This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants (NCT01825876), a non-randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞) of S-Warfarin.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01825876 |
| Phase | Phase 1 |
| Condition | Healthy Volunteers |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 17 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Healthy participants; the registry record reports enrollment of 17. The primary endpoint population was participants who received a study drug and had evaluable AUC(0-∞) data.
Intervention
Evacetrapib, described as 130 mg orally once daily for 16 days, with warfarin administered during the study.
Comparator
The registry describes a single 15 mg oral warfarin dose without evacetrapib and a regimen combining evacetrapib with warfarin. Allocation was nonrandomized, so these are not reported as like-for-like randomized comparison groups.
Primary question
What is the effect of evacetrapib exposure on the pharmacokinetics of S-warfarin, measured by its area under the concentration-versus-time curve from time zero to infinity?
The study also set out to assess warfarin pharmacodynamics. The registry summary describes measuring the time for blood to clot and comparing it with an average international normalized ratio (INR). Listed secondary outcomes include the area under the INR curve and the maximum observed INR response. These measures address a different aspect of the study question from the primary pharmacokinetic endpoint: they describe clotting-time response rather than warfarin concentration in blood.
The registry describes all participants as receiving both warfarin and evacetrapib, while the regimen descriptions distinguish a warfarin-alone dose from a dose given with evacetrapib. The participant-level order of those regimens, any washout interval, and the approach used to compare periods are not reported in the registry record. Consequently, the clinical question is clear at the level of the intended measurements, but the available record does not establish the detailed conduct needed to interpret a treatment contrast.
3. Trial Design
This was a completed Phase 1 study sponsored by Eli Lilly and Company. The registry reports a start date of 2013-04 and a primary completion date of 2013-06. It identifies the allocation as nonrandomized, masking as none, and the model as single group. Enrollment was 17, and the condition was healthy volunteers.
The regimen descriptions specify 15 mg warfarin as a single oral dose. The combined regimen specifies 130 mg evacetrapib once daily, orally, for 16 days, with 15 mg warfarin co-administered orally once on Day 10. The brief summary says the study examined warfarin with and without evacetrapib and was expected to last approximately 5 weeks, not including screening. These descriptions indicate the intended exposure conditions but do not establish the sequence each participant followed or the details of any period between regimens.
A nonrandomized, single-group study differs from a randomized parallel-group trial. In general, random allocation helps balance measured and unmeasured participant characteristics across treatment groups; the registry does not report such allocation. The labels for warfarin alone and combined treatment therefore should not be read as evidence of randomized, independent arms. The registry itself flags that the arms are not a like-for-like control comparison.
The record does not report a protocol-level explanation for the allocation, masking, or model choices, nor does it report a sample-size justification. The specific timing of the study’s primary endpoint was Days 1 and 17, with blood concentration sampling after the warfarin dose at listed time points. Whether these were separate treatment periods, and how the study accounted for within-participant measurements, is 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
| Stage | 15 mg Warfarin | 130 mg Evacetrapib + 15 mg Warfarin |
|---|---|---|
| STARTED | 17 | 0 |
| Received 1 Dose of Study Drug | 17 | 0 |
| COMPLETED | 17 | 0 |
| NOT COMPLETED | 0 | 0 |
Period 2
| Stage | 15 mg Warfarin | 130 mg Evacetrapib + 15 mg Warfarin |
|---|---|---|
| STARTED | 0 | 17 |
| Received 1 Dose of Study Drug | 0 | 17 |
| COMPLETED | 0 | 16 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | 15 mg Warfarin | 130 mg Evacetrapib + 15 mg Warfarin |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
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.
Population: All participants who received at least 1 dose of study drug.
| Characteristic | Unit | Overall Study |
|---|---|---|
| Participants analysed | 17 | |
| Age, Continuous | years | 38.2 (SD 9.4) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 16 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 13 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 4 |
| Race (NIH/OMB): White | Participants | 13 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | Participants | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞) 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.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | nanograms*hour/milliliter (ng*h/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the area under the concentration-versus-time curve from time zero to infinity (AUC0-∞) for S-warfarin, measured in nanograms*hour/milliliter (ng*h/mL). It represents the integrated concentration of S-warfarin over time, including an extrapolated portion beyond the last measured concentration. In general, an area-under-the-curve measure is used to characterize overall exposure rather than concentration at a single sampling time.
The registry specifies a geometric mean as the summary parameter and a geometric coefficient of variation as the measure of dispersion. A geometric mean is a way of summarizing positive measurements on a multiplicative scale; the coefficient of variation describes relative variability on that scale. These summaries can be useful when pharmacokinetic measurements are skewed or vary proportionally, but the registry does not report the observed endpoint value or its uncertainty.
Concentrations were scheduled for measurement on Days 1 and 17 after the warfarin dose at 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours. The listed schedule describes the intended sampling times. It does not establish that every measurement was obtained for every participant. The endpoint population was limited to participants who received a study drug and had evaluable AUC(0-∞) data; the number meeting that condition is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a pharmacokinetic primary endpoint but does not report its observed value, the size or direction of any treatment contrast, a confidence interval, or a p-value. It therefore does not support a numerical conclusion about how S-warfarin exposure differed with evacetrapib. The registry record also does not report statistical analyses, despite listing outcome measures. Without those results, the endpoint definition alone cannot establish the magnitude or precision of an association.
The study’s intended interpretation involves more than the primary concentration-based endpoint. Its stated purpose also includes evaluating warfarin therapy through clotting-time measures. Listed secondary outcomes include AUCINR and INRmax, along with AUC0-∞ and Cmax for R-warfarin. The record does not report the observed values for these secondary measures or any statistical comparisons. Thus, the presence of these outcomes in the registry identifies what was to be assessed, not what the study found.
In general, a confidence interval expresses the range of effect values compatible with the data and the analysis assumptions. Its width conveys precision: a wider interval indicates less precision than a narrower interval. No confidence interval is reported for the primary endpoint in the registry record, so the precision of any effect estimate cannot be assessed from this record.
Design also shapes interpretation. The registry classifies the study as nonrandomized and single group, and specifically notes that the arms are not a like-for-like control comparison. In general, results from such a design can be affected by differences in timing, period, or other factors that coincide with treatment exposure. The record does not provide enough detail to determine how those factors were handled. A comparison between regimen descriptions should therefore not be treated as a randomized causal estimate.
The safety counts are also descriptive rather than evidence of comparative risk. The record lists no serious adverse events among participants at risk in each displayed group, and it reports other adverse events affecting participants. The group descriptions may reflect study exposures rather than independent randomized arms. These counts do not, by themselves, provide an adjusted comparison or establish the likelihood of events in other populations.
Overall, the posted registry information documents a small healthy-participant pharmacokinetic and pharmacodynamic study, its intended measures, and some adverse-event counts. It does not report the primary or secondary outcome results needed to characterize an effect, nor the analysis details needed to judge statistical uncertainty.
9. Statistical Methods Explained
The registry describes a study intended to measure warfarin pharmacokinetics and pharmacodynamics during exposure with and without evacetrapib. The main endpoint is continuous: AUC0-∞ for S-warfarin, reported in the registry as a geometric mean with geometric coefficient of variation. The record does not provide the observed summary or the statistical model used to estimate a treatment contrast.
What does AUC measure?
Area under a concentration-versus-time curve combines concentration measurements across the sampling period into an overall exposure measure. It differs from a single concentration because it accounts for the course of measured concentrations over time. Extending the area to infinity requires estimation of the portion beyond the final observed sample. The registry states that the endpoint was assessed after warfarin dosing on Days 1 and 17, with sampling scheduled through 144 hours. It does not describe the extrapolation method or report how much of the endpoint depended on extrapolation.
The other named pharmacokinetic measures are AUC0-∞ and Cmax for R-warfarin. Cmax is the maximum observed concentration, whereas AUC describes overall exposure. AUCINR and INRmax are pharmacodynamic outcomes: they summarize the clotting-time response using INR over time or its maximum observed response. In general, pharmacokinetic measures describe drug concentration, while pharmacodynamic measures describe a measured response. Neither type of measure can be interpreted from its definition alone; observed results and their uncertainty are needed.
Why use geometric summaries?
Positive biological measurements may be more naturally summarized multiplicatively than additively. The geometric mean reflects a central value on that scale, and the geometric coefficient of variation conveys relative spread. In general, this approach can be useful when values are right-skewed or when proportional differences are more meaningful than absolute differences. It does not eliminate the need to report the underlying analysis, the number of evaluable participants, and uncertainty around the treatment contrast. Those details are not reported in the registry record.
What does over-dispersion mean in general?
Over-dispersion occurs when observed variability is greater than a statistical model expects. For count outcomes, for example, a simple model may underestimate uncertainty if events cluster more than expected. In general, ignoring over-dispersion can make intervals too narrow and tests too optimistic. The registry does not identify an over-dispersion model or a count-based primary analysis for this study. This concept is therefore background on statistical methods, not a claim about the analysis used in this trial.
How should the design affect comparisons?
Randomization is a method for assigning participants to treatment conditions by chance. In general, it reduces systematic differences between groups at baseline. This study is recorded as nonrandomized and single group, and the registry cautions that the regimen groups are not a like-for-like control comparison. If participants experienced both conditions, within-participant analysis could account for some stable individual differences, but the participant-level sequence and analysis approach are not reported. It would be inappropriate to assume a crossover analysis or a specific adjustment method without that information.
The record lists a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such planning calculations are hypothetical illustrations, not observed power and not evidence that the original study was designed to a particular power target. In general, power is a design-stage probability conditional on assumptions about effect, variability, allocation, and analysis. The stated assumptions do not replace a protocol-based sample-size justification, which is not reported in the registry record. The trial itself is single group and nonrandomized, so a hypothetical equal-allocation comparison does not describe its actual allocation.
The registry notes that time-to-event planning quantities, if used, refer to total events, while other planning quantities refer to participants per arm. The primary endpoint in this study is an AUC measure, not a time-to-event outcome. No specific sample-size illustration values or trial design justification are reported in the registry record.
What analysis information is missing?
The record does not report the primary endpoint estimate, an inferential test, a confidence interval, a transformation or model, or the handling of incomplete concentration profiles. It also does not report whether the endpoint was analyzed as a within-participant change, a ratio, or another contrast. These choices matter because they determine both the interpretation of the estimated effect and its uncertainty. The endpoint specification identifies what was to be measured, but does not fully specify how the analysis was conducted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures overall and names a primary pharmacokinetic outcome along with secondary measures. The named secondary measures include AUC0-∞ and Cmax for R-warfarin, AUCINR, and INRmax. The registry does not report a multiplicity plan describing how interpretation or error rates were handled across outcomes, time points, or analyses. It also does not report whether any outcomes were prioritized beyond the designation of the primary endpoint.
In general, testing multiple outcomes creates more opportunities for apparently notable results to arise by chance. A prespecified analysis hierarchy or adjustment can address this issue, but the appropriate approach depends on the study objectives and analysis plan. No such approach is reported in the registry record, and no statistical analyses are listed. Since outcome results are also not reported, it is not possible to assess the role of multiplicity in the findings.
The primary endpoint population is defined as participants who received a dose of study drug and had evaluable AUC(0-∞) data. The enrolled sample was 17, but the number with evaluable primary endpoint data is not reported in the registry record. The record does not describe missing-data handling, exclusions, imputation, or whether all eligible participants contributed to each secondary outcome. It also does not report a participant flow by regimen or endpoint.
These omissions limit assessment of whether outcome estimates represent the enrolled participants and whether missing measurements could have influenced results. In general, missing data can affect both precision and bias, depending on why values are absent and how the analysis handles them. No particular missingness mechanism or method can be inferred from the registry entry.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 15 mg Warfarin | 0 | 17 | 0.0% |
| 130 mg Evacetrapib | 0 | 17 | 0.0% |
| 130 mg Evacetrapib + 15 mg Warfarin | 0 | 16 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 15 mg Warfarin | 5 of 17 |
| 130 mg Evacetrapib | 2 of 17 |
| 130 mg Evacetrapib + 15 mg Warfarin | 4 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 15 mg Warfarin | 130 mg Evacetrapib | 130 mg Evacetrapib + 15 mg Warfarin |
|---|---|---|---|---|
| Vessel puncture site haemorrhage | General disorders | 2 of 17 | 0 of 17 | 2 of 16 |
| Lymphadenopathy | Blood and lymphatic system disorders | 0 of 17 | 0 of 17 | 1 of 16 |
| Constipation | Gastrointestinal disorders | 0 of 17 | 1 of 17 | 0 of 16 |
| Tooth abscess | Infections and infestations | 0 of 17 | 0 of 17 | 1 of 16 |
| Contusion | Injury, poisoning and procedural complications | 1 of 17 | 0 of 17 | 0 of 16 |
| Nail injury | Injury, poisoning and procedural complications | 0 of 17 | 1 of 17 | 0 of 16 |
| Headache | Nervous system disorders | 0 of 17 | 0 of 17 | 1 of 16 |
| Acne | Skin and subcutaneous tissue disorders | 0 of 17 | 1 of 17 | 0 of 16 |
| Ecchymosis | Skin and subcutaneous tissue disorders | 1 of 17 | 0 of 17 | 0 of 16 |
| Erythema | Skin and subcutaneous tissue disorders | 1 of 17 | 0 of 17 | 0 of 16 |
The registry lists serious adverse events affecting 0 participants among 17 at risk in the 15 mg warfarin group, 0 among 17 at risk in the 130 mg evacetrapib group, and 0 among 16 at risk in the combined 130 mg evacetrapib plus 15 mg warfarin group. These are counts for the groups as recorded, not a randomized comparative estimate. The registry does not list serious adverse-event terms.
Other adverse events affected 5 of 17 participants in the 15 mg warfarin group, 2 of 17 in the 130 mg evacetrapib group, and 4 of 16 in the combined group. These counts describe participants with events; they do not give event severity, duration, recurrence, or a statistical comparison. The groups should not be assumed to be independent or directly comparable, given the nonrandomized, single-group design and the registry’s caution about like-for-like comparison.
The death fields are not reported in the registry record. These safety figures should be read as registry counts for the recorded groups, not as a complete account of safety or as evidence about risk beyond this study population.
12. What the Result Does, and Does Not, Mean
The record establishes that the study was designed to examine warfarin exposure and clotting-time response with and without evacetrapib in healthy participants. It specifies a primary S-warfarin AUC endpoint, pharmacokinetic and pharmacodynamic secondary measures, dosing descriptions, and some adverse-event counts. It does not report the primary endpoint result, secondary outcome results, statistical analyses, or confidence intervals.
Accordingly, the record cannot show how large or precise any difference in warfarin exposure or INR response was. It also cannot establish whether any observed difference, if one was found, was attributable to evacetrapib rather than treatment order, timing, or other factors. Those concerns are particularly relevant because the study is identified as nonrandomized and single group, and the registry explicitly warns against treating the arms as like-for-like controls.
The primary endpoint is a pharmacokinetic measure, not a direct clinical outcome. The stated secondary INR measures assess a clotting-time response, but their observed values are not reported. Thus, the registry entry documents the questions and measurements planned, rather than the evidence needed to answer them.
The safety counts indicate no serious adverse events recorded in the displayed groups and report other adverse events affecting participants. They are descriptive counts in a small healthy-participant study and do not support a broad comparative safety conclusion. The registry record does not report deaths, detailed event terms, or inferential safety analyses.
In short, the study record is informative about design intent and endpoint definitions, but incomplete as a source for treatment-effect interpretation. Any conclusion about the magnitude, direction, precision, or clinical importance of an interaction would require results and analysis details not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically relevant because it illustrates how a narrowly defined pharmacokinetic question depends on both measurement and design. AUC0-∞ summarizes concentration over time, while Cmax captures a peak concentration and INR outcomes describe a measured response. These endpoints are related to the study’s aims but are not interchangeable. A report needs to identify the outcome, population, contrast, and uncertainty clearly for readers to understand what each result means.
The registry also highlights the importance of distinguishing study conditions from randomized comparison groups. It labels the study nonrandomized and single group and cautions that its arms are not like-for-like controls. In general, that distinction prevents a descriptive contrast from being mistaken for a randomized treatment effect. Knowing whether the same participants received both regimens, in what order, and under what interval is important for choosing and interpreting an analysis; those details are not reported in the registry record.
Another statistical lesson is that a prespecified endpoint does not itself provide evidence of an effect. The record identifies the primary measure and its sampling schedule, but does not report an estimate or uncertainty. Without those results, readers cannot judge precision or compare the observed data with a clinically meaningful threshold.
Finally, planning illustrations should be kept separate from observed results and original design decisions. The registry’s stated planning assumptions are hypothetical and do not document a protocol-based sample-size justification. Together, these points make the record useful for understanding the study question and reporting gaps, while limiting what can be concluded from the posted information.
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 principal limitation for interpretation is that the registry record does not report the primary endpoint estimate or its uncertainty. Secondary outcome results and statistical analyses are also not reported. Although the endpoint definitions and sampling schedule are described, there is no reported result with which to assess magnitude, direction, or precision.
The design is listed as nonrandomized and single group. The registry explicitly cautions that the arms are not a like-for-like control comparison. The participant-level sequence of regimens, any washout interval, and the method used to account for treatment period are not reported. These omissions make it impossible to determine from the registry record how the intended with-and-without-evacetrapib contrast was structured or analyzed.
The primary endpoint population requires a dose and evaluable AUC(0-∞) data, but the number of participants meeting that definition is not reported. Missing-data methods, exclusions, and endpoint-specific denominators are also not reported. This limits assessment of completeness and representativeness of the outcome data.
The record gives only limited safety summaries: counts of participants affected by serious and other adverse events. It does not list serious-event terms, and death figures are not reported. The study involved healthy volunteers and enrollment of 17, so the safety counts should be understood in that study context rather than generalized to other populations.
Finally, the registry does not report the sample-size justification or a multiplicity plan. The stated planning assumptions are illustrations, not documentation of the trial’s original design rationale. These limitations arise from information absent from the registry record and should not be filled by assuming a conventional protocol or analysis.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants — NCT01825876.
- Registry record last updated 2018-10-09; status last verified 2018-02.
- Results first posted 2018-10-09.
- 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.
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18. Record Summary
NCT01825876 is a completed Phase 1 study sponsored by Eli Lilly and Company, with 17 participants recorded as enrolled. The registry identifies healthy volunteers, nonrandomized allocation, no masking, and a single-group model. It describes warfarin given alone and evacetrapib given with warfarin.
The primary endpoint is S-warfarin AUC0-∞, summarized as a geometric mean with geometric coefficient of variation. Sampling was scheduled after warfarin dosing on Days 1 and 17. Secondary measures include R-warfarin pharmacokinetics and INR-based pharmacodynamic outcomes.
The registry reports adverse-event counts but does not report the primary endpoint result, secondary outcome results, statistical analyses, or the evaluable primary-endpoint sample size. The available record therefore describes the study question and methods more fully than its findings.