A Study of U-500 Insulin (LY041001) in Participants With Type 2 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of U-500 Insulin (LY041001) in Participants With Type 2 Diabetes (NCT02588950), a randomized phase 1 study. The primary outcome is Part A: Pharmacokinetics (PK): Time to Maximum Drug Concentration (Tmax) of U-500R.

2. Clinical Question

3. Trial Design

The registry describes NCT02588950 as a phase 1, randomized, unmasked, crossover study of U-500R in participants with type 2 diabetes. Eli Lilly and Company is listed as sponsor. Enrollment was 11. The study began on 2016-01-12, and primary completion was recorded as 2017-05-25. Its status is terminated; a reason for termination is not reported in the registry record.

The study had two parts. In Part A, participants received a single subcutaneous U-500R bolus and a bolus administered by continuous subcutaneous insulin infusion. The primary endpoint was assessed during Period 1 and Period 2 at the listed post-dose sampling times, from -0.5 through 24 hours. The endpoint population was participants who were randomized, received at least one dose, and had evaluable Part A pharmacokinetic data. The registry does not report how many participants met that evaluability definition beyond the group counts attached to the posted endpoint.

Participants completing Part A were described as continuing into Part B. That part compared twice-daily and thrice-daily subcutaneous injections at steady state over 5 to 10 days. The registry lists Part B pharmacokinetic and pharmacodynamic outcomes, including time to maximum concentration, total glucose infused, and time to maximum response. The record does not establish from the information how many participants completed both parts, or why enrollment and outcome-group counts differ across parts.

A crossover design allows comparisons across treatment periods in the same participant, which can account for stable differences between people. General statistical context: period effects, treatment sequence, and carryover can matter in crossover studies. The registry record does not report the protocol details or analysis adjustments for those considerations. It also does not report the reason the study was terminated.

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.

Period 1 (Part A)

Period 2 (Part A)

Reasons for not completing this period:

Period 3 (Part B)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least one dose of study drug and had evaluable PK data in part A.

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: All randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Part A: Pharmacokinetics (PK): Time to Maximum Drug Concentration (Tmax) of U-500R, measured over Period 1 and 2: -0.5, 0, 0.5, 1, 2, 3, 4, 6, 7, 8, 12, 16, 24 hours (h) post dose.

The primary endpoint, Tmax, is the time from dosing until the measured drug concentration reaches its maximum during the sampling period. In this study it was recorded in hours. The registry specifies measurements at scheduled times during Period 1 and Period 2, including pre-dose and post-dose samples. Tmax therefore summarizes the timing of the observed concentration peak, rather than the amount of drug present across the full sampling period.

General statistical context: Tmax is used in pharmacokinetic studies to characterize the timing of drug absorption and peak exposure. It can help describe how concentration profiles differ between administration approaches. It does not, by itself, describe total exposure, duration of action, glucose response, or a clinical benefit. Those questions require other endpoints and appropriate interpretation.

The registry reports the endpoint as a median with a full range for each Part A group. The median gives the central observed value, while the range displays the lowest and highest posted values. It also reports a mixed-model comparison as a geometric least-squares mean ratio and confidence interval. That model-based summary is not the same quantity as a ratio of the displayed medians. The record does not report the details needed to reconstruct the model from the group summaries alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: each statistical summary answers a particular question. A median describes the midpoint of observed values, a range describes their extremes, and a model-based estimate uses a specified statistical structure to summarize a contrast. These measures can differ without being mathematically inconsistent because they need not target the same quantity.

What does the median and full range describe?

The registry reports median Tmax and full range for each Part A group. The single-injection group’s median was 6.0 hours and its range was 0.5 to 8.0 hours. The CSII group’s median was 5.0 hours and its range was 0.5 to 12.0 hours. The median is resistant to the influence of unusually high or low observations compared with a mean. The full range is easy to interpret, but it is determined by only the two most extreme observed values and does not show how observations are distributed between them. Neither summary, on its own, quantifies uncertainty in a treatment contrast.

What does the mixed-model result describe?

The reported method is a mixed models analysis, and its parameter is a geometric least-squares mean ratio. The estimate is 1.46, with a 90% confidence interval from 1.08 to 1.97. A mixed model is a general approach that can represent relationships among observations, including repeated observations or participant-level structure. In crossover research, methods may account for within-participant comparisons. General statistical context: the exact meaning of a model estimate depends on the response scale, model terms, contrast direction, and assumptions. Those details are not reported in the registry record, so the ratio should be described using the registry’s stated label rather than reinterpreted as a particular number of hours.

A geometric least-squares mean is a model-adjusted summary on a multiplicative scale. A ratio compares two such summaries. General statistical context: a ratio of 1 is the equality reference; values on either side indicate a contrast on the ratio scale. The confidence interval expresses uncertainty for that model-based contrast. The posted confidence interval lies above 1, but no p-value is reported. It is not appropriate to infer additional model details or a specific adjustment strategy from the result label alone.

Why can the model estimate differ from the medians?

The group medians are unadjusted descriptive summaries, whereas the model result is reported as a geometric least-squares mean ratio. Those are different statistical quantities, potentially using different scales and accounting for the crossover structure in different ways. The registry does not report enough detail to reconstruct the analysis or identify which features account for the difference. The two summaries should therefore be presented separately rather than treated as interchangeable calculations.

What can a confidence interval tell the reader?

General statistical context: a confidence interval gives an estimate together with a measure of uncertainty under the analysis model. A narrower interval generally indicates greater precision on the scale being estimated; a wider one indicates less precision. The interval does not account automatically for every possible source of bias, missingness, or model misspecification. Here, the 90% interval is the inferential uncertainty reported for the model-based ratio. The small study enrollment and unavailable model details limit how far that precision can be generalized.

What is not established by this result?

The endpoint records time to maximum concentration, not the full concentration-time profile or a clinical outcome. Other outcomes listed include area under the concentration curve, time to maximum response, maximum concentration, and total glucose infused, but their results are not included in the record. The registry does not report a sample-size justification, a detailed statistical analysis plan, interim analyses, or a missing-data method. Those omissions prevent a full assessment of the planned analysis and its assumptions. The sample-size figures elsewhere in the page are planning illustrations rather than observed power or evidence that the study was designed to detect a particular effect.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s analysis as a mixed-model geometric least-squares mean ratio of 1.46, with a 90% confidence interval from 1.08 to 1.97. No p-value is reported. The result is distinct from the posted medians of 6.0 hours for the single-injection group and 5.0 hours for the CSII group, because the model-based ratio and the descriptive medians do not measure the contrast in the same way.

The registry record does not provide the full model specification, so the estimate cannot be recreated from the medians and ranges alone. No discrepancy is flagged between the sponsor’s analysis and a recalculation in the record. The sponsor’s inferential analysis is therefore the reported model-based result; the descriptive group summaries remain useful for understanding observed values but should not replace it. The absence of a p-value or further model details should be retained when describing the result.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures and five posted secondary outcomes. The primary outcome is Part A Tmax. The listed secondary outcomes cover pharmacokinetic and pharmacodynamic measures in Part A and Part B. Three analyses are recorded, but a multiplicity strategy is not reported in the registry record. It is therefore not clear whether or how the statistical plan accounted for evaluating multiple outcomes or comparisons.

General statistical context: when many outcomes or hypotheses are examined, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. This does not determine whether any particular finding is valid; it means that results across multiple endpoints should be interpreted with knowledge of the prespecified hierarchy or adjustment method. Such details are not reported, so no claim about multiplicity control is warranted.

The primary endpoint population is defined as randomized participants who received at least one dose and had evaluable Part A pharmacokinetic data. The endpoint groups each list 11 participants. The record does not explain the handling of participants without evaluable data, whether all randomized participants entered the analysis, or how missing observations were treated. A missing-data method is not reported in the registry record.

The registry also does not report a detailed statistical analysis plan, sample-size justification, or interim analyses. These omissions limit assessment of whether the reported analysis followed a prespecified plan and how endpoint selection was handled. The sample-size illustrations are planning exercises based on the observed effect under stated assumptions; they are not observed power and should not be read as evidence that the study had a particular probability of detecting an effect.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

For the Part A single-injection group, zero serious adverse events were reported among 11 participants at risk; for the CSII group, zero were reported among 11 at risk. In Part B, zero serious adverse events were reported among 4 participants at risk in the BID group and among 6 at risk in the TID group. No deaths were reported in any of these groups. No serious adverse event terms are listed.

The registry also reports other, non-serious adverse events for 4 of 11 participants in the single-injection group, 3 of 11 in the CSII group, 2 of 4 in the BID group, and 2 of 6 in the TID group. These are descriptive counts, and they do not establish that an event was caused by a treatment. Part A and Part B group sizes differ, so the counts should be read with their own denominators rather than compared without context.

General statistical context: observing zero serious events in a small group does not prove that the underlying risk is zero. Safety counts summarize what was recorded among participants at risk in this study; they do not quantify rare risks precisely. The registry record does not give additional serious-event terms or further detail in the information.

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

The posted primary result describes Tmax in a small phase 1 crossover study. The reported medians were 6.0 hours after the single-injection approach and 5.0 hours in the CSII group, with ranges of 0.5 to 8.0 hours and 0.5 to 12.0 hours, respectively. The model-based result was a geometric least-squares mean ratio of 1.46 with a 90% confidence interval from 1.08 to 1.97. Together, these statistics describe observed timing and a model-based contrast, but they are not interchangeable summaries.

The result does not by itself describe total drug exposure, glucose response, or clinical effectiveness. Tmax measures when the maximum concentration was observed, not how large the maximum was or how long exposure persisted. The registry lists other pharmacokinetic and pharmacodynamic outcomes, but their results are not reported in the record.

The record also does not establish how the findings generalize beyond the studied participants. Enrollment was 11, the trial was unmasked, and the status is terminated. The reason for termination is not reported. The registry does not report a detailed analysis plan, missing-data method, or sample-size justification. These limitations make it important to distinguish the reported descriptive and model-based statistics from broader claims about treatment effects.

General statistical context: a statistically estimated contrast is not automatically a measure of practical importance, and a confidence interval does not remove uncertainty about study conduct or applicability. No medical recommendation follows from these pharmacokinetic results. They answer a narrow question about the timing of maximum measured concentration under the study’s Part A comparison.

14. Why This Trial Matters Statistically

This trial is statistically interesting because it places a pharmacokinetic comparison in a randomized crossover design. General statistical context: crossover studies can make within-participant comparisons informative when each participant experiences more than one treatment. That structure can reduce the influence of stable differences between participants, but it also makes period, sequence, and carryover considerations relevant. The registry record does not report how those design features were handled analytically.

The endpoint also illustrates why descriptive and inferential summaries need to be distinguished. The medians and ranges describe observed Tmax values, while the sponsor’s mixed-model result is a geometric least-squares mean ratio with a confidence interval. The model estimate should not be converted into an hours difference using the displayed medians. Recognizing the estimand and scale is central to reading clinical trial results accurately.

The registry includes both pharmacokinetic and pharmacodynamic outcomes across two parts, but only a limited set of numerical results is reported in the record. That makes multiplicity planning and transparent reporting important questions, while the missing analysis details limit answers. The safety counts also show why denominators matter: Part A and Part B groups differ in size, and zero serious events in a small group is not evidence of zero underlying risk.

The record therefore supports a focused statistical reading of an early-phase study, rather than broad conclusions. It offers an example of the difference between a measured concentration-timing endpoint and clinical outcomes, and of the care needed when a model-based contrast accompanies simple group summaries.

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 enrollment was 11, and the primary endpoint was limited to participants who were randomized, received at least one dose, and had evaluable Part A pharmacokinetic data. The endpoint group counts are 11 in each listed Part A group, but the registry record does not explain participant flow or provide additional information about exclusions and missing observations.

The study is marked terminated, and the reason is not reported in the registry record. The record also does not report a detailed protocol, sample-size justification, interim analyses, full statistical analysis plan, or missing-data method. It does not provide the model terms or other details needed to reproduce the mixed-model estimate. Accordingly, the model-based ratio should be reported as stated, without assigning it a more specific interpretation than the record supports.

The trial was unmasked and crossover. General statistical context: lack of masking may affect study conduct or outcome assessment depending on the procedures, while crossover analyses can be sensitive to period and carryover effects. The registry record does not explain whether safeguards or specific model adjustments addressed these issues. This is an information limitation, not evidence that a particular bias occurred.

The posted primary endpoint concerns Tmax, not a clinical outcome. Results for other listed outcomes are not reported in the record. Safety group sizes vary between parts, and the small denominators limit the precision of safety descriptions. Finally, the available summaries cannot establish how representative the study population was or whether the findings apply beyond this study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of U-500 Insulin (LY041001) in Participants With Type 2 Diabetes — NCT02588950.
• Registry record last updated 2023-10-23; status last verified 2023-10.
• Results first posted 2023-10-18.
• 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

NCT02588950 is a phase 1 randomized, unmasked crossover study sponsored by Eli Lilly and Company. It enrolled 11 participants and is listed as terminated. The primary endpoint was Part A U-500R Tmax, reported as a median and full range for a single subcutaneous bolus group and a CSII group.

The medians were 6.0 hours and 5.0 hours, respectively. The reported mixed-model geometric least-squares mean ratio was 1.46, with a 90% confidence interval from 1.08 to 1.97; a p-value is not reported. The record also describes Part B twice-daily and thrice-daily dosing and lists further pharmacokinetic and pharmacodynamic outcomes. The reason for termination, detailed analysis plan, sample-size justification, and missing-data method are not reported in the registry record.