Study to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity Between NKF-INS Glargine (G), United States (US)-Lantus®, and European Union (EU)-Lantus®: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity Between NKF-INS Glargine (G), United States (US)-Lantus®, and European Union (EU)-Lantus® (NCT06627478), a randomized phase 1 study. The primary outcome is Area Under the M1 Concentration-Time Curve From 0 to 12 Hours (AUC0-12h of M1).

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, double-blind, three-period, three-treatment, six-sequence crossover study. The trial enrolled 114 healthy participants and is recorded as completed. The registry dates are 2024-10-29 for study start and 2025-07-03 for primary completion. These dates describe the study record; they do not provide details about when individual participants received treatment or when analyses were performed.

Each treatment was a single subcutaneous dose: NKF-INS Glargine (G), US-Lantus®, or EU-Lantus®. In a crossover design, participants receive more than one treatment across separate periods, with treatment order arranged through sequences. This approach can allow within-participant comparisons, which may reduce the influence of stable differences between participants. That is a general feature of crossover designs, not a reported estimate of how much precision this particular design gained.

The registry identifies six sequences but does not report the sequence assignments, the number allocated to each sequence, or the randomization procedure. The length of each period, any washout interval, and the rationale for those design choices are not reported in the registry record. The registry also does not identify which people were masked or describe how masking was maintained. Double-blind is the recorded masking designation, but more specific operational details are unavailable.

The primary outcome was M1 AUC from 0 to 12 hours post-dose. The primary-outcome arm summaries each list 111 participants. This is distinct from the enrollment count and should not be read as a description of how many participants completed every period or entered every analysis; those analysis-population details are not reported in the registry record. The listed safety risk groups are 113 for US-Lantus®, 114 for NKF-INS Glargine (G), and 111 for EU-Lantus®.

The trial lists 24 outcome measures, including 23 posted secondary outcomes, and 62 analyses. Secondary outcomes include M1 maximum concentration, M1 AUC over several intervals, M1 time to maximum concentration, M1 AUC extrapolated to infinity, and insulin glargine concentration measures. The record does not explain how those outcomes or analyses were grouped into statistical families.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the M1 Concentration-Time Curve From 0 to 12 Hours (AUC0-12h of M1), measured over 0 to 12 hours post-dose.

The primary endpoint was the area under the concentration-time curve for M1 from 0 to 12 hours after dosing, recorded as AUC0-12h of M1. M1 is identified in the registry description as metabolite 21A-Gly-human insulin. The endpoint is expressed in hours*ng/mL, and the registered timeframe is 0 to 12 hours post-dose.

General statistical context: an area under a concentration-time curve combines concentration measurements across a specified time interval. It is used in pharmacokinetic studies to characterize overall exposure during that interval, rather than describing concentration at one moment. AUC0-12h therefore summarizes M1 exposure over the stated post-dose period. It does not, by itself, describe every feature of the concentration profile; the registry also lists measures such as maximum concentration and time to maximum concentration as secondary outcomes.

The primary arm summaries use geometric means and geometric coefficients of variation. A geometric mean is a way of summarizing positive measurements when variation is more naturally described on a multiplicative scale. The geometric coefficient of variation describes relative dispersion on that scale. These are summary measures, not individual participant values, and the reported arm summaries do not show the distribution of observations or the course of each participant’s measurements.

The endpoint was selected to compare M1 pharmacokinetics across the three treatments. The registry states that the comparison was intended to demonstrate pharmacokinetic similarity. It does not report the equivalence margins, the prespecified decision criteria, or the detailed analytical model used for the primary endpoint. Those omissions matter when interpreting whether an estimated ratio and its confidence interval satisfy the trial’s formal definition of similarity.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: pharmacokinetic comparisons often use ratios when the outcome is positive and treatment differences are naturally interpreted proportionally. A geometric mean ratio compares typical values on a multiplicative scale. A ratio near its no-difference reference indicates that the estimated geometric means are close on that scale. The confidence interval then communicates uncertainty in the ratio, rather than uncertainty in an arithmetic difference.

What does a geometric mean summarize?

A geometric mean is formed on a logarithmic scale and then expressed back on the original scale. This can be useful for measurements such as concentration or exposure, where values are positive and variability may be better represented by proportional changes than by fixed additive changes. The registry reports geometric mean values for AUC0-12h of M1 and geometric coefficients of variation. The posted means are 7.97 for US-Lantus®, 7.781 for NKF-INS Glargine (G), and 7.564 for EU-Lantus®. The corresponding geometric coefficients of variation are 32.48, 33.43, and 33.49.

The coefficient of variation is a relative measure of spread, rather than an expression of spread in the endpoint’s original units. A geometric coefficient of variation is tied to the log-scale description of variation. It should not be read as the range of participant values, nor does it identify how many participants had values above or below a particular point. Individual-level distributions are not reported in the registry record.

Why use a ratio and a confidence interval?

The posted analyses compare geometric means through ratios. For NKF-INS Glargine (G) and EU-Lantus®, the reported ratio is 102.914 and its 90% confidence interval is 96.886 to 109.318. For US-Lantus® and NKF-INS Glargine (G), the reported ratio is 97.723 and its 90% confidence interval is 93.153 to 102.518. A confidence interval helps show the precision of each comparison: it gives a range of estimates compatible with the observed data under the statistical model and its assumptions.

Equivalence testing asks whether the plausible treatment difference is contained within bounds defined in advance. Those bounds are essential: an estimate close to the no-difference reference does not by itself establish equivalence. The registry labels these as equivalence analyses, but equivalence margins and the rule for evaluating the intervals are not reported in the registry record. It is therefore possible to describe the ratios and intervals, but not to verify the trial’s formal equivalence criterion from the record alone.

How does crossover allocation affect the comparison?

General statistical context: in a crossover design, participants receive multiple treatments in different periods. Because each participant can contribute observations under more than one treatment, analyses may compare treatments while accounting for the participant’s own baseline level. This can be an efficient design when outcomes are stable enough across periods and treatment effects do not carry over in a way that distorts later measurements. The registry describes a randomized, double-blind, three-period, three-treatment, six-sequence crossover, but the analytical model and its treatment of participant, period, and sequence effects are not reported in the registry record.

Carryover and period effects are possible considerations in crossover studies. A carryover effect occurs when an earlier treatment influences measurements in a later period; a period effect is a difference associated with the time or sequence of measurement rather than the treatment itself. These are general design considerations, not findings from this trial. The washout interval, checks for carryover, and model terms used to address period or sequence are not reported in the registry record.

What can be inferred from the posted summaries?

The arm summaries and ratio estimates support a descriptive reading of the registered primary outcome. They do not allow a reader to reproduce the analysis fully. The record does not identify the statistical method, the transformation and back-transformation details, the handling of missing period measurements, or the analysis population. It also does not provide standard errors or participant-level data. Consequently, any simple calculation from arm summaries would not necessarily reproduce a crossover analysis that uses within-participant information.

General statistical context: a recalculation from summary statistics is unadjusted when it does not incorporate the trial’s full model, allocation structure, or participant-level covariance. Such a calculation can serve as a check on broad numerical consistency, but it is not a substitute for the prespecified analysis. The registry’s posted ratio estimates are the direct reported results; the detailed methods needed to independently verify them are not reported in the registry record.

Why does the analysis plan matter?

Interpretation depends not only on the estimate but also on how the outcome and analysis were specified. The record lists 24 outcome measures, 23 posted secondary outcomes, and 62 analyses. Multiple outcomes and analyses can raise questions about which results were primary, how inferential error was controlled, and whether the posted analyses followed a prespecified plan. The registry identifies the primary endpoint but does not report a complete statistical analysis plan, multiplicity procedure, or detailed protocol for selecting analysis populations.

Sample-size illustrations based on an observed effect are planning calculations, not evidence that the trial had a particular probability of detecting an effect. They do not describe the design justification used before the study began. The trial’s sample-size rationale and any planning assumptions are not reported in the registry record. The enrollment of 114 and the primary-summary counts of 111 per treatment are descriptive counts, not a substitute for a reported sample-size justification or a formal assessment of precision.

10. Analyses Reported by the Sponsor

The registry posts two geometric mean ratio analyses for the primary endpoint. The NKF-INS Glargine (G) versus EU-Lantus® comparison is 102.914, with a 90% confidence interval of 96.886 to 109.318. The US-Lantus® versus NKF-INS Glargine (G) comparison is 97.723, with a 90% confidence interval of 93.153 to 102.518. These are the reported comparison estimates, and the record labels them as equivalence analyses.

A recalculation using arm-level summaries is generally a simple, unadjusted check. In a crossover trial, the reported analysis may use within-participant information and account for the design in ways that cannot be reproduced from geometric means and coefficients of variation alone. The analysis method is not reported in the registry record, so the relationship between any such recalculation and the original model cannot be fully assessed from the record.

The discrepancy flag is false. There is therefore no recorded discrepancy requiring a conflicting recalculation to be set against the posted analysis. The registry’s own estimates remain the appropriate figures to quote as the reported results. The equivalence margins and decision rule are not reported in the registry record, so the posted estimates alone do not show whether the trial’s formal similarity criteria were met.

11. Multiplicity, Missing Data and Analysis Populations

The record lists 24 outcome measures, 23 posted secondary outcomes, and 62 analyses. The primary endpoint is M1 AUC0-12h; secondary outcomes cover other M1 concentration and AUC measures and insulin glargine concentration measures. The breadth of outcomes and analyses makes it important to know how the analysis plan distinguished primary questions from additional comparisons.

Multiplicity refers, in general, to the interpretive issue created when many statistical tests are performed. Without a prespecified approach, a reader cannot tell whether the reported confidence intervals or tests were adjusted for the number of outcomes or comparisons, or whether different analyses were treated as separate exploratory questions. The multiplicity procedure and the grouping of analyses into statistical families are not reported in the registry record. No adjustment should be assumed.

The record does not report analysis populations for the primary endpoint, such as the exact set of participants and periods included, or how participants with incomplete crossover data were handled. It also does not report the number of missing endpoint measurements, reasons for missingness, imputation methods, or sensitivity analyses. These details matter because crossover analyses can depend on which treatment periods are observed for each participant.

The primary-outcome summaries list 111 participants in each treatment group. Safety risk-group counts are 113 for US-Lantus®, 114 for NKF-INS Glargine (G), and 111 for EU-Lantus®. The record does not explain the different counts. They should not be used to infer which participants were included in a particular analysis or why counts differ.

The sample-size rationale and any prespecified precision target are not reported in the registry record. Planning illustrations based on observed effects are not observed power and do not reveal the original design calculation. Similarly, the record does not state whether interim analyses were planned or conducted. These absences limit assessment of the analysis strategy; they do not establish that a particular method was or was not used.

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 registry reports serious adverse events for the three treatment risk groups. The count with a serious adverse event was 0 of 113 for US-Lantus®, 0 of 114 for NKF-INS Glargine (G), and 0 of 111 for EU-Lantus®. Deaths were also recorded as 0 in each group. These are counts within the risk groups listed for safety, not the primary-outcome analysis counts.

General statistical context: observing no serious adverse events in a group does not establish that the underlying risk is zero. It means no events of that category were recorded among the participants counted in that group during the registry’s safety observation. The registry record does not report the observation duration for safety, the event-collection procedures, or further details about exposure time, so the counts should be read within those limits.

The record also lists other adverse events affecting 20 participants in the US-Lantus® group, 20 in the NKF-INS Glargine (G) group, and 31 in the EU-Lantus® group. These are counts of participants affected, not counts of all event episodes. The record does not provide event terms in the posted serious-event list, which is empty, and does not provide enough detail to interpret event severity, relatedness, or treatment attribution. The counts describe reported safety observations; they do not establish comparative safety conclusions.

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

The primary outcome provides a comparison of M1 exposure from 0 to 12 hours after a single dose of each treatment. The registry’s posted geometric mean ratios and 90% confidence intervals summarize the estimated comparisons between NKF-INS Glargine (G), US-Lantus®, and EU-Lantus®. They offer information about the magnitude and precision of the primary pharmacokinetic comparisons in the analyzed data.

The registry labels the two comparisons as equivalence analyses. However, the equivalence margins and formal decision rule are not reported in the registry record. An estimate near the no-difference reference, or a confidence interval that spans that reference, is not sufficient by itself to confirm equivalence. Without the prespecified bounds, readers cannot determine from the posted ratios and intervals alone whether the study met its intended statistical criterion for similarity.

The results concern a pharmacokinetic endpoint for M1 in healthy participants after single subcutaneous doses in a crossover study. They do not directly describe longer-term use, repeated dosing, outcomes in people with a health condition, or clinical outcomes. The registry lists pharmacodynamic and additional pharmacokinetic outcomes, but the primary result is specifically M1 AUC0-12h. Conclusions about outcomes beyond that endpoint are not supported by the primary estimates alone.

The record reports zero serious adverse events in each listed risk group, as well as non-serious adverse-event participant counts. Those figures describe recorded events in the groups and do not establish that an event cannot occur or that treatments have identical safety profiles. The available record does not report enough detail about safety observation duration or event attribution to support broader conclusions.

More generally, the posted results are one part of the evidence about the study question. Missing detail about the analytical model, analysis populations, handling of missing data, multiplicity, and equivalence criteria limits independent assessment. The most defensible reading is to report the estimates as posted, recognize their stated endpoint and population, and avoid extending them beyond the study’s design and reported outcomes.

14. Why This Trial Matters Statistically

This trial raises an important statistical question: how to compare pharmacokinetic profiles across three treatments when the design is a randomized crossover. A crossover allows participants to receive multiple treatments over separate periods, potentially enabling direct within-participant comparisons. That structure can be informative, but it also makes the analysis dependent on the treatment sequence, period effects, and the availability of measurements across periods.

The primary endpoint is a geometric-mean measure of M1 exposure over a specified interval, and the registry reports ratios with confidence intervals. This is a natural way to express proportional comparisons for positive pharmacokinetic measurements. It also illustrates why a point estimate alone is not enough: precision and the prespecified equivalence margins are central to deciding what a comparison supports. The margins are not reported in the registry record.

The trial also illustrates the difference between a stated design aim and a verifiable statistical conclusion. The record says the study was intended to demonstrate pharmacokinetic similarity and labels the comparisons as equivalence analyses. To assess that claim statistically, a reader needs the decision criteria and methods as well as the estimates. The model, equivalence boundaries, multiplicity approach, and analysis populations are not reported in the registry record.

Finally, the counts show why endpoint-specific denominators matter. The primary summaries list 111 participants per treatment, while the safety groups have different counts. Without an explanation of the analysis sets and missing-data handling, those figures should be kept distinct. Understanding these limits helps readers distinguish a precise description of posted results from a broader conclusion that the record does not establish.

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 registry record does not report the equivalence margins or the decision rule used to determine whether the comparisons met the intended similarity criterion. This is a central limitation for interpreting results labeled as equivalence analyses. Ratios and confidence intervals can be described, but the formal equivalence conclusion cannot be independently checked without the prespecified bounds.

The analysis method is not reported. In a crossover study, details such as participant effects, period and sequence terms, treatment effects, and treatment of incomplete sequences can influence estimates and uncertainty. The record also does not report the washout interval, the treatment sequence assignments, or checks for carryover. These are considerations for evaluating a crossover design, not evidence that a design problem occurred.

Analysis populations and missing-data methods are not reported. Although the primary summaries list 111 participants in each treatment group and the registry records 114 enrolled, the reason for the difference is not stated. The safety risk groups have counts of 113, 114, and 111, and the record does not explain how those counts relate to endpoint participation or treatment-period completion.

The trial lists 24 outcome measures and 62 analyses, but the record does not describe the multiplicity strategy or identify a complete statistical analysis plan. The sample-size rationale is also not reported. These omissions limit assessment of whether the posted analyses reflect prespecified methods and how uncertainty across multiple analyses should be interpreted.

Finally, the study population is identified as healthy participants, and the interventions are described as single subcutaneous doses over three treatment periods. The primary endpoint addresses M1 exposure over 0 to 12 hours post-dose. The record therefore does not provide evidence about settings, populations, dosing patterns, or outcomes beyond those recorded. Safety observation details and event attribution are not reported, which also limits interpretation of the adverse-event counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity Between NKF-INS Glargine (G), United States (US)-Lantus®, and European Union (EU)-Lantus® — NCT06627478.
• Registry record last updated 2026-10-23; status last verified 2026-07.
• Results first posted 2026-10-23.
• 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

This completed phase 1 study was randomized, double-blind, and used a three-period, three-treatment, six-sequence crossover design in healthy participants. The registry records 114 enrolled participants and lists single subcutaneous doses of NKF-INS Glargine (G), US-Lantus®, and EU-Lantus®.

The primary endpoint was M1 AUC0-12h, measured from 0 to 12 hours post-dose. The registry posts geometric mean ratios and 90% confidence intervals for NKF-INS Glargine (G) versus EU-Lantus® and US-Lantus® versus NKF-INS Glargine (G). It labels both as equivalence analyses, but the equivalence margins, detailed statistical method, analysis populations, and missing-data handling are not reported in the registry record.

The record lists 24 outcome measures, 23 posted secondary outcomes, and 62 analyses. Serious adverse events and deaths are recorded as 0 in each listed safety group. These findings describe the posted pharmacokinetic and safety data; the missing methods and decision criteria limit broader interpretation.