Comparison of Insulin Tregopil (IN-105) With Insulin Aspart in Type 2 Diabetes Mellitus Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Insulin Tregopil (IN-105) With Insulin Aspart in Type 2 Diabetes Mellitus Patients (NCT03430856), a randomized phase 2, phase 3 study. The primary outcome is Change From Baseline in HbA1c at 24 Weeks (Part 1).

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, open-label Phase II/III study sponsored by Biocon Limited. Its registered title describes a comparison of insulin tregopil (IN-105) with insulin aspart in patients with type 2 diabetes mellitus. The brief summary specifies that participants were on stable doses of metformin and insulin glargine. The registry lists an enrollment of 143.

The study was organized in Part I and Part II. The brief summary gives an approximate duration of 37 weeks for Part I and for Part II, respectively. The primary endpoint belongs to Part 1 and was change from baseline in HbA1c at 24 weeks. The record does not provide results for that endpoint, nor does it explain the aims or findings of Part II in the information.

The listed treatment groups were insulin tregopil at 45mg, insulin tregopil at 30mg, and insulin aspart. The tregopil descriptions state that each tablet had a strength of 15mg. Insulin aspart was described as a pre-filled pen at 100 U/L. These descriptions identify the registered treatment groups and formulations; additional dosing instructions are not reported in the registry record.

Randomization can help balance measured and unmeasured baseline characteristics across groups on average, although chance imbalances remain possible. Because masking was absent, participants and study personnel knew the assigned treatment. This can affect experiences and reporting, particularly for outcomes involving judgment or participant reporting. HbA1c is a laboratory measure, but the registry record does not describe laboratory procedures or safeguards against measurement bias. The primary analysis was defined for the Part 1 full analysis set, using an intention-to-treat principle and retaining participants according to randomized assignment.

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 trial included an 8-week run-in period and a 24-week treatment period. During the run-in period, the subjects received insulin glargine along with metformin. In total, 143 subjects entered the run-in period, of these 52 subjects were run-in failures. Hence, 91 subjects were randomly assigned to each treatment arm.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis of this efficacy endpoint was based on the full analysis set (FAS). FAS included all randomized subjects in Part 1. The statistical evaluation of the FAS was to follow the intention-to-treat (ITT) principle and subjects contributed to the evaluation 'as randomized'.

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: Safety Analysis Set included all randomized subjects.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in HbA1c at 24 Weeks (Part 1), measured over Week 0, Week 24.

The primary endpoint was change from baseline in HbA1c at 24 weeks in Part 1. HbA1c is the percentage of glycosylated hemoglobin, reflecting glucose exposure over time rather than a single momentary measurement. It is commonly used in diabetes research as an indicator of longer-term glycemic status. The endpoint therefore asks whether average HbA1c moved over the treatment period and how that change compared between randomized groups.

For a continuous endpoint, a group mean summarizes the average observed change, while the standard deviation describes the spread of individual changes around that average. These summaries answer different questions: the mean describes the typical direction and magnitude at group level, while the standard deviation describes participant-to-participant variability. A comparison of means can estimate the average difference between randomized treatments, but its precision depends on the amount of information and variability in the data.

The registry specifies HbA1c change at Week 24, with baseline at Week 0, and identifies the full analysis set as the analysis population. It does not report the group means, standard deviations, treatment contrast, confidence interval, or significance test for the primary endpoint. Consequently, the endpoint definition can be described, but the size and precision of the observed comparison cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

The primary endpoint is a continuous measure: each participant’s HbA1c can change by a range of amounts in either direction. A mean change averages those individual changes within a treatment group. It provides a group-level description, not a claim that every participant changed by that amount. Individual responses can vary, which is why the registry also identifies the standard deviation as the measure of dispersion.

General: the standard deviation describes how dispersed observations are around their mean. A relatively broad spread means individual changes vary considerably; a narrower spread means they are more clustered. The standard deviation is not the same as the standard error or a confidence interval. The registry record identifies mean and standard deviation as the summary approach, but does not report their primary endpoint values.

What is the randomized comparison?

The trial used randomized allocation and a parallel-group model. In a parallel design, participants are assigned to a treatment group and the groups are compared over the study period. Randomization is intended to make treatment groups comparable at baseline on average, reducing confounding in the treatment comparison. It does not guarantee that every baseline characteristic will be identical, particularly in a study of limited size.

The primary analysis description says the full analysis set included all randomized subjects in Part 1 and was to follow the intention-to-treat principle. Participants were to contribute according to their randomized assignment. General: this approach seeks to preserve the benefits of randomization and estimates the effect of assignment to a treatment strategy. The record does not report adherence or deviations from assigned treatment, so their impact cannot be assessed.

How should uncertainty be understood?

General: a confidence interval expresses statistical uncertainty around an estimated effect under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval; an interval spanning values that would imply different practical conclusions may leave the comparison uncertain. A p-value addresses compatibility of data with a specified null hypothesis under an analysis model; it does not measure the probability that the null hypothesis is true, nor does it quantify clinical importance.

The registry record does not report the primary treatment contrast, confidence interval, or p-value. The precision and statistical evidence for the primary comparison therefore cannot be described. The record also does not report the detailed statistical model, covariate adjustment, handling of baseline HbA1c, or assumptions used to estimate the primary treatment contrast.

Why can over-dispersion matter?

General: over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variation than is present, standard errors may be too small and uncertainty may appear overstated. This issue is most relevant to outcomes modeled as counts or proportions. The primary endpoint is continuous and is described using a mean and standard deviation; no over-dispersion assessment or model details are reported in the registry record. It would not be appropriate to infer that over-dispersion was present or that a particular adjustment was used.

What can the safety counts tell readers?

The record lists the number at risk and the number affected for serious and other adverse events in each treatment group. These are descriptive counts. General: a count alone does not establish whether a treatment caused an event, and a group comparison needs context about event definitions, follow-up, exposure, and uncertainty. The registry record does not give serious adverse event terms, and the listed other-event counts are not accompanied by event descriptions in the information reported. The counts can be stated, but they do not support a comprehensive comparative safety analysis.

What do planning calculations mean?

General: a sample-size calculation is a design aid that estimates the amount of information needed for a chosen effect, variability, significance level, and power target under specified assumptions. The registry description of the planning illustration says it is based on the observed effect rather than the trial’s own design, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. Such planning values are hypothetical illustrations, not observed power and not evidence that the trial was designed around those assumptions.

The numerical inputs and resulting planning estimates are not reported in the registry record information. The trial’s own sample-size justification, assumed effect, assumed variability, and statistical planning rationale are not reported in the registry record. They should not be inferred from any retrospective illustration.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including HbA1c measures, hypoglycemia events, weight, lipid profile, post-prandial glucose excursion, treatment-emergent adverse events, and anti-drug antibody levels. When a study examines several outcomes or repeated time points, the chance of at least one apparently positive result can increase if each is tested separately. General: multiplicity methods can control or otherwise address that issue, but the appropriate approach depends on the objectives and prespecified analysis plan.

The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or a prespecified testing strategy. It also does not provide enough information to determine which secondary comparisons were formally tested or how any such tests were interpreted. The primary endpoint is specified at Week 24 in Part 1, while the listed secondary outcomes include other timeframes and measures; details of their analysis are not reported in the registry record.

The record states that the primary efficacy endpoint was analyzed in the full analysis set, including all randomized subjects in Part 1, under an intention-to-treat principle. It does not report the number with observed Week 24 HbA1c measurements, reasons for missing measurements, imputation methods, sensitivity analyses, or handling of treatment discontinuation. General: missing data can weaken a randomized comparison when the chance of being observed is related to health status or treatment response. Different assumptions about missing outcomes can lead to different estimates, so transparent reporting of the approach and sensitivity analyses is useful.

Other analysis populations, such as a per-protocol set or safety set, are not described in the primary endpoint information. Their definitions and results are not reported in the registry record. Thus, the stated intention-to-treat approach is identifiable, but the robustness of the result to missing data, deviations, and alternative analysis populations cannot be assessed.

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 lists serious adverse events by treatment group, with both the number at risk and the number affected. For insulin tregopil (IN-105) at 45mg, 31 were at risk and 0 were affected. For insulin tregopil (IN-105) at 30mg, 30 were at risk and 0 were affected. For insulin aspart, 30 were at risk and 0 were affected. No deaths were reported in these groups.

The registry also reports other adverse events: 5 affected participants in the 45mg tregopil group, 5 in the 30mg tregopil group, and 4 in the insulin aspart group. These counts are descriptive, and the record does not list the event terms in the information. They should not be read as evidence about causation or as a complete account of treatment harms.

General: zero recorded serious events does not establish that serious harm is impossible. Safety interpretation depends on the duration and completeness of follow-up, the event definitions, exposure, and the ability to detect uncommon events. The registry record does not provide serious event terms, detailed follow-up by group, or a statistical comparison of safety outcomes. The figures therefore describe recorded counts, not definitive comparative safety conclusions.

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

The registry record establishes that a randomized, open-label Phase II/III study compared insulin tregopil with insulin aspart in patients with type 2 diabetes mellitus on stable metformin and insulin glargine. It identifies change from baseline in HbA1c at 24 weeks in Part 1 as the primary endpoint and specifies the full analysis set and intention-to-treat principle for that efficacy analysis.

What the record does not establish is the numerical result of the primary comparison. Group means, standard deviations, an estimated difference, a confidence interval, and a p-value are not reported in the registry record. No conclusion about the direction, size, precision, or statistical evidence of a treatment difference can therefore be drawn from the primary endpoint information. Missing results should not be interpreted as showing either benefit, no effect, or equivalence.

The design features help frame, but do not replace, the results. Random allocation supports a comparison based on assigned treatment, while the open-label design leaves potential for awareness of treatment assignment to influence care or reporting. The primary outcome is a laboratory measure, but details of measurement and masking of laboratory assessment are not reported. The registry also does not report how missing outcome data were handled, which limits assessment of the stated analysis approach.

The safety figures show no serious adverse events recorded in the listed groups and some other adverse events. Those counts alone do not identify event types, establish treatment causality, or show how rates compare over equivalent exposure. They should be interpreted as a limited descriptive account rather than a complete safety assessment.

In short, the record allows readers to understand the question asked and some features of how it was to be answered. It does not report the primary efficacy estimates needed to answer the comparative question, nor enough safety detail for a broad evaluation of harms.

13. Why This Trial Matters Statistically

This trial is statistically notable because it places an oral insulin candidate, insulin tregopil, in a randomized comparison with insulin aspart while participants were receiving metformin and insulin glargine. The design makes the treatment contrast central: outcomes should be interpreted as a comparison between randomized groups, not as isolated changes within one group.

Its primary endpoint is a continuous measure, change in HbA1c from baseline to 24 weeks. Continuous outcomes can retain information about the range of participant responses, and mean change provides an interpretable group summary. But the mean alone would not show individual variability or uncertainty. Standard deviations, a between-group estimate, and its confidence interval are needed to judge how precisely the comparison was estimated. Those primary numerical results are not reported in the registry record.

The stated full analysis set and intention-to-treat approach are also important. An analysis that retains participants according to random assignment is designed to preserve the logic of randomization. Yet that principle does not resolve missing measurements or treatment deviations on its own; the record does not report how those issues were handled.

Finally, open-label allocation and the broad range of listed secondary outcomes matter for interpretation. Awareness of assigned treatment can affect some aspects of care and reporting, while multiple outcomes raise questions about how results were prioritized and interpreted. The registry record does not report a multiplicity strategy. These are reasons to examine the analysis details and numerical results carefully, rather than reasons to assume that bias or a false-positive finding occurred.

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 main limitation of the registry information is that it identifies the primary endpoint but does not report its numerical results. Without group estimates, a treatment contrast, or measures of uncertainty, the primary efficacy comparison cannot be independently interpreted. The record also does not give the result’s p-value or explain the statistical model used for the comparison.

The study was open label. Knowledge of treatment assignment can influence participant behavior, additional care, or reporting, although the primary endpoint is a laboratory measure. The record does not describe whether laboratory assessors were masked or provide details of laboratory quality control. The possibility of bias should therefore be recognized, but its presence or size cannot be determined from the record.

Information on missing primary endpoint data is not reported in the registry record. The number with observed measurements at Week 24, reasons for missing data, imputation approach, and sensitivity analyses are not described. The record states that the full analysis set included all randomized Part 1 subjects and followed an intention-to-treat principle, but the practical handling of incomplete observations remains unclear.

The registry lists several secondary outcomes, but does not report a multiplicity strategy or explain how those outcomes were prioritized. The detailed design and results for Part II are also not reported in the information. For safety, serious adverse event counts are available, but event terms and detailed descriptions of other adverse events are not reported. These limitations restrict assessment of efficacy, robustness, and comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparison of Insulin Tregopil (IN-105) With Insulin Aspart in Type 2 Diabetes Mellitus Patients — NCT03430856.
• Registry record last updated 2020-05-15; status last verified 2020-05.
• Results first posted 2020-05-15.
• 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

NCT03430856 is a completed, randomized, parallel-group, open-label Phase II/III study sponsored by Biocon Limited. It compared insulin tregopil (IN-105) with insulin aspart in patients with type 2 diabetes mellitus on stable doses of metformin and insulin glargine. The registry lists an enrollment of 143 and describes a study conducted in Part I and Part II.

The primary endpoint was change from baseline in HbA1c at 24 weeks in Part 1. The efficacy analysis was defined for the full analysis set of randomized Part 1 subjects and was to follow the intention-to-treat principle. Numerical primary endpoint results are not reported in the registry record, so the comparative effect and its precision cannot be assessed.

The listed groups were insulin tregopil at 45mg, insulin tregopil at 30mg, and insulin aspart. No serious adverse events or deaths were recorded in the listed groups; other adverse events were recorded, but detailed event terms are not reported in the information. Missing-data methods, detailed statistical modeling, and multiplicity procedures are not reported in the registry record.