Study to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity Between NKF-INS(A), US-NovoLog®, and EU-NovoRapid®: 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(A), US-NovoLog®, and EU-NovoRapid® (NCT06492226), a randomized phase 1 study. The primary outcome is Aspart Concentration-time Curve From 0 to 12 Hours Area Under the Insulin Aspart Concentration-Time Curve (AUC0-t)..

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, double-blind, single-center, single-dose, three-period, three-treatment, six-sequence crossover study. The registry lists 54 enrolled participants and a completed status. The recorded start date is 2024-07-30, and the primary completion date is 2024-10-31. Participants were healthy male adult volunteers.

Each treatment was a single subcutaneous dose administered over three treatment periods. The three treatments were NKF-INS(A), US-NovoLog®, and EU-NovoRapid®. In a crossover design, participants receive multiple treatments in separate periods, allowing treatment responses to be compared within participants. Randomization assigns treatment order; the registry specifies six sequences but does not report their allocation details. The masking designation is double, but the roles of the masked parties are not described in the registry record.

The primary endpoint was an insulin aspart concentration-time area under the curve, described as AUC0-t and covering 0 to 12 hours. Its timeframe is day 1 for 12 hours, and its unit is min*ng/ml. The primary outcome description frames the analysis as a comparison of NKF-INS(A) with US-approved and EU-authorized insulin aspart. The registry also lists six secondary outcomes, including additional exposure and timing parameters.

The PK arm summaries report n=52 for each treatment. The safety records use at-risk counts of 53 for NKF-INS(A), 53 for EU-NovoRapid®, and 52 for US-NovoLog®. These figures describe the posted records; the registry does not explain how participants entered or were excluded from each analysis population.

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

Reasons for not completing this period:

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 Aspart Concentration-time Curve From 0 to 12 Hours Area Under the Insulin Aspart Concentration-Time Curve (AUC0-t)., measured over Day 1 for 12 Hours.

The primary endpoint measures insulin aspart exposure over time. Area under the concentration-time curve represents the accumulated concentration across the stated observation interval. In this trial, the endpoint is described as the area under the serum insulin aspart concentration-time curve from 0 to 12 hours, with a timeframe of day 1 for 12 hours and a unit of min*ng/ml. The registry labels the measure AUC0-t.

Exposure measures are used in pharmacokinetic comparisons because they describe how much drug is present in the measured biological sample over a period, rather than at only one sampling moment. In general, comparing exposure profiles can help assess whether products have similar pharmacokinetic behavior under the study conditions. The registry’s primary description identifies the question as pharmacokinetic similarity between NKF-INS(A) and the US-approved and EU-authorized insulin aspart products.

The posted arm summaries are geometric means: 895.0 for EU-NovoRapid®, 899.2 for US-NovoLog®, and 904.1 for NKF-INS(A). The reported geometric coefficients of variation are 18.43, 18.71, and 17.17, respectively. The registry’s reported pairwise comparisons express the results as geometric mean ratios with confidence intervals. The protocol’s similarity margins and the detailed statistical method are not reported in the registry record, so the endpoint values alone do not specify the formal criterion used to conclude similarity.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean ratio express?

In general, a geometric mean is useful for measurements that are positive and may vary multiplicatively. A geometric mean ratio compares the geometric mean in one treatment with that in another on a ratio scale. A ratio of 100 represents equal geometric means when the ratio is expressed as a percentage. Values on either side of 100 indicate relative differences in the compared means, but the registry record does not specify the numerator and denominator ordering for these displayed estimates. The trial’s reported ratios are 101.024 for NKF-INS(A) and EU-NovoRapid®, and 100.682 for NKF-INS(A) and US-NovoLog®.

How should the confidence intervals be read?

In general, a confidence interval expresses uncertainty around an estimate under a particular statistical model and procedure. A confidence interval is not a guarantee that the true value lies within its limits. The reported 95% interval for the EU-NovoRapid® comparison is 98.754 to 103.346; the reported 90% interval for the US-NovoLog® comparison is 98.567 to 102.843. Each interval includes 100. The registry does not give the equivalence margins, so the intervals cannot be assessed against the study’s formal similarity criterion from the registry record alone. The statistical methods used to calculate them are also not reported in the registry record.

What does the geometric coefficient of variation describe?

In general, the geometric coefficient of variation describes relative spread for measurements analyzed on a logarithmic scale. It is distinct from a confidence interval: a coefficient of variation summarizes variability in observed measurements, whereas a confidence interval describes uncertainty about an estimated quantity. The posted values are 18.43 for EU-NovoRapid®, 18.71 for US-NovoLog®, and 17.17 for NKF-INS(A). These arm-level summaries do not show the within-participant covariance or the details of the crossover comparison.

Why does the crossover structure matter?

In general, a crossover study measures participants under more than one treatment, so comparisons can use within-participant information. This can account for stable differences between participants, although period effects, sequence effects, and other design features may also matter. The study is described as randomized, double-blind, and organized into three periods, three treatments, and six sequences. The registry does not report the statistical model, treatment sequence allocation, handling of period or sequence effects, or the method for assessing carryover. Those details should not be inferred from the design label alone.

How should the planning illustrations be interpreted?

The record describes sample-size calculations as planning illustrations based on the observed effect, not as the study’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustration gives a total event count, while other outcomes use participants per arm. These calculations are not observed power and do not establish the study’s original sample-size rationale. The trial’s own sample-size justification is not reported in the registry record.

What analysis details are absent?

The registry does not name the statistical method for the reported geometric mean ratio analyses, describe the analysis populations, or state how missing observations were handled. It also does not report the equivalence margins, any interim analyses, or a prespecified multiplicity strategy. The absence of these details limits independent assessment of the analysis procedures. General statistical principles can explain what the reported measures mean, but they cannot fill in methods that are not reported in the registry record.

10. Analyses Reported by the Sponsor

The registry reports two geometric mean ratio analyses: NKF-INS(A) compared with EU-NovoRapid®, and NKF-INS(A) compared with US-NovoLog®. The posted estimates are 101.024 and 100.682, with confidence intervals of 98.754 to 103.346 at 95% and 98.567 to 102.843 at 90%, respectively. The record labels both analyses as equivalence analyses. The method field is not populated, and the equivalence margins are not reported in the registry record.

The arm-level endpoint summaries are geometric means of 895.0 for EU-NovoRapid®, 899.2 for US-NovoLog®, and 904.1 for NKF-INS(A). The registry also reports geometric coefficients of variation and n=52 for each arm. These summaries are descriptive and are not the same as the reported paired treatment comparisons.

The registry discrepancy indicator is false. No discrepancy between the posted results and the reported analyses is flagged in the record. No separate recalculated comparison values are listed in the information available for these analyses. The reported ratios and confidence intervals should therefore be read as the registry’s posted comparisons; the record does not provide enough detail to reproduce their statistical method independently.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and 24 analyses, with six secondary outcomes posted. The listed secondary outcomes include serum insulin aspart exposure measures over several intervals, early and late times to half-maximum concentration, terminal elimination half-life, and time to maximum concentration. The primary outcome is the 0-to-12-hour AUC measure. The record does not describe a hierarchy among outcomes or state whether the analyses were confirmatory or exploratory beyond the equivalence labels on the two reported primary comparisons.

Multiplicity arises when several outcomes, time points, or treatment comparisons are evaluated. In general, the more analyses that are conducted, the greater the chance that at least one result may appear unusual by chance if no adjustment or prespecified strategy is used. The registry does not report whether multiplicity was addressed, which analyses were included in any adjustment, or whether the two confidence levels reflect a prespecified testing procedure. No p-values are posted for the reported comparisons.

The primary outcome population field is blank. The record does not describe the analysis populations, such as which participants were included in each PK analysis or whether any per-protocol population was defined. It reports n=52 in each PK arm summary, while the safety at-risk counts are 53, 53, and 52. The reasons for these differing counts are not reported in the registry record.

Missing-data handling is not described. The registry does not state whether any measurements were missing, how incomplete concentration-time profiles were treated, or what rules were used for exclusions. It also does not report interim analyses or the study’s detailed statistical analysis plan. These omissions prevent a full assessment of how the listed outcomes and analyses were selected, adjusted, or handled when data were unavailable.

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 zero serious adverse events among the participants listed as at risk in each treatment group: 53 for NKF-INS(A), 53 for EU-NovoRapid®, and 52 for US-NovoLog®. Deaths are recorded as 0 in all three groups. No serious adverse event terms are listed.

These figures describe the posted safety records and the corresponding at-risk counts. They do not establish that no adverse events of any kind occurred. The record separately reports other adverse events affecting 8 participants in the NKF-INS(A) group, 6 in the EU-NovoRapid® group, and 4 in the US-NovoLog® group. The categories and event descriptions for those other adverse events are not included in the listed details.

In general, safety counts from a study describe events observed within the recorded study period and participants. They do not, on their own, determine the cause of an event or precisely characterize the frequency of uncommon events. The registry does not provide further details on severity, timing, relatedness, or the methods used to collect and classify adverse events. The small study enrollment and the healthy volunteer population also define the context in which these counts were recorded.

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

The posted results characterize pharmacokinetic exposure after single doses of NKF-INS(A), US-NovoLog®, and EU-NovoRapid® in a randomized, double-blind, three-period crossover study of healthy male adult volunteers. The primary measure is the 0-to-12-hour insulin aspart area under the concentration-time curve. The registry reports geometric mean ratios close to 100 for NKF-INS(A) compared with each reference product, with confidence intervals that include 100.

Those estimates describe the observed exposure comparisons and their statistical uncertainty. They do not, on their own, establish that a formal equivalence criterion was satisfied. That conclusion depends on prespecified equivalence margins and analysis methods, which are not reported in the registry record. The record’s equivalence labels convey the stated analysis type, but the absent margins limit independent interpretation of whether the reported intervals meet the intended criterion.

The findings are specific to the studied products, dose conditions, observation interval, and participant group. The study enrolled healthy male adult volunteers at a single center. Its primary endpoint is pharmacokinetic rather than a clinical outcome, and the registry does not provide specific pharmacodynamic results in the listed outcome details. The record therefore does not establish effects on health outcomes or describe performance in a patient population.

The safety records list zero serious adverse events and zero deaths in each group, alongside other adverse event counts. Those counts should be read as observations in this study, not as proof that serious events cannot occur. Overall, the record offers a limited account of the reported exposure comparisons and safety counts; methods, analysis populations, missing-data procedures, and the formal similarity margins are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial raises a central statistical issue in biosimilar-style pharmacokinetic comparisons: similarity is assessed through estimates and uncertainty, not by asking only whether two observed averages look close. The posted geometric mean ratios are 101.024 and 100.682, and each confidence interval includes 100. Those results describe the comparisons, but formal equivalence depends on prespecified margins and the method used to evaluate them. Because the margins and method are not reported in the registry record, readers cannot independently verify the criterion from these results alone.

The crossover design is statistically relevant because each participant receives multiple treatments across three periods. In general, within-participant comparisons can reduce the influence of stable differences among participants. At the same time, valid interpretation depends on design and analysis details, including the handling of period and sequence effects. The registry identifies randomization, double masking, three treatments, three periods, and six sequences, but does not report the analysis model or related diagnostics.

The endpoint is also important: it measures drug exposure over a specified interval rather than a clinical outcome. A precise PK estimate can answer a focused exposure question, but it does not by itself answer questions about clinical outcomes or populations not represented in the trial. The single-center healthy male volunteer setting defines the scope of the posted findings.

Finally, the record lists 10 outcome measures and 24 analyses, while the multiplicity strategy and analysis populations are not reported. This makes transparent reporting of the analysis plan especially important for judging how the stated similarity question was evaluated. The registry gives useful estimates and uncertainty intervals, but leaves methodological details needed for a complete statistical assessment unreported.

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 trial was conducted at a single center in healthy male adult volunteers. This specific population and setting limit how directly the results can be applied to other populations or settings. The study used single-dose administration, and the primary endpoint covers day 1 for 12 hours. The registry does not describe longer-term exposure or outcomes.

The central interpretation depends on the formal equivalence framework. Although both reported analyses are labeled equivalence analyses, the margins, statistical model, and detailed analysis method are not reported in the registry record. Without those details, the confidence intervals cannot be checked against the study’s intended acceptance limits. The record also does not report a statistical analysis plan, sample-size justification, or whether interim analyses were conducted.

The analysis populations and missing-data procedures are not described. PK summaries report n=52 for each treatment, while the safety records report at-risk counts of 53, 53, and 52. The record does not explain the count differences or how incomplete profiles, exclusions, or unavailable measurements were handled. It also does not report the treatment sequence allocation or the approach to period, sequence, or carryover effects.

The registry lists six secondary outcomes, 10 outcome measures, and 24 analyses, but a multiplicity strategy is not reported. Specific pharmacodynamic results are not included in the outcome details, despite the study description referring to pharmacodynamic similarity. These reporting gaps restrict independent appraisal of the full analysis and the breadth of conclusions that can be drawn from the posted record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity Between NKF-INS(A), US-NovoLog®, and EU-NovoRapid® — NCT06492226.
• Registry record last updated 2026-01-21; status last verified 2026-01.
• Results first posted 2026-01-21.
• 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

NCT06492226 is a completed phase 1 randomized, double-blind, single-center crossover study sponsored by Xentria, Inc. It enrolled 54 healthy male adult volunteers and compared single subcutaneous doses of NKF-INS(A), US-NovoLog®, and EU-NovoRapid® across three treatment periods and six sequences.

The primary endpoint was insulin aspart area under the concentration-time curve from 0 to 12 hours on day 1. PK summaries report n=52 per treatment. The registry reports geometric mean ratios of 101.024 for NKF-INS(A) versus EU-NovoRapid® and 100.682 for NKF-INS(A) versus US-NovoLog®, with 95% and 90% confidence intervals, respectively. Both intervals include 100. The equivalence margins and statistical method are not reported in the registry record.

The record lists zero serious adverse events and zero deaths in each group. Other adverse events affected 8, 6, and 4 participants, respectively. The trial status is completed; its recorded start date is 2024-07-30 and primary completion date is 2024-10-31.