.

How does LOCF work, and what are its limits?

Last observation carried forward uses a participant’s last available observation as the value for a later assessment that is missing. The registry says LOCF was used to impute missing observations for efficacy variables. This procedure produces an analysis value where a later measurement is absent, but it relies on an assumption that carrying the previous value forward is a reasonable representation of the missing value. That assumption may not hold if the outcome changes after the last observed assessment.

LOCF can make results sensitive to the timing and reasons for missing observations. Missingness related to worsening, improvement, tolerability, or logistics can have different implications. The registry does not report how many observations were imputed, when they were last observed, why values were missing, or whether alternative missing-data analyses were conducted. It is therefore not possible to judge the impact of LOCF on the endpoint estimate.

Why does a single-group design matter statistically?

A single-group analysis can estimate the outcome observed within the study group, subject to measurement and missing-data assumptions. It cannot provide a randomized between-group estimate because there is no listed comparator. The open-label status may also matter for outcomes involving clinical judgment, although the record does not report how assessments were standardized or whether assessors were independent. These limitations concern interpretation; they do not change the endpoint definition.

The registry’s sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Such illustrations are planning scenarios, not observed trial outcomes and not observed power. They are not evidence that this single-group study was designed with those assumptions. A trial-specific sample-size justification is not reported in the registry record.

Over-dispersion is a general concern when outcome variation exceeds what a simple statistical model assumes. It can make standard errors too small if the model does not account for the extra variation. Whether over-dispersion is relevant depends on the outcome and analysis model. The registry does not report a model for the primary endpoint, so no claim can be made about whether over-dispersion was assessed or addressed.

Likewise, the registry does not report a statistical method for the time-to-clinical-evaluation secondary outcome. In general, time-to-event methods must address censoring, which occurs when the event time is not observed for a participant during the relevant observation period. The outcome title alone does not establish how such observations were handled or whether a time-to-event analysis was performed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, including the primary endpoint and secondary outcomes concerning clear nail growth, mycological evaluations, and time to clinical evaluation of clear or at least 5 mm of clear nail growth. It does not report a multiplicity plan, such as a prespecified ordering of hypotheses or an adjustment for assessing multiple outcomes. The statistical approach to repeated mycological evaluations is also not reported in the registry record.

Multiplicity matters when several outcomes or repeated assessments are examined. In general, the more statistical questions considered, the greater the chance that an apparently notable result could arise by chance if each is judged separately. Methods for addressing this depend on whether outcomes are confirmatory or exploratory and on how the analyses were planned. The registry record does not say how these issues were handled, so no adjustment or hierarchy should be assumed.

For missing data, the stated approach is LOCF for missing efficacy observations. The record does not quantify missingness, distinguish missing endpoint components, describe reasons for missing assessments, or report sensitivity analyses. Those omissions matter because the imputation assumption can influence the estimated proportion meeting the joint endpoint.

Efficacy analyses are described as using the ITT population, but the population’s operational definition is not reported. The registry also does not give outcome-specific denominators or detailed analysis results. A count of 0 analyses is recorded; statistical estimates and inferential procedures are therefore not reported in the registry record. The stated population and imputation method do not fill those gaps.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: uterine haemorrhage (unrelated) (3.4%).

The safety record lists 29 participants at risk for serious adverse events and 1 with a serious adverse event. It also lists 29 at risk for other adverse events and 16 affected. These are counts recorded for the AN2690 Solution, 5.0% group. The registry lists uterine haemorrhage as the top serious adverse-event term, labels it unrelated, and gives 3.4%.

These figures describe reported events in a single-group study. They do not compare event frequency with another treatment or with a control group, and they do not establish that treatment caused or prevented an event. The unrelated designation is the registry’s recorded relationship assessment for the listed term; the basis for that assessment is not reported in the registry record.

Counts alone do not convey event timing, duration, recurrence, severity beyond the serious classification, or the number of events per affected participant. The registry record does not provide those details. The reported serious and other adverse-event counts should therefore be read as descriptive safety information, not as a comparative risk estimate.

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

The study’s primary question is clearly defined: whether participants had both a clinically clear treatment-targeted great toenail and a negative fungal culture at Day 360. The registry also identifies the intended population, intervention arm, single-group design, analysis population, and LOCF approach. These details establish what the study set out to assess and how missing efficacy observations were handled.

However, the primary endpoint result is not reported in the registry record. There is no posted number of participants meeting the endpoint, no proportion, and no estimate of precision. The study’s enrollment of 29 cannot substitute for those outcome data. Without the result and its denominator, the frequency of complete clearance under the registry definition cannot be described.

Even a reported single-group proportion would not answer how outcomes compare with another treatment or with no treatment. No comparator is listed, allocation is NA, and masking is NONE. Any observed outcome would be descriptive of this study group and would not, on its own, isolate the effect of the intervention from other explanations.

The safety counts provide information about events recorded in the group, but they do not establish comparative safety or causation. The record’s unrelated designation for uterine haemorrhage should be reported as recorded, without treating it as proof that the event could not be associated with treatment.

Accordingly, the registry record supports a careful account of the study design and the outcome definitions, but not a conclusion about the magnitude, precision, or comparative meaning of the primary efficacy result. It also does not permit a complete assessment of missing-data sensitivity, multiplicity, or the detailed safety profile.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly named endpoint and an available endpoint result are both necessary for statistical interpretation. The primary outcome specifies a joint clinical and mycological criterion at Day 360. That definition makes the target of measurement explicit, but without the observed count or proportion, readers cannot assess how frequently participants met the criterion or how precisely it was estimated.

It also highlights the distinction between describing an outcome and estimating a comparative effect. A single-group design can document outcomes in the enrolled group, but no comparator is listed to provide a controlled contrast. The open-label design and lack of masking are relevant context, particularly because one endpoint component is a clinical assessment. The registry does not report whether other procedures were used to limit assessment variation.

The LOCF statement is another important statistical detail. Naming an imputation method does not establish that missing data had little influence; understanding that influence requires information about missingness and appropriate sensitivity analyses. Those details are not reported in the registry record.

Finally, safety counts and a listed adverse-event term need careful framing. Counts in a single group are descriptive rather than comparative, and a recorded relationship designation is not a substitute for event-level context. Taken together, these features show how design, endpoint definition, missing-data handling, and completeness of reporting shape what can be concluded from a clinical trial record.

14. 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 principal limitation for interpreting efficacy is that the Day 360 primary result is not reported in the registry record. Without the endpoint count or proportion and an uncertainty estimate, neither the observed frequency nor its precision can be assessed. Secondary outcome results are also not reported.

The study is single-group, with no comparator listed, allocation recorded as NA, and masking recorded as none. This structure does not support a randomized treatment contrast, and open-label assessment may be relevant to the clinical component of the endpoint. The registry does not describe assessment procedures that might clarify how clinical judgments were standardized.

The enrollment is 29, but the record does not provide the outcome-specific denominator, missingness pattern, or ITT membership definition. LOCF is stated for missing efficacy observations, while the extent and consequences of imputation are not reported. No sensitivity analyses are described.

The official title names 5.0% and 7.5% solutions and a rising multiple-dose design, whereas the listed arm identifies AN2690 Solution, 5.0%. Dose-level assignment and outcome data for any other concentration are not reported in the registry record. The record also does not provide a detailed treatment schedule, visit windows, or participant-level follow-up information.

Multiplicity handling, the trial-specific sample-size justification, statistical tests, confidence intervals, and detailed analysis specifications are not reported in the registry record. Safety information is limited to the recorded counts and listed serious-event term; timing and event-level details are not reported.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Subjects With Onychomycosis of the Great Toenail — NCT01278394.
• Registry record last updated 2018-12-06; status last verified 2018-11.
• Results first posted 2014-08-15.
• 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.

18. Record Summary

NCT01278394 is a completed Phase 2, open-label, single-group study sponsored by Pfizer. The registry lists enrollment of 29 and AN2690 Solution, 5.0%, as the intervention. The official title describes a rising multiple-dose, multicenter study and names 5.0% and 7.5% solutions; details of dose assignment are not reported in the registry record.

The primary endpoint is clinical evidence of complete clearance of the treatment-targeted great toenail plus a negative fungal culture at Day 360. Efficacy analyses are described as using the ITT population, with LOCF for missing observations. The endpoint result, statistical estimates, and detailed analysis plan are not reported in the registry record.

The safety record lists 1 serious adverse event among 29 at risk and 16 with other adverse events among 29 at risk. Uterine haemorrhage is listed as unrelated with a reported 3.4%. With no comparator listed, the safety figures are descriptive rather than comparative.