Study of LY3039478 in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of LY3039478 in Healthy Participants (NCT02906618), a non-randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) From Time Zero to the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of LY3039478 and 13C 15N 2H-LY3039478.

2. Clinical Question

The study is titled “Study of LY3039478 in Healthy Participants,” and its official title describes an absolute bioavailability study using the intravenous tracer method. Its stated research questions also include how long the body takes to remove the drug and the safety of LY3039478. The primary endpoint is a pharmacokinetic measure: it characterizes drug exposure over time rather than a clinical benefit or disease outcome.

The brief summary describes oral dosing followed by an intravenous infusion. The record lists both forms of the drug, but does not report numerical AUC results, a numerical estimate of absolute bioavailability, or the precision of a comparison between the oral and intravenous measurements. The study therefore sets out a way to examine exposure after oral dosing against an intravenous tracer reference; the registry information does not establish the magnitude of that comparison.

3. Trial Design

This completed Phase 1 study enrolled 12 healthy participants. The registry record gives a start date of 2016-10-04 and a primary completion date of 2016-11-11. It identifies the sponsor as Eli Lilly and Company. Participation was expected to last up to 7 weeks, including screening, a single study period, and follow-up.

The allocation is listed as non-randomized, masking as none, and the model as single group. The record describes one oral dose of LY3039478 and one intravenous dose of 13C 15N 2H-LY3039478. The brief summary says the oral dose is followed by an intravenous infusion. These features make the study different from a randomized trial in which separate groups receive competing treatments. The IV tracer is a measurement reference within the study, not a like-for-like control arm.

Because the listed allocation is non-randomized, a comparison between the two forms should not be interpreted as a randomized treatment contrast. The record does not report participant-level paired values or explain the analysis used to compare oral and intravenous exposure. The primary endpoint population is defined as all participants who received at least one dose of study drug.

The study lists five outcome measures and one analysis. The primary outcome is AUC from time zero to the last measurable concentration for LY3039478 and its labelled IV tracer. Secondary outcomes concern maximum observed concentration, time of maximum concentration, and terminal half-life. Numerical outcome estimates are not reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study drug.

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 Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) From Time Zero to the Last Time Point With a Measurable Concentration (AUC[0-tlast]) of LY3039478 and 13C 15N 2H-LY3039478, measured over Predose, 0.5, 1, 1.5, 2, 2.5, 3.5, 4, 6, 8, 12, 24, 36, 48 Hours Postdose.

The primary endpoint is the area under the concentration-versus-time curve from time zero to the last time point with a measurable concentration, abbreviated AUC[0-tlast]. It is defined for LY3039478 and 13C 15N 2H-LY3039478, with units of nangogram*hour/milliliter (ng*h/mL). Concentration measurements are specified at predose and at 0.5, 1, 1.5, 2, 2.5, 3.5, 4, 6, 8, 12, 24, 36, and 48 hours postdose.

AUC is used in pharmacokinetics to describe cumulative drug exposure across the observed concentration-time profile. Using an IV tracer as a reference can help address how much of an orally administered drug reaches the bloodstream, which is the bioavailability question named in the official study title. The endpoint is limited to the period ending at the last measurable concentration; it is not the same as exposure extrapolated over an entire lifetime or treatment course.

The registry specifies the geometric mean as the summary parameter and the geometric coefficient of variation as the dispersion measure. A geometric mean summarizes positive, often right-skewed measurements on a multiplicative scale. The geometric coefficient of variation describes relative variability on that scale; it is not a confidence interval and does not itself indicate the precision of the estimated mean. The record does not give the observed geometric means, geometric coefficients of variation, confidence intervals, or a numerical oral-to-IV comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes pharmacokinetic outcomes rather than a clinical efficacy endpoint. Pharmacokinetics studies the course of drug concentrations in the body over time. The primary measure, AUC[0-tlast], combines concentration and time from dosing through the last measured time at which concentration remains measurable. Larger AUC values represent greater measured exposure over that observation window, but the registry record gives no AUC values to compare.

Why use an intravenous tracer?

General: an intravenous dose enters the circulation directly, while an oral dose must be absorbed before it reaches the circulation. A labelled tracer can be distinguished analytically from the unlabelled drug, allowing measurements from the two forms to be considered in the same pharmacokinetic study. Comparing exposure from oral dosing with exposure from the IV reference is a way to investigate absolute bioavailability. This explanation describes the general rationale for the method; it does not establish the exact laboratory or analytical procedures used in this study. Those details are not reported in the registry record.

What does the geometric mean describe?

The record specifies geometric means for the primary outcome. General: the geometric mean is calculated on a multiplicative scale and is commonly used for positive measurements whose variation is more naturally expressed in relative rather than additive terms. For example, differences between measurements may be considered as proportional changes rather than fixed increments. A geometric mean is not interchangeable with an arithmetic mean, and the two can differ when values are skewed. The registry record gives no observed geometric means for this endpoint.

What does the geometric coefficient of variation describe?

The specified dispersion measure is the geometric coefficient of variation. General: this expresses variability relative to the scale of the measurements and is useful when variation grows with the level of the measurement. It describes dispersion, not uncertainty in the estimated mean. A confidence interval is a separate quantity used to express uncertainty around an estimate under a statistical model. No confidence interval for the primary endpoint is reported in the registry record, so the precision of the endpoint estimates cannot be judged from the listed summary method alone.

What can the concentration schedule tell us?

The endpoint timeframe lists predose and measurements at 0.5, 1, 1.5, 2, 2.5, 3.5, 4, 6, 8, 12, 24, 36, and 48 hours postdose. General: collecting concentrations over time allows a concentration-time profile to be described and supports calculation of measures such as AUC, maximum observed concentration, time of maximum concentration, and terminal half-life. The listed schedule tells readers when measurements were planned or specified, but not the concentrations observed, whether every measurement was available for every participant, or how values below a measurable threshold were handled. Those analysis details are not reported in the registry record.

Why do design features matter?

The study is listed as non-randomized, unmasked, and single group. General: randomization is commonly used to balance known and unknown factors between separate treatment groups, while masking can reduce some forms of bias in outcome assessment. Neither feature is listed for this study. However, the design is a tracer-based pharmacokinetic investigation and the IV tracer is not presented as a separate control arm. The usual interpretation of a randomized, parallel-group treatment contrast therefore does not apply. The record does not describe a detailed statistical model, adjustment variables, or a formal comparison method.

The record lists one analysis and five outcome measures, including the primary AUC measure and secondary pharmacokinetic measures. It does not report whether a formal multiplicity procedure was used. Any numerical sample-size illustrations associated with a registry analysis are planning calculations, not observed power: a planning illustration asks what size might be needed under stated assumptions, while observed power is not a substitute for interpreting an estimate and its uncertainty. The registry record does not report a trial-specific sample-size justification or detailed analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including the primary AUC[0-tlast] endpoint and secondary pharmacokinetic outcomes for maximum observed concentration, time of maximum concentration, and terminal half-life. Considering several outcomes can raise multiplicity questions because repeated statistical testing may increase the chance of at least one apparently notable result. The registry record does not report whether multiplicity was addressed, whether the secondary outcomes were considered confirmatory or exploratory, or what testing hierarchy was used. No numerical endpoint results or p-values are reported in the registry record, so the impact of any multiplicity approach cannot be assessed.

The primary endpoint population is described as all participants who received at least one dose of study drug. The registry enrollment is 12, but it does not report the number included in each pharmacokinetic analysis, the number with complete concentration profiles, or whether all enrolled participants received both study forms. It also does not describe exclusions from the analysis population.

Missing-data handling is not reported in the registry record. In a concentration-time study, missing or unmeasurable samples may affect the observed profile and the calculation of derived measures. General: the consequences depend on why measurements are missing, when they are missing, and the analysis rules applied. The registry record does not specify rules for values below the limit of quantification, missing time points, or incomplete profiles. It also does not report sensitivity analyses or a detailed statistical analysis plan. These omissions limit assessment of how robust the endpoint estimates would be to incomplete data.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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

The registry lists 12 participants at risk for serious adverse events and reports 0 participants affected. It lists 12 participants at risk for other adverse events and reports 2 participants affected. These are participant counts in the safety summary; the record does not provide the specific terms for the other adverse events. No serious adverse-event terms are listed. The death count is not reported in the registry record.

The serious and other adverse-event categories should be read separately. A count of participants affected is not necessarily a count of individual events, since one participant can experience more than one event. The record does not provide event-level details, timing, severity beyond the serious/non-serious grouping, relationship to study drug, or information about how events were collected. It also does not give a breakdown by oral and IV administration.

These figures describe the adverse-event information recorded for this study; they do not establish the likelihood of an event in other populations or with other exposure durations. With 12 participants at risk, the registry summary is a limited safety description, not a broad estimate of uncommon events.

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

This study was designed to characterize LY3039478 pharmacokinetics in healthy participants using an oral dose and an isotope-labelled intravenous tracer. Its primary measure, AUC[0-tlast], is intended to describe exposure over the observed concentration period and address the study’s absolute-bioavailability question. The registry record also identifies maximum concentration, time to maximum concentration, and terminal half-life as secondary pharmacokinetic outcomes.

The record does not report numerical results for the primary or secondary pharmacokinetic endpoints. It therefore does not show the observed exposure after either administration, the size or precision of an oral-versus-IV comparison, or how long elimination took. The presence of an endpoint definition and a measurement schedule describes what was assessed, not what the measurements found. The available information also does not state how much drug reached the bloodstream after oral administration.

The safety summary records 0 participants affected by serious adverse events and 2 affected by other adverse events among 12 at risk in each category. Specific other-event terms are not reported, and the death count is not reported in the registry record. These counts do not provide event-level detail or establish safety beyond the participants and observation covered by this study.

More generally, a small, non-randomized, single-group pharmacokinetic study is not a randomized comparison of clinical outcomes. The IV tracer serves as a reference in the pharmacokinetic question rather than as an independent control group. The registry information supports describing the study’s purpose, design, endpoint definitions, and limited safety counts. It does not support claims about clinical benefit, treatment effectiveness, or the absence of risk.

13. Why This Trial Matters Statistically

This trial is statistically notable for the question it asks: how oral drug exposure compares with exposure from an intravenous tracer. A tracer-based design can address bioavailability by using an IV reference, while measuring the concentration-time profiles of both forms. That makes the endpoint definition and the distinction between a tracer reference and a separate control group central to interpretation.

The study also illustrates why endpoint summaries need to be read alongside their uncertainty and analysis details. A geometric mean and geometric coefficient of variation describe location and relative dispersion, but do not by themselves show the precision of the estimated exposure or the uncertainty in a comparison. The registry record does not give endpoint values or confidence intervals, which prevents readers from assessing the magnitude and precision of the pharmacokinetic findings.

Its non-randomized, single-group structure is another important interpretive feature. This is not a conventional parallel-group trial of competing treatments. In addition, the record names several pharmacokinetic outcomes but does not report how multiplicity was handled or how missing measurements were treated. Such details can affect how fully a reader can evaluate the reported analyses.

Finally, the safety summary is limited to counts of participants with serious and other adverse events, without event terms or a reported death count. This makes the study useful as an example of the distinction between a registered scientific question and the numerical results needed to answer it. Design details clarify what the investigators intended to measure; estimates, uncertainty, and analysis methods are needed to judge what the observed data show.

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 does not report numerical values for the primary AUC endpoint or the secondary pharmacokinetic outcomes. It also does not report confidence intervals, numerical comparisons between oral and IV exposure, or an estimate of absolute bioavailability. As a result, neither the size nor the precision of the pharmacokinetic findings can be evaluated from the registry information.

The record identifies the study as non-randomized, unmasked, and single group. It describes oral dosing followed by IV infusion, but does not report participant-level paired results or the statistical method used for a comparison. The IV tracer should not be treated as an independently randomized control arm. A detailed protocol and statistical analysis plan are not reported in the registry record.

Although the primary endpoint population is defined as participants who received at least one dose, the record does not state how many participants contributed data to each endpoint or whether there were incomplete concentration profiles. Missing-data rules, handling of concentrations below measurable limits, and sensitivity analyses are not reported. The registry also does not describe the multiplicity approach for the listed outcomes.

The safety summary gives affected-participant counts but does not list the specific other adverse events, event timing, severity details, or relationships to study drug. The death count is not reported in the registry record. Finally, the study enrolled 12 healthy participants, so these registry entries alone do not describe outcomes in other populations or establish the frequency of uncommon events.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of LY3039478 in Healthy Participants — NCT02906618.
• Registry record last updated 2025-07-09; status last verified 2025-06.
• Results first posted 2025-07-09.
• 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

NCT02906618 is a completed Phase 1 study of LY3039478 in healthy participants, sponsored by Eli Lilly and Company. It enrolled 12 participants and is listed as non-randomized, unmasked, and single group. The registry describes one oral dose of LY3039478 followed by an IV infusion of isotope-labelled LY3039478.

The primary outcome is AUC[0-tlast] for the oral drug and IV tracer, summarized using geometric means and geometric coefficients of variation. Secondary outcomes concern maximum concentration, time to maximum concentration, and terminal half-life. Numerical pharmacokinetic results are not reported in the registry record.

The safety summary reports 0 participants affected by serious adverse events and 2 affected by other adverse events among 12 at risk in each category. Specific event terms and the death count are not reported in the registry record.