Transdermal Insulin Response In Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transdermal Insulin Response In Healthy Volunteers (NCT04857320), a na early/phase 1 study. The primary outcome is Postprandial Serum Glucose in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin Averaged Per Subject.

2. Clinical Question

This is a pharmacodynamic question: it concerns a measured glucose response following exposure to insulin, rather than a comparison of clinical outcomes between treatment groups. The primary outcome is described as an average postprandial serum glucose measure, expressed in mg/dL, averaged per subject. The timeframe refers to pre-dose baseline and a mean of readings over 3.5 hours after dosing.

The record does not report the numerical glucose results, the size or direction of any baseline change, or an uncertainty interval. It therefore does not establish from the available record how large or consistent any response was. The dose descriptions identify what was planned for application to the skin, but do not by themselves show the amount of insulin absorbed or the glucose response associated with any dose.

3. Trial Design

The registry identifies NCT04857320 as a completed study sponsored by Transdermal Delivery Solutions Corp. The recorded start date is 2021-03-12, and the primary completion date is 2021-11-15. The registry phase is Early Phase 1. The official title, however, calls the study Phase II and describes it as physician-initiated, randomized, multiple-dose, single-period, and dose-ranging. That difference in phase labels is present in the record and is not resolved there.

The registered model is single group, allocation is listed as NA, and masking is listed as none. The record also flags that this is not a randomized comparison and that its arms are not a like-for-like control comparison. Although the official title uses the word randomized, the recorded design information does not identify a randomized allocation between treatment and control arms. The results should therefore not be read as a randomized treatment-versus-control estimate.

The main experimental description says each subject will receive doses applied to the skin of 0.075 IUs per kilogram of body weight, 0.1 IUs per kilogram of body weight, and 0.15 IUs per kilogram of body weight. The primary outcome description associates baseline with Day 1 and the three doses with Day 2, Day 3, and Day 4, respectively. This describes a sequence of measurements within the study, not a parallel-group comparison. Further details about dose order, washout, administration conditions, or sequence effects are not reported in the registry record.

The record states that 7 healthy individuals were recruited and entered, and that data from 2 subjects were not included because of non-compliance with the protocol. It does not identify which measurements were missing or describe how the exclusion was handled in the primary analysis.

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: 7 Volunteers were asked to undergo a physical exam including a complete metabolic panel via blood sample.

Overall Study

Analysis population for the primary outcome, as defined in the registry: We recruited and entered 7 healthy individuals into the study. We did not include data from 2 Subjects due to non-compliance with the protocol.

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 Postprandial Serum Glucose in mg/dL as a Response to Small Doses (0.075 to 0.15 IUs/Kg) Human Insulin Averaged Per Subject, measured over Pre-dose Baseline & a Mean of readings over 3.5 hours.

The primary endpoint is postprandial serum glucose in mg/dL in response to small doses of human insulin, averaged per subject. The record describes glucose measurement by continuous glucose monitor and a comparison of pre-dose baseline with a mean of readings over 3.5 hours after each dose. It associates baseline with Day 1, followed by Dose 1 on Day 2, Dose 2 on Day 3, and Dose 3 on Day 4.

Glucose is a pharmacodynamic measure in this study because it captures a physiological response following insulin exposure. Repeated measurements over a post-dose period can describe the pattern of glucose readings more fully than a single reading. Averaging readings can provide a concise summary, but it can also conceal variation over time. The registry does not state how the time-series readings were processed, whether the primary analysis produced a separate summary for each dose, or how any readings outside the stated period were handled.

The endpoint lists a mean as its summary measure and full range as its dispersion measure. Those labels indicate the intended kinds of summaries, but the registry record does not report the actual mean, range, or a contrast with baseline. Without those values, the magnitude and precision of the endpoint cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean represent?

As a general statistical concept, a mean is a measure of the center of a set of observations. In this study, the endpoint description refers to an average of postprandial glucose readings and an average per subject. Averaging can make a series of readings easier to summarize, but it discards detail about the timing and shape of the readings. Two participants could have similar averages even if their readings changed in different ways over the measurement period. The registry record does not describe the exact algorithm used to derive each subject's average.

The endpoint also names full range as its dispersion summary. In general, a range describes the span from the lowest to highest value in the observations being summarized. It is sensitive to extreme readings and does not describe how observations are distributed between the endpoints. No numerical range is reported in the registry record, so the amount of observed variability cannot be assessed.

What would a baseline comparison mean?

In general, a within-person baseline comparison uses each participant's pre-dose measurement as a reference for later measurements. This can account for some stable differences between people, since the comparison is made within the same individual. It does not, by itself, control for changes over time, measurement conditions, or other factors that differ between baseline and follow-up. A separate control group can help address some of those questions, but no like-for-like control comparison is described in this record.

The outcome description connects Day 1 baseline with measurements following doses on Day 2, Day 3, and Day 4. Because measurements are described across successive days in the same study, analyses may need to consider the relationship among observations from the same person. In general, repeated observations from one participant are not independent in the same way as observations from different participants. The registry does not report the statistical method used to account for this dependence, or whether the endpoint was analyzed separately for each dose or combined across doses.

Why do uncertainty intervals matter?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical procedure. It helps readers distinguish an estimate's central value from the range of values reasonably compatible with the data and method. A narrow interval indicates greater precision than a wide interval, though neither alone determines whether a result is important. The registry record does not report confidence intervals for the primary outcome, so precision cannot be evaluated from the posted results.

A p-value, when reported, is a measure calculated under a statistical model and a null hypothesis. It does not give the probability that the null hypothesis is true, and it does not measure the magnitude or clinical importance of an effect. No primary-outcome p-value or hypothesis test is reported in the registry record. It is therefore not appropriate to infer statistical significance or lack of significance.

What do the planning assumptions indicate?

The registry's sample-size assumptions describe a planning illustration based on the 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. These assumptions are not a description of the registered single-group design: the trial record lists allocation as NA and identifies no like-for-like control comparison. Such calculations are planning illustrations, not observed power and not evidence that the study had a particular probability of detecting a response. Their outputs do not establish what the trial observed.

In general, a normal approximation uses a mathematical distribution to estimate uncertainty or required sample size. Its suitability depends on the data and analysis conditions. Equal allocation between two arms is an assumption for a hypothetical two-arm calculation, not a feature that can be inferred for this single-group study. The registry record does not report a sample-size justification for the trial itself, the calculation method used in its design, or any protocol-based target for detecting a glucose response.

Why can multiple outcomes or analyses complicate interpretation?

When investigators examine several outcomes, doses, time points, or statistical contrasts, the chance of finding an apparently notable result by chance can increase if no approach to multiplicity is specified. General approaches include defining a primary contrast in advance or adjusting inference across a defined family of tests. Which approach is suitable depends on the study question and analysis plan. The registry lists 3 outcome measures and 7 analyses, but it does not report how those analyses map to outcomes, doses, or time points, nor does it describe a multiplicity strategy. No adjustment or unadjusted interpretation should be assumed.

Overall, the statistical labels in the registry identify intended summaries and planning assumptions, but the absence of numerical endpoint results and an analysis description prevents an independent assessment of the glucose estimates, their uncertainty, or the handling of repeated measurements.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and 7 analyses. It does not report how the analyses correspond to specific outcomes, dose levels, measurement times, or contrasts. A prespecified hierarchy of outcomes, a family of hypotheses, and any multiplicity adjustment are not reported in the registry record. Without that information and the analysis results, readers cannot determine whether a reported finding would represent a primary planned test or one of several examined comparisons.

The primary outcome description states that data from 2 subjects were not included because of protocol non-compliance. The record does not describe which outcome observations were missing, the extent or timing of missingness, or whether the omitted data were absent for all doses or only some measurements. It also does not report imputation, sensitivity analyses, or another method for addressing missing outcome data. The reasons are described as non-compliance, but further details are not reported in the registry record.

The number of participants in the primary analysis is not reported in the registry record. The statement that 7 individuals entered the study and data from 2 were excluded does not establish which observations were included in each endpoint analysis, so an analyzed sample size should not be inferred. The safety section separately records 7 participants at risk; that safety denominator should not be assumed to be the denominator for the glucose outcome.

The record does not describe the analysis population definitions, such as whether an intention-to-treat or per-protocol approach was used. It also does not specify how protocol deviations, incomplete monitoring, or repeated measurements were handled. These omissions limit the ability to assess whether the analyses reflect all enrolled participants or a subset and how robust the endpoint summaries may be to missing data.

11. 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.

The registry records 0 serious adverse events among 7 participants at risk in the Main Experimental group. It also records 0 participants affected by other adverse events among 7 at risk, and 0 deaths. No top serious adverse-event terms are listed. These are the safety counts reported in the registry record.

A zero count means that no events of the specified type were recorded in the listed group for the registry entry. It does not demonstrate that the event risk is absent, and it does not provide a precise estimate of risk in a broader population. In general, safety estimates are less precise when based on few participants, especially for uncommon events. The registry does not provide confidence intervals or further event-level detail that would quantify uncertainty.

The safety denominator is reported as 7 at risk. It should not be substituted for the outcome-analysis denominator, which is not reported in the registry record. The record also does not provide additional details about the duration or completeness of safety surveillance, or clarify how events were collected and classified beyond the listed categories. These counts describe what was registered, rather than establishing that no unrecorded or unobserved events occurred.

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

The study record documents an investigation of transdermal human insulin in healthy volunteers, with a primary focus on postprandial serum glucose relative to baseline. It specifies three dose levels and a measurement period described as a mean of readings over 3.5 hours. These details show the intended pharmacodynamic question and the way the endpoint was framed.

The registry record does not report the numerical glucose results. It therefore does not show the magnitude, direction, variability, or precision of any post-dose change. No conclusion about whether glucose changed, or by how much, can be drawn from the design description alone. Missing results should not be interpreted as a zero effect or as evidence that no response occurred.

The single-group design and lack of a like-for-like control comparison also constrain interpretation. A baseline reference is useful for describing within-person measurements, but it does not provide the same comparison as a concurrent control group. The registered information cannot separate an apparent time-related change from other influences, and the dose schedule alone cannot establish a dose-response relationship.

The record states that 2 subjects' data were not included because of protocol non-compliance, but does not report the primary analysis population or details of missing measurements. This makes it difficult to assess how representative the endpoint summaries would be of those who entered the study. The safety counts report no recorded serious adverse events, other adverse events, or deaths in the listed group, but do not establish the absence of risk beyond the recorded observations.

In short, the registry information describes the study's question and selected design and safety details, but does not give the primary outcome estimates required to characterize the measured response. It supports neither a numerical estimate of effect nor a conclusion about how precisely such an estimate was made.

13. Why This Trial Matters Statistically

This study is statistically notable because its title and registry design information do not align neatly. The official title describes a randomized, multiple-dose, single-period study, while allocation is listed as NA, the model is single group, and the record explicitly notes that this is not a randomized comparison. That distinction matters: a within-person comparison to baseline answers a different question from a randomized comparison against a concurrent control group.

The record also illustrates why an endpoint definition is not the same as an endpoint result. It gives the glucose measure, unit, averaging description, baseline reference, post-dose timeframe, and schedule across Day 1 through Day 4. Yet the numerical results and statistical analysis are not reported in the registry record. Without them, readers cannot evaluate effect magnitude or precision, regardless of how clearly the measurement is described.

The handling of non-compliance is another important statistical issue. The record says that data from 2 subjects were not included, while it lists 7 participants at risk for safety outcomes. Clear reporting of analysis populations and missing observations is essential for understanding which data underpin an estimate and whether exclusions could affect it. Those details are not reported for the primary endpoint.

Finally, the planning assumptions describe equal allocation between two arms even though the registered model is single group. This is best understood as a hypothetical planning framework rather than a description of the study's actual comparison. Statistical interpretations depend on matching methods and assumptions to the design. The registry record supplies too little analysis detail to evaluate that match for the glucose outcome.

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 most direct limitation is that numerical primary-outcome results are not reported in the registry record. There are no glucose means, ranges, baseline contrasts, confidence intervals, or p-values to assess. Accordingly, the magnitude and precision of the measured response cannot be described.

The study is recorded as a single-group design with allocation listed as NA and no like-for-like control comparison. The official title's use of randomized does not resolve this issue, because the registered design details do not identify a randomized control group. Baseline comparisons can describe measurements over time but do not provide the same protection against time-related influences as a concurrent control comparison.

The primary outcome population is also unclear. The record says that 7 healthy individuals entered and that data from 2 were not included because of non-compliance, but it does not state the analysis denominator or explain which dose and time-point observations were available. Missing-data methods and sensitivity analyses are not reported.

The endpoint is described as an average over readings during 3.5 hours, but the monitoring-data processing method and the handling of incomplete or unusual readings are not reported in the registry record. Nor is it clear whether estimates were calculated separately for each dose or combined. The record lists 3 outcome measures and 7 analyses but does not map them or describe multiplicity handling.

Finally, the registry phase label is Early Phase 1 while the official title says Phase II, and the planning assumptions describe equal allocation between two arms despite the single-group model. These discrepancies and omissions limit interpretation of both the design and the analysis. The record does not report additional protocol details that would resolve them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Transdermal Insulin Response In Healthy Volunteers — NCT04857320.
• Registry record last updated 2023-10-23; status last verified 2023-10.
• Results first posted 2023-10-10.
• 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

NCT04857320 is recorded as a completed study sponsored by Transdermal Delivery Solutions Corp. It concerns transdermal human insulin in healthy volunteers, with a primary outcome of postprandial serum glucose measured by continuous glucose monitor and described relative to pre-dose baseline. The record gives three skin-applied dose levels and a post-dose measurement period of 3.5 hours.

The registered model is single group, allocation is NA, and masking is none. The record says 7 individuals entered and data from 2 were not included because of protocol non-compliance. It records 0 serious adverse events, 0 other adverse events, and 0 deaths among 7 participants at risk.

Numerical primary-outcome results, analysis-population details, missing-data methods, and the statistical analysis plan are not reported in the registry record. The registry phase label and the phase in the official title differ, and the title's reference to randomization is not supported by the recorded comparison design.