Dose-Finding Study of Intranasal Insulin in Healthy Participants Insulin in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose-Finding Study of Intranasal Insulin in Healthy Participants Insulin in Healthy Participants (NCT05062785), a na phase 1 study. The primary outcome is Severe Hypoglycemia.

2. Clinical Question

This framing matters because the study is a dose-finding investigation, not a trial designed to estimate a treatment effect against a randomized control. Its primary outcome concerns a safety threshold rather than a measure of clinical benefit. The registry lists change in blood glucose at selected visits and dose levels as secondary outcomes, but the numerical results for those outcomes are not reported in the registry record.

3. Trial Design

The registry identifies NCT05062785 as a Phase 1, open-label dose-finding study of intranasal insulin in healthy participants. It reports a sequential model and no masking. The study is marked completed. Its enrollment is listed as 24; that figure is the registry enrollment entry and should not be treated as the count of exposures at each dose.

The study summary says participants would receive intranasal regular insulin as drops in the nostrils. The arm description says 11 possible doses would be tested, ranging from 0 to 1000 U. The posted adverse-event results list dose levels of 100 Units, 200 Units, 400 Units, 500 Units, 600 Units, 800 Units, 900 Units, and 1000 Units. These entries are dose-level safety summaries, not randomized treatment arms assigned for a balanced comparison.

The primary endpoint timeframe was within 4 hours of dosing during each of 5 visits. The study also lists secondary blood-glucose-change outcomes at selected dose and visit combinations: Study Visit 1 at 100 Units, 200 Units, and 400 Units; Study Visit 2 at 400 Units and 600 Units; Study Visit 3 at 600 Units and 800 Units; and Study Visit 4 at 800 Units. The registry lists 31 outcome measures overall.

Study start is recorded as 2021-10-04, and primary completion as 2022-04-25. The registry does not report a detailed dose-escalation rule, the order in which participants received doses, or the number of participants exposed at each visit. Allocation is listed as NA, so the registry record does not support treating the dose groups as randomized or as a conventional control comparison.

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: The dosing schedule for each cohort was based on the occurrence of SAEs in the previous cohort. If no SAE occurred in any of the cohort's participants, then the dose escalation schedule for the next cohort was weighted towards higher doses and excluded a lower dose. One participant in Cohort 2 did not attend the final visit after Cohort 3 had already begun, so Cohort 3's dosing was not adjusted. Only Cohort 4 adaptively shifted to higher doses.

Study Visit 1

Washout 1 (Up to 10 days)

Reasons for not completing this period:

Study Visit 2

Washout 2 (Up to 10 days)

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 Severe Hypoglycemia, measured over Within 4 hours of dosing during each of 5 visits.

The primary endpoint is the count of participants who experienced severe hypoglycemia within 4 hours after dosing during each of 5 visits. The registry defines the event as blood glucose below 45 mg/dL and identifies it as a dose-limiting toxicity. In a dose-finding study, an event designated as dose limiting can inform safety assessment as doses are considered; the registry does not report a specific rule for using events to select or stop doses.

The endpoint is binary at the participant level: a participant either meets the stated severe-hypoglycemia definition during the specified observation window or does not. Reporting a count is useful for making the observed event burden visible, particularly when an event is considered important for tolerability. It does not, by itself, describe the full glucose response or establish how likely the event would be in a different population or setting.

The registry record reports the endpoint definition and timeframe, but does not provide a separate primary-outcome analysis with an estimate of uncertainty. The dose-level serious adverse-event entries show no serious events reported in the listed groups. Those entries should not automatically be substituted for the primary endpoint result: serious adverse events and the specifically defined severe-hypoglycemia endpoint are distinct reporting concepts. The numerical results for the secondary blood-glucose-change outcomes are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as sequential and open label. In general, a sequential dose-finding design evaluates doses in an ordered process, with later study decisions potentially informed by earlier observations. The registry record does not report the actual escalation algorithm, its decision thresholds, or whether any formal stopping rule was used. Those details should not be inferred from the design label alone. Open-label means masking is listed as none; the record does not describe any procedure intended to conceal dose or treatment identity.

What does a participant count represent?

The primary endpoint is a count of participants meeting a binary event definition. For each participant and relevant observation window, severe hypoglycemia is defined by blood glucose below 45 mg/dL. Counts are straightforward to interpret as observed events, but a count alone does not convey precision. A proportion would also require a clearly defined denominator, and a statistical comparison would require a suitable design and analysis method. The registry does not provide a separate endpoint analysis or confidence interval.

There is an important distinction between participant counts and repeated exposure records. The endpoint timeframe includes each of 5 visits, while adverse-event results are presented by dose. If a participant could contribute observations at more than one visit or dose, those observations may be correlated rather than independent. The registry does not report how repeat observations were represented in the dose-level denominators or analyses. Without that information, adding dose entries or treating each entry as an independent participant count would be unjustified.

How should zero-event entries be read?

A zero count means no event was recorded in the corresponding reported group. It does not establish that the underlying event risk is zero. In general, uncertainty around an event rate depends on the amount of information and the way observations were collected. A confidence interval expresses a range of values compatible with the data under a statistical method and its assumptions; it is not a guarantee that the true value lies within that range. No confidence intervals for the posted safety counts are reported in the registry record.

When events are rare or absent, estimates can be imprecise and standard methods that rely on large-sample approximations may perform poorly. The record does not identify a method for estimating event probabilities, handling zero cells, or accounting for repeated visits. It would therefore be inappropriate to attach a model-based risk estimate to these counts without additional data and a justified analysis plan.

Why is a randomized comparison not available?

Allocation is listed as NA, and the study is not masked. The record explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. In general, random allocation can help balance measured and unmeasured factors between treatment groups. Without it, observed differences between dose entries may reflect differences in who was exposed, when exposure occurred, or other features of the sequential process. The record does not report enough detail to distinguish these possibilities.

Even a numerical difference between two listed dose groups would not by itself estimate a causal dose effect. The groups have different at-risk counts, and the registry does not describe the allocation or escalation process. No adjusted analysis is reported. The record lists 0 analyses, so there is no reported inferential model or test to evaluate alongside the descriptive counts.

What do planning assumptions mean?

General sample-size calculations ask how much information a future study might need to detect a specified effect under stated assumptions. The registry’s sample-size assumptions describe an 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 effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed or sized according to those assumptions. No numerical planning results are reported in the registry record.

These assumptions also do not resolve whether a two-arm randomized comparison is appropriate for a sequential dose-finding study. The registry does not report the trial’s own sample-size justification or statistical plan. It does not report interim analyses, dose-selection criteria, multiplicity procedures, or a model for repeated glucose measurements. Their absence from the record means those methods cannot be evaluated from the posted information.

For the secondary blood-glucose-change outcomes, repeated measurement and multiple dose-visit combinations could raise questions about within-participant correlation and multiplicity. In general, repeated observations from the same participant are not necessarily statistically independent, and testing many outcomes can increase the chance of chance-positive findings if no adjustment or prespecified hierarchy is used. The registry lists these outcomes but does not report their numerical results or an analysis method. No conclusion about the handling of correlation or multiplicity is warranted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 31 outcome measures, including the primary severe-hypoglycemia endpoint and secondary blood-glucose-change outcomes at selected visits and doses. It reports 0 analyses. The record does not describe a prespecified hierarchy of outcomes, a multiplicity adjustment, or a strategy for interpreting results across the listed measures. In general, examining many outcomes can make isolated findings harder to interpret unless the analysis plan specifies how the family of tests will be handled. No such plan is reported in the registry record.

The registry describes the primary endpoint timeframe as within 4 hours of dosing during each of 5 visits, but does not explain how observations across visits were combined or how repeated observations from the same participant were handled. It also does not report an analysis population, participant flow by dose, or a missing-data method. Whether all enrolled participants contributed to each outcome, and how missing glucose measurements or incomplete visits were treated, is not reported in the registry record.

The dose-level safety entries include different at-risk counts. The record does not state whether those counts refer to unique participants, dosing occasions, or another unit, nor does it explain how repeat exposure was handled. Without these details, denominators should not be pooled and dose-level event counts should remain descriptive. A statistical plan, interim analysis procedures, and rules for selecting a maximum tolerated dose are not reported in the registry record.

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.

Most frequent non-serious adverse event terms

The registry reports serious adverse events and other adverse events separately. For serious adverse events, the listed affected count is 0 at every reported dose level: 100 Units, 200 Units, 400 Units, 500 Units, 600 Units, 800 Units, 900 Units, and 1000 Units. The deaths count is also 0 in each listed group. These are registry-reported counts, not proof that the underlying risks are absent.

For other adverse events, 2 affected are reported at 600 Units, while 0 are reported at each of the other listed dose levels. The registry does not identify the terms for those events in the posted serious-event term list, which is empty. The entries therefore do not support identifying what the 2 other events were or whether they were related to insulin.

The at-risk counts vary by dose: 4 at 100 Units, 14 at 200 Units, 24 at 400 Units, 1 at 500 Units, 23 at 600 Units, 22 at 800 Units, 5 at 900 Units, and 22 at 1000 Units. The record does not clarify the denominator unit or how participants could contribute across doses. These figures should not be added or read as independent randomized groups. Severe hypoglycemia is separately defined as the primary endpoint; serious-adverse-event counts should not be taken as a substitute for its complete analysis.

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

The registry record describes a completed Phase 1, open-label, sequential study of intranasal regular insulin in healthy participants. It identifies severe hypoglycemia, defined as blood glucose below 45 mg/dL within 4 hours of dosing during each of 5 visits, as the primary endpoint and a dose-limiting toxicity. Its posted safety entries report no serious adverse events or deaths in the listed dose groups and report 2 other adverse events at 600 Units.

Those observations describe the entries in the registry; they do not establish that severe hypoglycemia or other safety events cannot occur. The record does not provide a separate primary-endpoint analysis, uncertainty estimates, or numerical results for the listed blood-glucose-change outcomes. It also does not report a statistical analysis of a dose-response relationship. The available information therefore does not quantify the precision of a risk estimate or show how the outcomes varied over time and dose.

The study is not a randomized comparison. Dose groups should not be interpreted as equivalent treatment arms, and differences in their reported counts cannot be assigned to dose alone. The record does not give enough information about dose allocation, repeated exposures, or denominator definitions to support a causal comparison. The enrollment entry of 24 does not mean each listed dose group contains the same number of participants, and dose-level counts should not be combined.

The record states that the study aimed to assess safety and tolerability and determine the maximum tolerated dose, but it does not report the decision rule or a maximum tolerated dose conclusion. It also does not report efficacy outcomes that would establish clinical benefit. The results should consequently be read as descriptive safety information from a specific healthy-participant dose-finding study, rather than as proof of safety in other populations or evidence of treatment benefit.

13. Why This Trial Matters Statistically

This study raises statistical questions that commonly arise in early dose-finding research. The goal described in the registry is to assess safety and tolerability across possible doses, with severe hypoglycemia designated as a dose-limiting toxicity. That focus differs from a conventional randomized efficacy comparison: the key issue is how safety observations inform dose assessment, not whether an intervention outperforms a control group.

The sequential model makes the relationship between design and analysis especially important. In general, decisions about subsequent doses may depend on earlier observations, so the order of exposure and decision rules can affect how results should be interpreted. The registry does not report those rules. Without them, readers cannot reconstruct the dose-finding procedure or assess how a maximum tolerated dose would have been selected.

Repeated visits and dose-specific entries also highlight the need to define the unit of analysis. A participant count, an exposure count, and a visit-level observation are not interchangeable. The record describes a primary endpoint measured within a specified post-dose window during repeated visits, but does not explain how the dose-level denominators relate to participants or repeat exposures. This limits how counts can be compared and prevents a reliable reconstruction of precision.

Finally, zero reported serious events are descriptive evidence, not a guarantee of no risk. Small or unevenly represented dose groups can leave uncertainty, and the registry does not provide confidence intervals or inferential analyses. The study is statistically informative as a case in why early dose-finding results require careful attention to outcome definitions, denominator structure, and reporting of design rules. The record’s limitations constrain the conclusions that can be drawn from its counts.

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 registry record gives a concise design description but not the protocol-level detail needed to reproduce the dose-finding process. It does not report how doses were assigned, the sequence of exposure, escalation or stopping criteria, or the rule used to determine a maximum tolerated dose. Although it identifies a sequential design and 11 possible doses ranging from 0 to 1000 U, the posted adverse-event entries cover selected dose levels and do not explain how those entries map to the full possible-dose range.

The at-risk counts differ across listed doses, and the record does not explain whether they count unique participants, treatment exposures, or another analysis unit. It does not report participant flow by visit and dose, how participants could contribute to more than one dose, or how repeated observations were handled. This prevents a clear assessment of denominators and precludes pooling counts or treating the dose groups as independent.

The primary endpoint is defined, but a separate primary-outcome result and uncertainty estimate are not reported. The registry also does not report numerical results for the secondary blood-glucose-change outcomes, missing-data handling, analysis populations, or methods for repeated measurements. With 31 outcome measures listed and 0 analyses reported, the record does not show how multiplicity was addressed or how results across outcomes were interpreted.

Finally, the study is open label and not randomized, and the registry warns that the arms are not a like-for-like control comparison. The available counts therefore do not support causal comparisons across doses. The sample-size assumptions describe planning illustrations, not the study’s documented design justification; the registry record does not report its own statistical plan or sample-size rationale.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dose-Finding Study of Intranasal Insulin in Healthy Participants Insulin in Healthy Participants — NCT05062785.
• Registry record last updated 2026-03-27; status last verified 2025-09.
• Results first posted 2026-03-27.
• 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

NCT05062785 is a completed Phase 1, open-label, sequential dose-finding study of intranasal regular insulin in healthy participants. The registry lists enrollment as 24, study start as 2021-10-04, and primary completion as 2022-04-25. The intervention is described as intranasal insulin administered as drops in the nostrils, with 11 possible doses ranging from 0 to 1000 U.

The primary endpoint is the count of participants experiencing severe hypoglycemia, defined as blood glucose below 45 mg/dL within 4 hours of dosing during each of 5 visits. It is identified as a dose-limiting toxicity. The posted dose-level safety entries report 0 serious adverse events and 0 deaths at each listed dose, with 2 other adverse events reported at 600 Units. The record lists 31 outcome measures and 0 analyses.

The registry does not report a randomized comparator, a detailed dose-escalation or maximum-tolerated-dose rule, a separate primary-endpoint analysis, confidence intervals, or numerical secondary glucose-change results. The dose-level entries are descriptive and do not establish causal differences between doses.