Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants (NCT02161731), a non-randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of S-Warfarin.

2. Clinical Question

The study also set out to assess other aspects of warfarin exposure and pharmacodynamic response. Listed secondary measures include R-warfarin AUC and maximum concentration, the area under the INR curve, and maximum observed INR. The brief summary describes the goal of examining how much warfarin enters the bloodstream and how long it takes the body to eliminate it, alongside changes in blood-clotting time represented by INR.

The question is about drug exposure and measured clotting response in healthy participants under the stated study conditions. It is not a clinical-outcome comparison in patients receiving warfarin for prevention of blood clots. The registry record does not report the numerical results for the primary or listed secondary measures, so it does not allow a reader to judge the size or precision of any observed change.

3. Trial Design

This was a completed phase 1 study of evacetrapib and warfarin in healthy participants. The registry record describes its allocation as non-randomized, its masking as none, and its model as a single group. It reports an enrollment of 24. The study began in 2014-06 and reached primary completion in 2014-09.

The schedule describes a single oral 15 mg warfarin dose on Day 1. In the evacetrapib exposure period, participants received evacetrapib once daily by mouth for 16 days, with a single oral 15 mg warfarin dose co-administered on Day 17. The brief summary says participants received both warfarin and evacetrapib and that warfarin was assessed with and without evacetrapib. These descriptions indicate a comparison of exposure conditions within the study schedule, but the registry record does not report further details of the sequence or timing beyond the stated schedule.

Because allocation was non-randomized and the study model is listed as single group, the conditions should not be read as independent randomized treatment arms. The registry record explicitly warns that the arms are not a like-for-like control comparison. Differences between measurements could reflect the exposure condition, but the available record does not provide enough information to assess other possible explanations or to evaluate the analysis used to compare conditions.

The stated study duration was approximately 5 weeks, not including screening. The primary endpoint was S-warfarin AUC from time zero to infinity, with measurements scheduled after warfarin dosing on Days 1 and 17. Although the record names the endpoint and its analysis population, it does not report an outcome estimate, uncertainty interval, or analysis result. Details such as a protocol, statistical analysis plan, sample-size justification, or interim analysis 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.

Period 1 (Day -1 to Day 7 Predose)

Period 2 (Day 7 Dosing to Day 23)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received a dose of study drug and had evaluable data for AUC \[0-∞\].

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 From Time Zero to Infinity (AUC[0-∞]) of S-Warfarin, measured over Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose.

The primary endpoint is the area under the concentration-versus-time curve for S-warfarin from time zero to infinity, abbreviated AUC[0-∞]. It is expressed in nanogram*hour/milliliter. Concentration measurements were scheduled at 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after the warfarin dose on Days 1 and 17.

In general, an area under a concentration-time curve combines concentration measurements over time into a measure of overall drug exposure. Extending the interval to infinity represents exposure over the full profile, including the portion beyond the last observed measurement; the registry record does not describe how that portion was estimated. S-warfarin is the specific form named in the endpoint, while the secondary outcomes also include measures of R-warfarin exposure.

The endpoint is relevant to the study’s stated pharmacokinetic question: whether warfarin exposure differs when warfarin is administered with evacetrapib compared with the warfarin-only condition. The registry record specifies a geometric mean as the summary parameter and a geometric coefficient of variation as the dispersion measure. These labels describe the intended summaries, not the size or direction of a result. The numerical AUC values, the comparison estimate, and its precision are not reported in the registry record.

The primary population is defined as participants who received a dose of study drug and had evaluable AUC[0-∞] data. The record does not report how many met that definition or how unevaluable measurements were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary summary parameter as a geometric mean and the dispersion measure as a geometric coefficient of variation. It does not provide numerical summaries or describe a complete statistical analysis plan. The following concepts are general explanations of the named methods and endpoints, not claims about additional analyses performed in this study.

What does AUC measure?

In general, the area under a concentration-time curve represents overall exposure across the observation period. It combines information from concentrations measured at different times rather than focusing on a single concentration. The primary endpoint extends from time zero to infinity. The schedule lists sampling through 144 hours after warfarin dosing on Days 1 and 17, but the registry record does not explain the method for estimating exposure after the last scheduled measurement.

The study names S-warfarin for the primary endpoint and R-warfarin for two secondary pharmacokinetic outcomes. These are distinct measures in the record. A result for one should not be assumed to describe the other. The record gives no numerical AUC or maximum-concentration results for either form.

What do geometric summaries mean?

In general, a geometric mean summarizes values on a multiplicative scale, often by taking logarithms before calculating a mean and then transforming back. It can be useful for positive measurements with a skewed distribution. A geometric coefficient of variation describes relative dispersion on that scale. These summaries do not, by themselves, provide a treatment contrast or its uncertainty. The registry record does not report the actual geometric means, coefficients of variation, or a comparison estimate.

A confidence interval, in general, quantifies uncertainty around an estimate under the assumptions of the specified analysis. A p-value, in general, describes how compatible data are with a specified null model. Neither should be inferred from the endpoint’s summary-parameter label. The registry record does not report confidence intervals or p-values for the primary endpoint.

How should the schedule affect the comparison?

The record describes warfarin alone on Day 1 and warfarin with evacetrapib on Day 17 after once-daily evacetrapib dosing for 16 days. It also identifies the study as non-randomized and single group, with no masking. In general, random allocation can help balance known and unknown factors across treatment groups; this record does not describe a randomized allocation. It explicitly cautions that its arms are not a like-for-like control comparison. The available information does not specify additional design features or analytical adjustments that might affect interpretation.

For within-participant measurements, a paired analysis can account for the fact that observations from the same participant may be related. This is a general statistical concept, not a statement that a particular paired procedure was used. The analysis method for the primary comparison is not reported in the registry record.

What do the INR outcomes represent?

The registry record describes INR as a measure of blood-clotting time compared with an average. It lists area under the INR curve and maximum observed INR as pharmacodynamic measures. In general, an area-under-the-curve measure reflects the pattern over an interval, while a maximum measure captures the highest observed response. These measures answer different questions and should not be treated as interchangeable. Numerical INR results and their analyses are not reported in the registry record.

What can be inferred from the planning assumptions?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the target effect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed using those assumptions. The record does not report a sample-size justification for the study or the numerical planning estimates. Such illustrations are not observed power and should not be read as results from participants.

The assumptions refer to equal allocation between arms, whereas this study is identified as non-randomized and single group. The record itself warns that the arms are not a like-for-like control comparison. The planning assumptions therefore do not establish that the study’s actual design or analysis followed an equal-allocation model. The statistical plan and any rationale for the assumptions are not reported in the registry record.

The record lists 0 analyses. This means no analysis entries are listed in the registry information; it does not establish that no analysis was conducted outside the record. No analysis methods, hypothesis tests, adjustment procedures, or sensitivity analyses are reported in the registry record. Without those details and numerical outcomes, the reader cannot reproduce or evaluate a statistical comparison from the posted information.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary S-warfarin AUC outcome and secondary measures covering R-warfarin exposure and INR response. It reports 6 outcome measures in total, but the listed information does not give numerical results for the primary endpoint or the secondary outcomes. The record lists 0 analyses. A multiplicity procedure for handling the several outcomes is not reported in the registry record.

In general, testing several outcomes can increase the chance of at least one apparently unusual result if each is assessed separately. Statistical approaches may define a hierarchy, adjust significance thresholds, or treat some outcomes as descriptive. Which approach was intended or used in this study is not reported in the registry record. The presence of a named primary endpoint does not, by itself, establish how secondary outcomes were handled.

The primary population is defined as participants who received a study-drug dose and had evaluable AUC[0-∞] data. The record does not state how many participants had evaluable data, whether any measurements were missing, or how missing or unevaluable measurements were handled. It does not report imputation, exclusion rules beyond the stated population definition, or sensitivity analyses.

The adverse-event entries use different denominators for the combined exposure group than for the other listed groups. The registry record does not explain the reason for that difference, so it should not be interpreted as evidence of a particular missing-data process. The analysis population for each secondary outcome is also not reported in the registry record. These gaps limit assessment of whether all intended measurements and participants contributed to each outcome.

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 safety record lists three exposure groups. For 15 mg warfarin, 24 participants were at risk for serious adverse events and 0 were affected; the other-adverse-event count was also 0 among 24 at risk. For 130 mg evacetrapib, 24 were at risk for serious adverse events and 0 were affected; 2 other adverse events were reported among 24 at risk. For 15 mg warfarin plus 130 mg evacetrapib, 23 were at risk for serious adverse events and 0 were affected; the other-adverse-event count was 0 among 23 at risk.

These are descriptive counts, not estimates of comparative risk. The registry record does not report serious adverse event terms, and its list of top serious terms is empty. Death entries are null; deaths are not reported in the registry record, rather than reported as zero. The record does not give further detail about the 2 other adverse events, including their terms or severity.

Because the study is non-randomized and the record cautions that the arms are not a like-for-like control comparison, the counts should not be interpreted as a causal comparison between exposures. They describe the reported entries for the stated groups and denominators. The available safety information does not replace the unreported pharmacokinetic and INR outcome results.

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

This record describes a phase 1 study of warfarin exposure with and without evacetrapib in healthy participants. It provides the schedule, the primary endpoint definition, the intended analysis population, and several secondary measures. Those details clarify what the study set out to examine.

However, the numerical primary outcome is not reported in the registry record. The record also does not report a comparison estimate, confidence interval, p-value, or numerical results for the listed secondary outcomes. Therefore, the posted information does not establish whether warfarin exposure or INR response differed between the stated conditions, in which direction a difference might have gone, or how precisely it was estimated.

The design description also constrains interpretation. The study was non-randomized, unmasked, and listed as single group. The registry record specifically says the arms are not a like-for-like control comparison. The described schedule compares warfarin on Day 1 with warfarin given alongside evacetrapib on Day 17 after a course of evacetrapib. Without reported analysis details and results, the record cannot support a quantified treatment contrast or a causal claim.

The population was healthy participants, and the stated objectives concern pharmacokinetic and pharmacodynamic measures. The record does not describe clinical outcomes in patients receiving warfarin to prevent blood clots. Its stated aims should not be extended beyond those measured questions.

Safety entries report no serious adverse events in the listed groups and 2 other adverse events in the evacetrapib group. Those counts are limited descriptive information; death data and event details are not reported in the registry record. They do not resolve the unanswered pharmacokinetic or INR questions. In short, this registry information documents the study’s intended assessment and selected safety counts, but does not provide the outcome evidence needed to characterize the observed effect.

13. Why This Trial Matters Statistically

This study illustrates why a registry record’s endpoint definition and its outcome results must be distinguished. A clearly named measure such as S-warfarin AUC[0-∞] identifies the quantity of interest, its units, the scheduled sampling times, and the stated population. It does not reveal the observed value or the estimated comparison. Here, the numerical result and analysis are not reported in the registry record.

The design description is also important for statistical reading. A non-randomized, single-group study can raise different interpretive questions from a randomized comparison. The record explicitly warns that the arms are not a like-for-like control comparison. A reader therefore should not treat the exposure conditions as though they were randomized parallel groups, or assume that unreported methods address possible sources of difference between the Day 1 and Day 17 measurements.

The study also names both pharmacokinetic and pharmacodynamic measures. Exposure measures such as AUC and Cmax describe aspects of drug concentration; INR curve area and maximum INR describe aspects of measured clotting response. They are related to the study’s aims but represent distinct outcomes. The absence of numerical results for these measures prevents assessment of their magnitude, variability, or alignment.

Finally, the record offers a useful reminder that safety counts and efficacy-related measurements answer different questions. Descriptive adverse-event entries cannot stand in for absent pharmacokinetic or INR analyses. Statistical interpretation depends on the estimate, its uncertainty, the analysis population, and the methods used; those elements are not reported for the primary comparison.

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 of the available record is that it does not report the numerical primary endpoint result or an analysis of that endpoint. The listed secondary outcomes likewise have no numerical results in the registry record. This prevents assessment of effect direction, magnitude, and precision.

The design is non-randomized, unmasked, and identified as single group. The registry record cautions that the arms are not a like-for-like control comparison. Although the schedule describes warfarin in the absence of evacetrapib on Day 1 and with evacetrapib on Day 17, the record does not report further details about order, potential period effects, or the analysis used to compare the conditions. These design and reporting constraints limit interpretation of any contrast.

The primary analysis population is defined by receipt of a study-drug dose and evaluable AUC data, but the number meeting that definition is not reported in the registry record. Missing-data handling, exclusions, and sensitivity analyses are also not reported. The record does not state how the AUC beyond the final scheduled measurement was estimated.

The record lists 6 outcome measures and 0 analyses, but does not report a multiplicity strategy or statistical plan. It describes planning assumptions without reporting numerical planning estimates or a trial-specific sample-size justification. The safety record supplies counts but no serious-event terms; it reports 2 other adverse events in one listed group without event descriptions. Death entries are not reported as numerical values. These gaps mean the record supports only a limited description of the study’s objectives, schedule, and recorded safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants — NCT02161731.
• Registry record last updated 2018-10-03; status last verified 2018-02.
• Results first posted 2018-10-03.
• 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

NCT02161731 is a completed phase 1 study sponsored by Eli Lilly and Company. It enrolled 24 healthy participants and examined warfarin pharmacokinetics and INR response with and without evacetrapib. The record describes non-randomized allocation, no masking, and a single-group model.

The primary endpoint was S-warfarin AUC from time zero to infinity, summarized by geometric mean with geometric coefficient of variation as the dispersion measure. The registry record does not report the numerical endpoint result or its analysis. It also lists R-warfarin exposure and INR outcomes, without numerical results.

Safety entries report 0 serious adverse events in each listed group and 2 other adverse events in the 130 mg evacetrapib group. Deaths are not reported in the registry record. The record cautions that the exposure groups are not a like-for-like control comparison.