A Study of LY2140023 in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY2140023 in Healthy Participants (NCT01637142), a non-randomized phase 1 study. The primary outcome is Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 1.

2. Clinical Question

The study was designed to assess the extent and rate of absorption of LY2140023 in healthy participants. It also describes pharmacokinetic exposure to LY2140023, its active metabolite LY404039, and radiolabeled forms of the compounds. The primary endpoint concerns exposure during Treatment Period 1, when participants received oral LY2140023 followed by an intravenous tracer infusion of radiolabeled LY2140023.

The crossover structure means that the record describes participants receiving treatments in two periods, rather than a randomized comparison of separate treatment groups. In Period 2, oral LY2140023 was followed by an intravenous tracer infusion of radiolabeled LY404039. The stated purpose and treatment descriptions identify what was administered; they do not establish the size or precision of any pharmacokinetic effect. Endpoint estimates are not reported in the registry record.

3. Trial Design

This completed phase 1 study used a nonrandomized crossover design and had no masking. Its stated enrollment was 18 healthy participants. The study began and reached primary completion in 2012-07. The sponsor listed in the registry record is Denovo Biopharma LLC.

The record describes two treatment periods. In Treatment Period 1, participants received a single oral dose of 80 mg LY2140023, followed by a 2-hour intravenous infusion of approximately 100 µg LY2140023 containing approximately 100 nCi radiolabeled LY2140023. In Treatment Period 2, participants received oral 80 mg LY2140023 followed by a 2-hour intravenous infusion of approximately 100 µg LY404039 containing approximately 100 nCi radiolabeled LY404039. The record states that there was at least a 3-day washout between doses.

Because allocation was nonrandomized, the periods should not be read as randomized treatment arms with a like-for-like control comparison. The treatment sequences differ in the intravenous compound, while both include oral LY2140023. The record does not report whether treatment order was counterbalanced or how period effects were addressed statistically. Those design details should not be assumed from the crossover label alone.

The study is pharmacokinetic in focus. The primary endpoint is an exposure measure for Treatment Period 1, and its specified analysis population includes participants with evaluable pharmacokinetic concentration data after the stated treatment. The registry record does not report pharmacokinetic endpoint estimates or a statistical analysis plan. Its design description therefore establishes the treatments and intended measurement, but not what quantitative conclusions can be drawn about exposure.

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.

Treatment Period 1

Washout Period (at Least 3 Days)

Reasons for not completing this period:

Treatment Period 2

Analysis population for the primary outcome, as defined in the registry: Participants who received oral LY2140023 with IV \[14C\]-LY2140023 and had evaluable pharmacokinetic (PK) concentration data.

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 participants who received at last 1 dose of LY2140023.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY2140023 and LY404039 in Treatment Period 1, measured over Predose and 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16 and 24 hours postdose.

The primary endpoint is the area under the concentration-versus-time curve from time zero extrapolated to infinity, abbreviated AUC[0-inf], for LY2140023 and LY404039 in Treatment Period 1. The registry record describes exposure for the parent compound, the active metabolite, and radiolabeled LY2140023 and LY404039. Concentrations were scheduled for measurement predose and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16 and 24 hours postdose. The unit is nanograms times hours per milliliter.

In general, an area under a concentration-time curve represents cumulative measured drug exposure over the interval covered by the curve. Extrapolation to infinity extends the estimate beyond the last measured time point, based on the concentration-time profile. The endpoint is useful in pharmacokinetic studies because it condenses observations across time into an exposure measure, rather than relying on a single concentration measurement. The extrapolated portion can contribute uncertainty, especially when the observed sampling profile provides limited information about the later decline in concentration.

The record specifies a geometric mean as the summary parameter and a geometric coefficient of variation as the dispersion measure. In general, geometric summaries are used for positive measurements that may be unevenly distributed on the original scale. The registry record gives the endpoint definition but does not report its estimates, dispersion values, or confidence intervals.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a geometric mean as the primary endpoint summary and a geometric coefficient of variation as its dispersion measure. It does not provide the analysis details or endpoint results needed to reproduce or evaluate a statistical comparison. The discussion below explains the named statistical concepts in general and distinguishes those concepts from the methods actually documented for this study.

What does AUC[0-inf] represent?

In general, AUC is the area under a concentration-versus-time profile. It combines information across multiple sampling times, so it reflects exposure over an interval rather than a concentration at one moment. AUC[0-inf] denotes an estimate extending from time zero to infinity. Since concentrations are sampled only at scheduled times, the tail beyond the last observation is estimated rather than directly observed. The approach used to estimate that tail is not reported in the registry record.

The listed sampling schedule runs from predose through 24 hours postdose, with measurements at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 12, 16 and 24 hours after dosing. In general, the timing and completeness of concentration measurements affect how well the observed profile characterizes exposure. The endpoint definition alone does not indicate how missing measurements or unusual concentration profiles were handled.

Why use a geometric mean?

In general, pharmacokinetic measurements are positive and can have a right-skewed distribution, with some values substantially larger than others. A geometric mean summarizes values on a multiplicative scale and is commonly used when analysis is conducted after logarithmic transformation. The registry record names the geometric mean but does not state whether values were transformed for analysis, how the summary was calculated, or whether adjustments were used.

A geometric coefficient of variation describes relative spread around a geometric summary. In general, it can help convey how much individual measurements vary relative to the central value. It is not a confidence interval and does not by itself quantify the precision of an estimated group mean. No numerical geometric coefficient of variation is reported for this endpoint.

What does a crossover design imply?

In a crossover study, participants receive treatments in different periods, allowing measurements from one participant to be considered across treatment conditions. In general, this can help account for stable differences between participants when a suitable within-participant comparison is planned. It also makes period, sequence, and carryover effects relevant considerations. The registry record describes a nonrandomized crossover and a washout of at least a 3-day interval between doses, but it does not report how period or sequence effects were analyzed or whether carryover was assessed.

The two periods do not constitute a randomized, like-for-like control comparison according to the registry record. Both include oral LY2140023, but their intravenous tracer compounds differ. The record does not specify a formal contrast between periods or identify an analysis model for such a contrast. It would therefore be inappropriate to infer a standard crossover treatment-effect estimate from the design description alone.

What can be said about uncertainty and testing?

In general, a confidence interval presents a range of values compatible with an estimate under a specified statistical method. Its width depends on factors including variability, sample information, and the analysis model. A p-value is a measure related to how compatible data are with a stated null hypothesis and model; it does not provide the magnitude of an effect. The registry record does not report confidence intervals or p-values for the primary endpoint, nor does it specify a formal hypothesis test.

General sample-size illustrations are planning calculations, not observations from the trial. The described illustration uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Any such calculation is a hypothetical planning exercise; it is not observed power and does not establish how the study was originally designed. The original sample-size justification is not reported in the registry record.

General methods may also need to account for over-dispersion, meaning that variability is greater than a model assumes. When that occurs, standard errors or uncertainty estimates based on the narrower variance assumption can be too small. No model details are reported for this study, so it is not possible to determine whether over-dispersion was relevant or how variability was modeled. The registry entry does not report an interim analysis or a detailed statistical analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures, while the primary outcome described in detail is the pharmacokinetic AUC[0-inf] endpoint for Treatment Period 1. The details of the other outcome measure are not reported in the registry record. The record also does not describe a multiplicity adjustment, a hierarchy among multiple endpoints, or a plan for controlling the chance of false-positive findings across analyses. Such procedures should not be inferred merely from the presence of more than one outcome measure.

Missing-data procedures are not reported in the registry record. This is relevant to the primary endpoint because its stated population is participants who received oral LY2140023 with intravenous radiolabeled LY2140023 and had evaluable pharmacokinetic concentration data. The definition identifies an analysis population, but does not say how evaluability was determined, how incomplete concentration profiles were handled, or whether any missing values were imputed. The number contributing evaluable data is also not reported in the registry record.

The registry record does not provide a statistical analysis plan, identify a prespecified model, or state whether analyses were adjusted for period or sequence. It does not report formal inferential analyses for the primary endpoint. These omissions limit interpretation of how endpoint estimates would have been generated and how uncertainty or multiple analyses were addressed. They do not establish that a particular procedure was or was not used outside what is recorded in the registry.

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 record lists serious adverse events for two treatment groups. For oral 80 mg LY2140023 with intravenous LY2140023 and radiolabeled LY2140023, 18 participants were at risk and 0 were listed as affected by serious adverse events. For oral 80 mg LY2140023 with intravenous LY404039 and radiolabeled LY404039, 17 were at risk and 0 were listed as affected. No serious adverse event terms are listed.

Other adverse events are listed for 8 participants in the first group and 10 in the second; the corresponding numbers at risk are 18 and 17. These are registry counts, not estimates of comparative risk. The treatment groups represent periods in a nonrandomized crossover study, so their counts should not be interpreted as results from independent, randomized parallel arms. The record does not report whether events were considered related to study treatment, their severity, or their timing.

Death counts are not reported in the registry record. Zero listed participants affected by serious adverse events should not be rephrased as evidence that no deaths occurred, because the death information is absent. Adverse event counts also do not establish that a treatment caused an event or that the treatments differ in safety.

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

This record documents a completed phase 1 pharmacokinetic study in healthy participants. It describes two treatment periods involving oral LY2140023 and intravenous tracer infusions of either radiolabeled LY2140023 or radiolabeled LY404039. It also defines a primary exposure endpoint and the population intended for that endpoint. These details clarify the study’s objective and structure.

The registry record does not report the primary endpoint values or their dispersion. It therefore does not establish the observed exposure magnitude, the variability among participants, or the precision of the endpoint estimates. No formal inferential results are reported, so the record does not support claims about statistical significance or a quantified difference between periods.

The study’s nonrandomized crossover design also limits how the treatment descriptions can be interpreted. The periods differ in the intravenous tracer compound and are not designated as a like-for-like randomized control comparison. Without a reported statistical contrast and its uncertainty, the treatment-period descriptions alone cannot establish a comparative effect.

The adverse-event entries provide counts of participants affected, alongside the numbers at risk for each treatment group. They are descriptive registry data. They do not show that an event was caused by treatment, and the registry record does not report death counts.

Any planning illustration based on an observed effect is a hypothetical sample-size calculation, not an observed measure of power. In general, observed power is not a substitute for reporting an effect estimate and its uncertainty. The original sample-size justification and detailed statistical plan are not reported in the registry record. Overall, the entry describes what was intended and which safety counts were recorded, but does not provide the quantitative endpoint findings needed for a fuller assessment of pharmacokinetic magnitude or precision.

13. Why This Trial Matters Statistically

This study illustrates how pharmacokinetic questions can require measurements across time and across related compounds. AUC[0-inf] is intended to represent cumulative exposure, while the scheduled concentration measurements provide the observations used to characterize the concentration-time profile. Naming the endpoint and sampling schedule helps readers understand the measurement target, even when the endpoint results are not reported.

The crossover structure also highlights why design labels need to be read alongside treatment descriptions. Although both periods include oral LY2140023, the intravenous tracer compound differs between them. The registry record classifies allocation as nonrandomized and cautions that the arms are not a like-for-like control comparison. A period-by-period description is therefore not equivalent to a randomized comparison of independent treatment groups.

The endpoint population is defined by evaluable pharmacokinetic concentration data. This draws attention to an important distinction between enrollment and the participants who can contribute to an endpoint analysis. The record does not give the number with evaluable primary endpoint data, nor does it describe how missing measurements were handled. These details matter for understanding the basis of an estimate.

Finally, the record demonstrates the difference between a completed study and a fully interpretable results record. Completion and treatment descriptions do not supply endpoint estimates, uncertainty intervals, or a statistical analysis plan. The adverse-event counts provide some descriptive safety information, but not comparative causal evidence. For statistical interpretation, the design, analysis population, effect estimates, and uncertainty all contribute; the registry record documents some of these elements and leaves others unreported.

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 for statistical interpretation is that the registry record does not report numerical results for the primary AUC[0-inf] endpoint. Geometric means, geometric coefficients of variation, and confidence intervals are not reported. Consequently, neither the magnitude nor the precision of pharmacokinetic exposure can be assessed from this record.

The record describes the endpoint population as participants with evaluable pharmacokinetic concentration data, but does not report how many met that definition. It does not explain how incomplete concentration profiles were handled, whether observations were excluded, or whether missing data were imputed. The method used to estimate the portion of AUC beyond the last measured concentration is also not reported.

The study is nonrandomized, and the treatment periods differ in the intravenous tracer compound. The record explicitly cautions against treating the arms as a like-for-like control comparison. It does not report an analysis addressing period, sequence, or carryover effects, nor does it specify a formal comparison between periods.

A statistical analysis plan, multiplicity procedure, and original sample-size justification are not reported in the registry record. The detailed results for the other listed outcome measure are also not reported. Safety entries are descriptive, and the record does not report event severity, relatedness, timing, or death counts. These limitations concern what the registry record makes available and do not establish what analyses may have been conducted elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of LY2140023 in Healthy Participants — NCT01637142.
• Registry record last updated 2021-09-21; status last verified 2012-08.
• Results first posted 2021-09-21.
• 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.

18. Record Summary

NCT01637142 is a completed phase 1, nonrandomized, unmasked crossover study of LY2140023 in healthy participants. The registry record lists an enrollment of 18 and describes two treatment periods separated by at least a 3-day washout. Both periods included oral 80 mg LY2140023; the intravenous tracer infusion used radiolabeled LY2140023 in Period 1 and radiolabeled LY404039 in Period 2.

The primary outcome is AUC[0-inf] for LY2140023 and LY404039 in Treatment Period 1, summarized as a geometric mean with geometric coefficient of variation. The endpoint results and formal inferential analyses are not reported in the registry record. Serious adverse events are listed for 0 affected participants in each treatment group; other adverse events are listed for 8 and 10 participants, respectively. Death counts are not reported.