Nu-3 Topical Gel for Treatment of Diabetic Foot Ulcer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nu-3 Topical Gel for Treatment of Diabetic Foot Ulcer (NCT05276401), a randomized phase 2 study. The primary outcome is To Assess the Number of Participants With Treatment-related Adverse Events After Nu-3 Gel Use on cDFU as Assessed by CTCAE v4.0.

2. Clinical Question

3. Trial Design

The study was a phase 2a, randomized, placebo-controlled trial of topical bisphosphocin Nu-3 gel for clinically noninfected chronic diabetic foot ulcers. Its official title describes a multi-center, double-blind, dose-escalating study focused on safety and tolerability. The registry metadata identifies the masking as quadruple and the model as sequential. The relationship between the title's description of double-blinding and the metadata's quadruple masking is not explained in the registry record.

The listed interventions were 5% bisphosphocin topical gel, 10% bisphosphocin topical gel, and placebo topical gel. The arm descriptions group the two active doses under Active and describe both active and placebo gel as being applied twice daily for 28 days. Participant counts are listed as 2 in the active group and 1 in the placebo group. Separate counts for each active dose are not reported, so the arm-level outcome does not permit a dose-specific interpretation.

The registry lists enrollment of 3 and a terminated study status. The recorded study start was 2022-03-11, and primary completion was 2022-05-18. The reason for termination is not reported in the registry record. Although the study is described as randomized, the method used to generate or conceal allocation is not reported. Details about recruitment sites, treatment adherence, follow-up beyond the primary outcome timeframe, and protocol deviations are also not reported.

The stated primary focus was safety and tolerability, rather than a clinical efficacy outcome. The primary outcome was the number of participants with treatment-related adverse events over 28 days. The registry record lists one outcome measure and no posted analysis entries. It does not report a detailed statistical analysis plan, a sample-size justification, or how the dose-escalation model was implemented.

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

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 To Assess the Number of Participants With Treatment-related Adverse Events After Nu-3 Gel Use on cDFU as Assessed by CTCAE v4.0, measured over 28 days.

The primary endpoint counts participants with treatment-related adverse events after use of Nu-3 gel on chronic diabetic foot ulcers. The registry describes the events as treatment-emergent events related to the clinical investigational product and specifies assessment using CTCAE v4.0. The stated timeframe is 28 days. The endpoint is a participant count: it records whether participants experienced the specified event, rather than the total number of event episodes or a measure of ulcer healing.

Safety and tolerability outcomes are used in early clinical research to describe adverse events observed during treatment and to inform the assessment of a study intervention. A participant count can communicate how many people in each arm had an event, but it does not by itself show event severity, duration, recurrence, or the certainty of a difference between groups. Those aspects require additional event-level or statistical information.

The posted primary outcome lists 2 participants in the active group and 1 in the placebo group. The registry also reports serious and other adverse-event summaries, but the primary endpoint should not be treated as interchangeable with every adverse-event category. The record does not provide event descriptions for the primary outcome, nor does it report a dose-specific primary outcome. It therefore supports a limited account of the recorded counts over the stated timeframe, not a broader conclusion about safety or clinical benefit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either meets the endpoint definition during the stated timeframe or does not. The registry expresses the result as a count of participants with treatment-related adverse events. This is distinct from a count of all event episodes, because one participant may experience more than one event. The record does not say whether the outcome count represents participants with at least one qualifying event or provide event-level details, although the endpoint title describes a number of participants.

What does a participant count tell us?

A count is a direct descriptive summary of the participants recorded as having an event. Interpreting that count alongside the number of participants in the group gives context, but a count alone does not quantify an event rate or a treatment effect. The registry posts 2 participants in the active group and 1 in the placebo group, with group sizes of 2 and 1 respectively. With such limited group sizes, each participant's outcome has substantial influence on the group summary. These counts should not be read as a precise estimate for a wider population.

Comparative analyses for binary outcomes can use methods that estimate a difference in event proportions, a relative measure, or an odds-based measure. The choice depends on the design, event frequency, and analysis plan. Each method requires a defined estimand and an approach to uncertainty. The registry record does not post an estimated effect, confidence interval, or p-value. It explicitly indicates that a two-arm comparison is missing or not estimable, so a numerical comparative effect cannot be interpreted from the posted results.

Why does uncertainty matter?

In general, a confidence interval describes a range of values compatible with the observed data under a statistical model and a specified confidence procedure. A narrow interval indicates greater precision than a wide interval, while an interval spanning effects in different directions may leave the comparative result uncertain. These are general interpretations; the registry record does not provide a confidence interval for this outcome. It would be inappropriate to infer precision from the counts alone or to substitute an independently calculated interval for an analysis that is not posted.

Similarly, a p-value is a measure tied to a particular statistical test and its assumptions. It does not measure the probability that a treatment works, and its interpretation depends on the study design and analysis plan. No primary-comparison p-value or test is reported. The record also does not describe whether any statistical test was planned, what assumptions it would use, or how a small-sample analysis would be handled.

How should the dose groups be understood?

The interventions list 5% and 10% active gel, while the reported outcome arms use a combined Active label and a Placebo label. Thus, the posted primary count is not a comparison of each dose against placebo. A dose-escalation design can be organized to evaluate successive dose levels, but the detailed sequence, escalation criteria, and allocation of participants across dose levels are not reported in the registry record. No dose-specific estimate can be reconstructed from the arm-level outcome.

Randomization is intended, in general, to reduce systematic differences between treatment groups by allocating participants through a chance-based process. It does not guarantee balance in every characteristic, especially in a small study. The record identifies the study as randomized but does not report the randomization procedure, allocation concealment, or baseline characteristics. It therefore does not allow readers to assess group comparability or the implementation of randomization in detail.

Masking can, in general, reduce the influence of treatment knowledge on participant reporting, clinical care, and outcome assessment. The registry metadata identifies quadruple masking, while the official title describes a double-blind study. The record does not explain this difference or specify which roles were masked. No conclusion about the practical success of masking can be drawn from the information reported.

What do the planning illustrations mean?

Sample-size planning asks how many participants would be needed, under stated assumptions, to detect an effect with a chosen statistical procedure and level of power. Such calculations are prospective illustrations, not evidence that a study had that power or that its observed result is reliable. In this record, a two-arm planning comparison for the binary endpoint is marked as missing or not estimable. The registry does not report the trial's own sample-size justification or planned detectable effect. No planning estimate should be treated as a property of the observed study.

More generally, a planning calculation based on an observed effect can be especially unstable when the observed data come from a very small group. It can also be misleading if the observed effect is not a reliable estimate of the effect expected in a future study. The record describes planning assumptions for illustrative calculations, but it does not provide an estimable two-arm comparison for this endpoint. These planning concepts do not create additional evidence about the outcome.

Finally, analysis populations matter. A report should state which participants were included in each outcome analysis and how missing outcomes, treatment discontinuation, or protocol deviations were handled. Those details are not reported in the registry record. Without them, the posted counts cannot be linked to a clearly specified analysis population beyond the arm labels and participant counts listed.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Active", "Placebo")
n      <- c(2, 1)
events <- c(2, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Active  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  Placebo  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no posted analysis entries. It does not report a statistical analysis plan, any planned secondary or exploratory comparisons, or a method for controlling multiplicity. Multiplicity arises when several outcomes, treatment comparisons, timepoints, or statistical tests are considered; repeated testing can increase the chance of an apparently notable result arising by chance. This is a general concern, not evidence that such testing occurred in this study. The available record does not permit assessment of any multiplicity procedure.

The registry reports no posted secondary outcomes. It does not describe missing outcome data, participant withdrawals, exclusions, or the handling of participants who did not complete treatment or follow-up. It also does not identify an intention-to-treat, per-protocol, safety, or other analysis population. The posted group counts should therefore be understood only as registry-reported summaries, without assuming a particular population definition or missing-data method.

Randomization and masking are reported in the record, but procedural detail is limited. The record does not describe the allocation sequence, concealment, the identities of masked roles, or how unmasking was handled. It also does not clarify the relationship between quadruple masking in the registry metadata and double-blinding in the official title.

These omissions limit evaluation of how the primary outcome was analyzed and how robust the result may be to missingness, exclusions, or selective reporting. They do not demonstrate that a particular problem occurred; they mean that the relevant methods are not reported in the registry record.

12. Safety Results

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

Deaths

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 adverse-event summary lists serious adverse events affecting 0 participants in the active group and 0 in the placebo group. It lists deaths as 0 in both groups. The number of participants at risk is listed as 2 for active and 1 for placebo. These are the serious-event and death figures recorded in the registry, not estimates that serious events are impossible or that risk is absent.

The same summary lists other adverse events affecting 2 participants in the active group and 1 in the placebo group. Those other events are distinct from the serious adverse-event category in the summary. The primary endpoint is specifically treatment-related adverse events; the record does not provide enough event-level detail to establish that the other-event counts and the primary endpoint have identical definitions or classification rules.

The list of leading serious-event terms is empty. The record does not provide descriptions of the non-serious events, their severity, onset, duration, or adjudication. With the small number of participants recorded, zero serious events should be read as an observation in this study, not as a precise estimate of serious-event risk. These figures describe the registry record and do not support a broader safety conclusion.

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

The result establishes what the registry reports for the primary outcome: 2 participants in the active group and 1 in the placebo group had treatment-related adverse events recorded over 28 days. The adverse-event summary also records no serious adverse events and no deaths in either group. These observations provide a limited description of events in the enrolled study population.

The result does not establish that Nu-3 gel caused or prevented an event. A randomized design can support comparisons when the methods and analysis are reported and the data provide adequate information, but randomization alone does not turn a small set of counts into a precise estimate. The registry has no posted inferential comparison for this binary outcome, so it does not quantify the uncertainty around a treatment effect.

The result also does not show whether the 5% and 10% concentrations differ. The active group combines the doses for the posted primary outcome, and dose-specific counts are not reported. Nor does this endpoint measure ulcer healing, infection outcomes, or another efficacy outcome. The study's stated focus is safety and tolerability.

The study status is terminated, but the reason is not reported in the registry record. Without that information, the status should not be interpreted as evidence for or against the treatment. Likewise, the absence of posted analysis details does not prove that no analysis was conducted; it means that no such analysis is available in this registry record.

Overall, the counts are descriptive and limited to the participants and timeframe recorded. They do not justify medical advice, a treatment decision, or a conclusion about effectiveness. A more informative assessment would require adequately reported methods, event details, and comparative uncertainty, none of which can be inferred from these counts alone.

14. Why This Trial Matters Statistically

Early clinical studies often prioritize safety and tolerability while gathering initial information about an intervention. This study's primary outcome reflects that purpose: it counts participants with treatment-related adverse events after topical Nu-3 gel use on chronic diabetic foot ulcers. Such an outcome is relevant to understanding what events were recorded during the stated treatment period, even when the study cannot provide a precise comparative estimate.

The record also illustrates why study design labels must be read alongside the available outcome data. Randomization and masking can support fair comparisons in principle, but their value depends on implementation, sample size, outcome measurement, and transparent analysis. The registry identifies a randomized study and reports masking metadata, yet does not provide enough detail to evaluate allocation procedures, masked roles, or the statistical analysis.

The arm-level result combines both active concentrations, so the listed counts do not answer whether the outcome varied by dose. The terminated status and absence of a posted inferential comparison further limit what can be learned. These are not grounds to dismiss the observations; they clarify that the observations are preliminary descriptive data rather than a conclusive comparison.

For biostatisticians and clinical researchers, this record underscores the importance of reporting participant flow, outcome definitions, analysis populations, event details, missing-data handling, and uncertainty estimates. Those elements let readers distinguish an observed count from a reliable estimate of a treatment effect. In their absence, careful interpretation means staying close to the registry entries and recognizing the boundaries of the evidence.

15. 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 main limitation is the very small enrollment recorded in the registry: 3 participants, with 2 listed in the active group and 1 in the placebo group. Each participant therefore has a strong influence on the descriptive group counts, and the record does not provide a usable inferential comparison for the binary outcome. There is no reported confidence interval or p-value to describe comparative uncertainty.

The active group includes 5% and 10% gel, but the posted primary outcome is not separated by dose. The record does not report how participants were allocated across those concentrations, how dose escalation proceeded, or what criteria governed escalation. A dose-specific safety pattern cannot be assessed from the arm-level counts.

The study is marked terminated, but the reason for termination is not reported in the registry record. Participant flow, withdrawals, missing outcomes, baseline characteristics, and analysis populations are also not reported. The absence of these details makes it difficult to assess representativeness, completeness of outcome ascertainment, or the influence of exclusions.

The record provides limited event detail. It does not describe the non-serious events, their severity or timing, or the criteria used to determine treatment relatedness. It also does not explain the difference between quadruple masking in the metadata and double-blinding in the title. The statistical analysis plan, sample-size justification, and multiplicity procedures are not reported. Together, these limitations mean the results support only a narrow descriptive reading of the recorded counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Nu-3 Topical Gel for Treatment of Diabetic Foot Ulcer — NCT05276401.
• Registry record last updated 2024-01-30; status last verified 2023-12.
• Results first posted 2024-01-30.
• 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.

19. Record Summary

NCT05276401 is a terminated phase 2a randomized, placebo-controlled study of topical bisphosphocin Nu-3 gel for clinically noninfected chronic diabetic foot ulcers. The registry describes active 5% and 10% gel and placebo gel, applied twice daily for 28 days. Enrollment is listed as 3, with 2 participants in the active group and 1 in the placebo group. The recorded start date is 2022-03-11, and primary completion is 2022-05-18.

The primary outcome counts participants with treatment-related adverse events over 28 days, assessed using CTCAE v4.0. The posted counts are 2 for active and 1 for placebo. The adverse-event summary lists no serious adverse events and no deaths in either group, while other adverse events affected 2 active-group participants and 1 placebo-group participant. No two-arm inferential comparison is posted. The reason for termination and further analysis details are not reported in the registry record.