A Study of Different Particle Sizes of Evacetrapib in Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Different Particle Sizes of Evacetrapib in Healthy Participants (NCT02497391), a randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Evacetrapib.

2. Clinical Question

3. Trial Design

This completed Phase 1 study enrolled 95 healthy participants. It was randomized, unmasked, and used a crossover model. Each participant was intended to receive three single doses: one each of the Evacetrapib Reference tablet, Test 1 tablet, and Test 2 tablet, all at 130 mg, over three study periods. The tablets differed in particle size; the particle-size specifications are not reported in the registry record.

The crossover structure means that the treatment conditions were administered across periods to participants, rather than assigning participants to a single treatment arm for the whole study. This can allow comparisons within the same participant, although the registry does not describe the treatment sequences, the randomization scheme, or the statistical handling of within-participant comparisons. Details such as washout duration and other period-specific procedures are not reported in the registry record.

For each study period, the study description specifies an inpatient stay covering the day before dosing, dosing day, and the day after dosing, followed by daily outpatient visits through Day 8. The stated overall duration was about 7 weeks from first dose to study end. Screening was to occur within 28 days before the first dose, with follow-up 21 days after the last dose. The study began in 2015-07, reached primary completion in 2015-11, and is recorded as completed.

The reported primary pharmacokinetic population included participants who received at least one dose and had evaluable pharmacokinetic data. The number with a reported maximum concentration differs by treatment: 84 for the reference, 81 for Test 1, and 85 for Test 2. These are treatment-specific counts; the registry record does not explain the reasons for the differing counts. Masking was recorded as none. The methods and procedures used to maintain participant safety or manage potential bias beyond the stated design features 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.

Before assignment: Participants were randomized to 1 of 6 treatment sequences in a crossover design with 3 treatments; reference, test 1 and test 2. There was a washout period of ≥14 days between each dose. Participants were dosed 3 times during the entire study in periods 1, 2 and 3.

Period 1 (14 Days)

Period 2 (14 Days)

Reasons for not completing this period:

Period 3 (14 Days)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of study drug and had evaluable PK 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.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Evacetrapib, measured over Predose on Day 1,and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 Hours Postdose.

The primary endpoint is the maximum observed concentration, or Cmax, of evacetrapib in blood after dosing. It is reported in nanograms per milliliter (ng/mL), using a geometric mean and geometric coefficient of variation for each tablet formulation. The assessment schedule included predose on Day 1 and measurements from 0.25 through 168 hours after dosing, at the time points listed in the registry record.

Cmax is used in pharmacokinetic studies to describe the highest measured concentration reached after a dose. In a formulation comparison, concentration profiles can help characterize whether changing tablet properties is associated with different drug exposure patterns. The endpoint is a measurement of concentration, not a direct measure of clinical benefit or harm.

In general, a geometric mean is suited to positive measurements that may be skewed, because it summarizes values on a multiplicative scale. A geometric coefficient of variation describes relative spread on that scale. Neither measure alone establishes whether two formulations meet a prespecified bioequivalence criterion. Such a conclusion requires an appropriate comparison and decision rule; those results and criteria are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous pharmacokinetic measurement: maximum observed concentration of evacetrapib. The registry summarizes it with a geometric mean and a geometric coefficient of variation. These are descriptive statistics, not treatment-effect estimates by themselves. The posted values are 983 ng/mL for the reference, 1170 ng/mL for Test 1, and 1120 ng/mL for Test 2; the associated geometric coefficients of variation are 78.0, 56.0, and 66.0. These summaries use the treatment-specific populations recorded as 84, 81, and 85 participants.

General explanation: Concentration measurements are positive and can have a right-skewed distribution, with some observations substantially larger than others. A geometric mean summarizes measurements after working on a logarithmic scale and then returning to the original scale. This can be useful when proportional rather than absolute differences are of interest. A geometric coefficient of variation expresses dispersion relative to the geometric mean. It should not be read as a confidence interval, an individual participant range, or a measure of the uncertainty in a comparison.

General explanation: In a crossover study, each participant receives more than one treatment condition in separate periods. A comparison can then use information about both treatment and within-participant variation. A paired analysis may account for the fact that measurements from the same participant can be more alike than measurements from different participants. The registry identifies the design as crossover but does not report the analysis model, treatment sequences, period effects, carryover assessment, or how missing period data were handled. It is therefore not possible to infer which crossover-specific methods were used.

General explanation: A common way to assess pharmacokinetic bioequivalence is to compare exposure measures on a logarithmic scale and express the treatment contrast as a ratio on the original scale. The conclusion is then evaluated against prespecified limits, often using a confidence interval. This describes a general approach, not a claim about the analysis in this trial. The registry does not report a comparative ratio, its confidence interval, the equivalence limits, or a conclusion from a formal bioequivalence analysis.

Randomization is recorded, but the registry does not describe how participants were assigned to treatment sequences or whether sequence allocation was balanced. Masking is recorded as none. An unmasked design does not automatically invalidate a pharmacokinetic measurement, but the absence of masking can matter for procedures or assessments that involve judgment. The endpoint is a measured concentration; the registry does not provide details on laboratory methods, assay performance, sample handling, or quality control. Those details are not reported in the registry record.

The endpoint schedule contains a predose measurement and multiple postdose time points through 168 hours. Cmax is based on the highest observed concentration, so the timing and density of collection can affect whether the observed maximum captures the underlying concentration peak. The record lists measurement times but does not explain how Cmax was derived, including whether it was taken directly from observed samples or estimated by another method. No additional analytical details should be assumed.

The stated analysis population consists of participants who received at least one dose and had evaluable pharmacokinetic data. This definition identifies who could contribute to the primary endpoint, but does not provide the number screened, randomized, treated in each period, or excluded from each analysis beyond the treatment-specific counts. Reasons for nonevaluable data and methods for addressing missing measurements are not reported. The registry also does not report an inferential analysis for the primary endpoint; the posted results are descriptive summaries.

The record lists no posted secondary outcomes and no analyses. The statistical analysis plan, including any prespecified hypotheses, model terms, multiplicity approach, or interim analyses, is not reported in the registry record. General statistical principles cannot fill those gaps. In particular, the descriptive summaries cannot be converted into a formal significance or equivalence conclusion without comparative estimates, uncertainty measures, and the planned decision criteria.

10. Multiplicity, Missing Data and Analysis Populations

The registry records two outcome measures, but no secondary outcomes are posted. It reports the Cmax endpoint as primary and provides descriptive summaries for the reference tablet and both test tablets. No formal analyses are reported. The statistical plan for selecting endpoints, testing contrasts, or controlling multiplicity is not reported in the registry record. It is therefore not possible to determine whether multiple comparisons were planned or how they would have been addressed.

The primary endpoint population is defined as participants who received at least one dose and had evaluable pharmacokinetic data. Treatment-specific counts are 84 for the reference, 81 for Test 1, and 85 for Test 2. Reasons for the different counts, missing concentrations, or nonevaluable pharmacokinetic data are not reported. The record does not state whether any missing measurements were imputed, whether participants were excluded by period, or what rules determined evaluability.

In general, missing data can affect a treatment comparison when the chance of missingness is related to treatment, participant characteristics, or the outcome. For a crossover study, incomplete data in one period can also affect whether a participant contributes to a within-participant contrast. These are general considerations, not reported findings about this study. The posted information does not allow the pattern or potential impact of missing data to be assessed.

The record does not report an interim analysis, a prespecified sample-size justification, or the statistical analysis plan. No formal comparative estimates or confidence intervals are posted. Consequently, neither multiplicity adjustment nor the treatment of missing observations can be evaluated from the registry record.

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 reports zero participants with a serious adverse event in each treatment group: 0 of 84 for the reference tablet, 0 of 81 for Test 1, and 0 of 85 for Test 2. These are counts within the recorded group populations. They describe the serious adverse event results posted for the study and do not establish that serious events are impossible or that risks are identical across formulations.

The registry also lists other adverse events for 33 participants in the reference group, 22 in Test 1, and 23 in Test 2. Those are not serious-adverse-event counts. This safety summary does not identify the events, their severity, timing, duration, or relationship to study treatment. The record describes collection of side-effect information, but the details needed to interpret individual event types are not reported in the registry record.

Death counts are not reported in the registry record. The group counts should be interpreted in light of the study’s healthy-participant population and the exposure described for the trial, without extrapolating beyond these posted observations. Descriptive safety counts alone do not establish comparative safety or causation.

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

The posted results establish that Cmax was summarized for each of the three evacetrapib tablet formulations in a randomized, unmasked crossover study of healthy participants. The geometric mean concentrations were 983 ng/mL for the reference, 1170 ng/mL for Test 1, and 1120 ng/mL for Test 2. The associated geometric coefficients of variation were 78.0, 56.0, and 66.0. These values describe the reported summaries; they are not formal estimates of treatment differences.

The results do not establish that the formulations are bioequivalent or not bioequivalent. A formal conclusion requires a comparative analysis and a prespecified criterion, and those are not reported in the registry record. No confidence intervals or statistical tests are posted for the primary endpoint. The descriptive summaries do not indicate how uncertain a comparison is, nor whether a difference would meet a regulatory or protocol-defined standard.

The study’s design and population also define the reach of the findings. The participants were healthy, and the record describes three single-dose study periods. The results therefore characterize the reported pharmacokinetic measurements in this study setting. They do not, on their own, establish what would occur in other populations, under other dosing conditions, or with repeated use.

The safety data are similarly limited to posted counts. Zero serious adverse events were recorded in each treatment group, while other adverse events were reported for participants in all three groups. The registry does not provide event-level details or a comparative safety analysis. These counts are not a basis for concluding that a formulation is safer or that adverse events were caused by a formulation.

Overall, the record provides descriptive pharmacokinetic and safety information, but leaves important inferential questions unanswered. Absence of a reported comparative result is not evidence that the formulations are equivalent, and the descriptive values alone should not be treated as proof of a treatment difference.

13. Why This Trial Matters Statistically

This study illustrates why the design and the analysis need to be read together. A crossover trial can be useful for comparing formulations because participants receive each condition across separate periods, allowing a comparison that can account for participant-level variation. But the design label alone does not reveal how that comparison was estimated. Here, the registry reports treatment-specific geometric means and variability, but not a paired contrast, model, or confidence interval.

The distinction between descriptive and inferential results is especially important in bioequivalence questions. Three treatment-specific means can describe the observed concentrations, but they do not show whether a formal criterion was met. The registry does not report the equivalence limits or the comparative uncertainty needed to interpret the results against such a criterion. Statistical interpretation should therefore remain limited to the summaries actually posted.

The record also shows why endpoint definitions and analysis populations matter. Cmax is a maximum selected from a concentration profile, and its value depends in part on the measurement schedule and the method used to derive it. The registry lists the sampling times and defines the eligible pharmacokinetic population, but does not give the derivation method or the reasons for treatment-specific differences in participant counts. Those details can affect how a reader interprets a result.

Finally, a completed trial may still have incomplete public reporting of analyses. In this record, the absence of formal analyses, secondary results, and uncertainty estimates limits what can be concluded from the posted outcomes. Recognizing that boundary is part of sound statistical interpretation: report what the summaries show, while distinguishing it from conclusions that require unreported comparisons.

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.

Several trial-specific limitations affect interpretation. The registry reports the primary endpoint summaries but no formal comparison among the reference tablet and the two test tablets. It does not provide treatment-effect estimates, confidence intervals, statistical tests, or a bioequivalence decision. The equivalence margins and the analysis model are not reported in the registry record, so the central formulation-comparison question cannot be resolved from these results alone.

The trial is identified as crossover, but the treatment sequences, allocation procedure, washout details, and handling of period or carryover effects are not reported. The record also does not explain why the numbers contributing to the Cmax summaries differ across formulations. Without those details, it is difficult to assess the extent to which the reported summaries reflect complete paired data.

The endpoint schedule is listed, but the method used to derive maximum observed concentration is not described. Laboratory assay methods and quality-control information are also not reported. These omissions limit assessment of how the measurement was generated and how precisely the reported summaries characterize underlying concentrations.

The primary analysis population is defined, but missing-data reasons, exclusions, and any imputation or sensitivity analyses are not reported. The statistical analysis plan, sample-size justification, and interim analyses are also not reported in the registry record. The safety summary gives counts but not event-level descriptions, timing, severity, or attribution. Finally, the study enrolled healthy participants and describes single doses across three periods; its findings should be understood within that study context.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Different Particle Sizes of Evacetrapib in Healthy Participants — NCT02497391.
• Registry record last updated 2018-12-03; status last verified 2018-11.
• Results first posted 2018-12-03.
• 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

NCT02497391 is a completed, randomized, unmasked Phase 1 crossover study of three 130 mg evacetrapib tablet formulations with different particle sizes in healthy participants. It enrolled 95 participants. The study began in 2015-07 and reached primary completion in 2015-11.

The primary endpoint was maximum observed concentration of evacetrapib, summarized as a geometric mean and geometric coefficient of variation. The reported geometric means were 983 ng/mL for the reference, 1170 ng/mL for Test 1, and 1120 ng/mL for Test 2. The registry does not report formal comparative estimates, confidence intervals, or a bioequivalence conclusion. Serious adverse events were recorded for 0 participants in each group; other adverse events were reported for 33, 22, and 23 participants, respectively.