A Study of Evacetrapib (LY2484595) in Combination With Atorvastatin in Japanese Participants With Primary Hypercholesterolemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Evacetrapib (LY2484595) in Combination With Atorvastatin in Japanese Participants With Primary Hypercholesterolemia (NCT02260648), a randomized phase 3 study. The primary outcome is Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) Measured by Beta Quantification.

2. Clinical Question

The study record describes a phase 3, randomized, double-blind, parallel-group trial. Its stated purpose was to evaluate the efficacy and safety of evacetrapib when given with atorvastatin in Japanese participants with primary hypercholesterolemia. The treatment period was 12 weeks.

The primary endpoint is a laboratory measure of change in LDL-C from baseline. The posted arm estimates describe average percentage change, while the comparison estimates describe the difference between the evacetrapib and placebo arm estimates. The record also includes an ezetimibe reference arm, allowing its posted results to be read alongside those for evacetrapib and placebo. The study record does not report a separate primary question about comparing evacetrapib directly with ezetimibe.

The question is about the results recorded for this trial and their statistical precision. It is not, on its own, a conclusion about clinical benefit, longer-term outcomes, or effects in populations beyond the one described in the registry record.

3. Trial Design

This was a randomized, double-blind, parallel-group phase 3 study. Participants were assigned to evacetrapib, placebo, or ezetimibe, with atorvastatin included in each described regimen. The evacetrapib and placebo groups each received atorvastatin 10 mg once a day for 12 weeks; the evacetrapib group also received evacetrapib 130 mg. The reference group received ezetimibe 10 mg with atorvastatin 10 mg once a day for 12 weeks.

The registry record reports enrollment of 149 participants. It lists the study status as terminated, with a start date of 2015-01 and primary completion in 2015-11. The reason for termination is not reported in the registry record. The original target enrollment, the rationale for that target, and the original design assumptions are not reported in the registry record.

The primary outcome was percent change from baseline to Week 12 in LDL-C measured by beta quantification. The stated analysis used a mixed-effects model for repeated measures, with least-squares mean estimates at Week 12. The record specifies adjustment for baseline measurement and fixed effects for treatment, visit, and the treatment-by-visit interaction, with participant as a random effect. The visit values listed in the model description were 4, 5, 6, or 7.

The analysis population was all participants who received at least one dose of study drug. The arm-level result counts are 53 for evacetrapib, 46 for placebo, and 50 for ezetimibe. The method of sequence generation, allocation concealment, and details of how masking was maintained are not reported in the registry record. The record identifies double masking but does not specify which roles were masked.

There are no reported analysis entries in the registry record. This means that the registry record does not provide a separate entry for the analysis details behind each reported outcome beyond the primary endpoint model description. It does not establish why the trial was terminated or whether other analyses were conducted outside 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

Reasons for not completing this period:

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.

Population: All participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) Measured by Beta Quantification, measured over Baseline, Week 12.

The primary endpoint is percent change from baseline to Week 12 in low-density lipoprotein cholesterol (LDL-C), measured by beta quantification. It captures change in a continuous laboratory measure over the treatment period. A negative percentage change indicates a lower Week 12 value relative to baseline; the endpoint is not itself a count of clinical events.

The reported arm values are least-squares means from the stated mixed-effects model for repeated measures. In general, least-squares means are model-based estimates that account for the variables included in the model, rather than simple unadjusted averages. The registry record says the model adjusted for baseline measurement and included treatment, visit, and treatment-by-visit effects, with participant as a random effect. The posted estimates are for Week 12.

LDL-C is used as the primary measure because the trial was designed to evaluate lipid changes during treatment. The registry record does not state a threshold for what would constitute a clinically important change, nor does it connect the endpoint to longer-term clinical outcomes. Therefore, the percentage change describes the measured lipid response during the trial period; it cannot by itself establish the broader clinical meaning of that response.

The record reports standard errors alongside the arm estimates. A standard error describes the estimated precision of an average, not the spread of individual participants' values. No arm-level confidence intervals are reported for the primary least-squares means.

7. Results Posted in the Registry

• Evacetrapib: mean -26.37 versus -3.75 on control; difference -22.62 (95% CI -31.45 to -13.79), standardized effect d = -1.01; z-test p = <0.001.
• Ezetimibe: mean -27.31 versus -3.75 on control; difference -23.56 (95% CI -32.42 to -14.70), standardized effect d = -1.06; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percent Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol (HDL-C)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Evacetrapib: mean 108.96 versus -0.90 on control; difference 109.86 (95% CI 95.29 to 124.43), standardized effect d = 2.97; z-test p = <0.001.
  • Ezetimibe: mean -3.12 versus -0.90 on control; difference -2.22 (95% CI -16.81 to 12.37), standardized effect d = -0.06; z-test p = 0.766.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Evacetrapib than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ezetimibe and the control. The interval gives the range of effects that remain compatible with the data.

Percent Change From Baseline to Week 12 in LDL-C (Direct)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Evacetrapib: mean -27.17 versus -3.40 on control; difference -23.77 (95% CI -31.47 to -16.07), standardized effect d = -1.22; z-test p = <0.001.
  • Ezetimibe: mean -28.96 versus -3.40 on control; difference -25.56 (95% CI -33.28 to -17.84), standardized effect d = -1.33; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Evacetrapib than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Ezetimibe than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percent Change From Baseline to Week 12 in Non HDL-C

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Evacetrapib: mean -22.01 versus -6.42 on control; difference -15.59 (95% CI -22.57 to -8.61), standardized effect d = -0.88; z-test p = <0.001.
  • Ezetimibe: mean -27.35 versus -6.42 on control; difference -20.93 (95% CI -27.92 to -13.94), standardized effect d = -1.20; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Evacetrapib than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Ezetimibe than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry record lists six secondary outcome measures. Numeric results are available for three of them: HDL-C, direct LDL-C, and non-HDL-C. Results for lipoprotein-a, apolipoprotein A-I, and apolipoprotein B are not reported in the registry record.

Across the available measures, the posted evacetrapib and ezetimibe estimates are more negative than placebo for direct LDL-C and non-HDL-C, while HDL-C shows a strongly positive estimate for evacetrapib relative to placebo. These directions are broadly consistent with the primary finding that the evacetrapib estimate for LDL-C measured by beta quantification was more negative than placebo. The measures are related lipid outcomes, however, and should not be treated as independent confirmations of a single clinical outcome.

The HDL-C comparison between ezetimibe and placebo differs from the pattern of the evacetrapib comparison: its recalculated estimate is -2.22, with a 95% confidence interval from -16.81 to 12.37 and an unadjusted p-value of 0.766. The interval includes zero. This is a result for that secondary contrast, not evidence that the treatments are equivalent.

All posted secondary comparisons are unadjusted recalculations. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for these outcomes. In general, testing several outcomes creates more opportunities for apparently notable results to arise by chance. Without a reported adjustment strategy, secondary p-values carry less confirmatory weight than a prespecified primary analysis, and individual findings should be treated as exploratory. The record does not report whether multiplicity procedures were used outside the registry entry.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percent Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol (HDL-C)
• Percent Change From Baseline to Week 12 in LDL-C (Direct)
• Percent Change From Baseline to Week 12 in Non HDL-C
• Percent Change From Baseline to Week 12 in Lipoprotein-a
• Percent Change From Baseline to Week 12 in Apolipoprotein A-I
• Percent Change From Baseline to Week 12 in Apolipoprotein B

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant has a measured LDL-C value, and the endpoint expresses percentage change from baseline to Week 12. The registry record reports least-squares means and standard errors. The results are therefore model-based summaries of the average change, not counts of participants who crossed a threshold.

What does the repeated-measures model do?

A mixed-effects model for repeated measures uses observations over time while accounting for the fact that measurements from the same participant are related. In general, measurements from one person should not be treated as independent observations. The mixed model represents this within-participant structure through a participant-level random effect. The registry record specifies fixed effects for treatment, visit, and the treatment-by-visit interaction, and adjustment for baseline measurement.

In general, the treatment-by-visit term allows estimated treatment patterns to differ across visits, rather than forcing a single treatment contrast to apply identically at every visit. The model description lists visits 4, 5, 6, or 7, and the reported endpoint estimate is for Week 12. The record does not provide further details about the visit schedule or the model's covariance structure.

How should least-squares means be read?

In general, a least-squares mean is an estimate from a statistical model, conditional on the variables included in that model. Here, the registry record states that the primary model adjusted for baseline and included the specified treatment and visit terms. The arm-level least-squares means should not be assumed to be raw arithmetic averages. A standard error quantifies uncertainty in an estimated mean. It is not the standard deviation of individual participant measurements, and it does not describe the full range of participant responses.

The primary results list an estimate for each arm but do not include confidence limits for those arm-level estimates. The contrast intervals discussed in the interpretation are recalculated, unadjusted comparisons using posted summary statistics. These contrast calculations are not the same as the stated repeated-measures model and do not incorporate its full structure.

What is an unadjusted recalculation?

The registry record gives arm estimates and standard errors, but no reported analysis entries for the posted treatment comparisons. The recalculated contrasts compare the posted estimate in an active arm with the posted placebo estimate. The calculation uses an approximate standard deviation derived from the posted standard errors. As a result, the reported recalculated p-values and confidence intervals are useful for a simple, transparent comparison, but they should not be presented as the trial's reported adjusted analysis.

In general, an unadjusted comparison does not account for additional covariates or design features beyond those represented in the calculation. Here, it does not reproduce the repeated-measures model specified for the primary outcome. The registry record does not provide a separate sponsor-reported treatment contrast against which to compare the recalculation.

What do the p-value and confidence interval convey?

In general, a p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The reported p-values for the recalculated primary contrasts are unadjusted. A confidence interval gives a range of estimates compatible with the data and calculation method at its stated confidence level. It conveys both the direction and the precision of the estimated contrast, but it does not resolve uncertainty about bias, model assumptions, or clinical relevance.

For the primary recalculated contrasts, the intervals lie on the negative side of zero. This corresponds to the direction of the arm estimates: the estimated percentage change was more negative in the active arm than in the placebo arm. The width of an interval indicates statistical precision; a wider interval allows a broader range of plausible contrast values. Neither an interval nor a p-value determines whether a difference matters to patients.

What remains unclear about the analysis?

The registry record identifies the primary analysis population as all participants who received at least one dose of study drug. It does not report details on participant exclusions after treatment, missing outcome values, imputation, or sensitivity analyses. In general, repeated-measures models can use available observations, but conclusions depend on assumptions about why observations are missing and how the model is specified. Those assumptions and supporting checks are not reported in the registry record.

The record also does not report the original sample-size calculation, planned effect size, analysis timing, interim analyses, or multiplicity procedure. These omissions prevent a full assessment of whether the posted analyses follow a prespecified statistical plan. They do not change the numerical results, but they limit how confidently those results can be placed in the intended confirmatory framework.

11. Confidence Intervals and Precision

The primary arm estimates have standard errors of 3.108 for evacetrapib and 3.264 for placebo. These values describe the precision of the estimated arm means. They are not measures of the variability among individual participants. The registry record does not provide confidence intervals for these arm means.

For the recalculated evacetrapib-versus-placebo contrast, the estimate is -22.62 and the 95% confidence interval runs from -31.45 to -13.79. The entire interval is negative, so the calculated range is consistent with a more negative mean percentage change in the evacetrapib arm than in the placebo arm. The interval also shows that the data do not pin down one exact contrast value. Its endpoints represent the range of values compatible with the calculation and its assumptions.

The interval is based on an unadjusted recalculation from the posted summary statistics, using an approximate standard deviation. It is not the confidence interval from the stated mixed-effects model. The registry record does not report a sponsor-derived contrast interval for comparison. Thus, the recalculated interval should be understood as an aid to interpreting the posted arm estimates, not as a fully reported model-based treatment effect.

Confidence intervals address sampling uncertainty under an analysis; they do not account for every source of uncertainty. They cannot establish whether a measured difference is clinically important, whether the analysis was prespecified, whether missing data could bias the result, or whether findings generalize beyond the study population and 12-week period. The registry record does not report a clinical-importance threshold or longer-term follow-up results.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total event counts. The calculation uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original trial's own sample-size assumptions are not reported in the registry record.

In general, power is the probability that a study would detect an effect of a specified size under the assumptions used for planning, if that effect were present. The 80% column gives the per-arm planning count for an 80% chance of detection under those assumptions; the 90% column gives the count for a 90% chance. These are design illustrations based on the observed effects in this trial, not observed power.

The rows represent planning for 100%, 75%, or 50% of the observed effect. A smaller effect is harder to distinguish from random variation, so the corresponding planning figures require more participants per arm. This relationship is general and does not mean that a smaller effect was actually present or that the trial was designed around those smaller effects.

These calculations are illustrative rather than a reconstruction of the trial's original design. They do not account for unreported choices such as anticipated dropout, planned covariate adjustment, multiplicity, or the original target effect. The registry record does not report the original sample-size justification, so the planning figures should not be used to infer the adequacy of the trial's original enrollment.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -22.620; pooled standard deviation σ = 22.401.
2. n = 2 × (1.96 + 0.842)² × 22.401² / -22.620² = 15.4, rounded up to 16 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -22.62                      # observed difference in means
sigma <- 22.4010273843922                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2260648)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 16 (80% power), 21 (90% power)
 75% of observed effect: n per arm = 28 (80% power), 37 (90% power)
 50% of observed effect: n per arm = 62 (80% power), 83 (90% power)
power.t.test: 16.4 
Simulated power at n = 16 per arm: 0.792 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and six secondary outcome measures, but it does not report a procedure for controlling multiplicity across outcomes or comparisons. The posted p-values for the recalculated comparisons are unadjusted. When multiple hypotheses are examined, the chance of at least one apparently unusual result can increase. In general, a prespecified testing hierarchy or adjustment method can help address that issue. No such method is reported in the registry record, so the secondary findings should not be read as a set of confirmatory tests.

The primary endpoint description provides the model structure and analysis population, but the registry record does not report the original statistical analysis plan, whether the plan changed, or whether there were interim analyses. The reason the trial was terminated is also not reported in the registry record. These details matter when assessing how the posted findings relate to the planned analyses, but their absence does not establish that any particular analysis was or was not conducted.

The stated primary population includes participants who received at least one dose of study drug. The record does not report how many participants had a Week 12 measurement, how missing measurements were handled, or whether participants were excluded from the analysis after receiving treatment. It does not describe imputation, sensitivity analyses, or assumptions about missing outcomes. In general, missing-data assumptions can affect estimates when the likelihood of an outcome being unavailable is related to the outcome itself or to treatment.

The registry record reports zero serious adverse events in each listed at-risk group, but it does not provide death counts. The reason for the trial's terminated status and any consequences for data collection are not reported in the registry record. These gaps limit assessment of completeness and analysis choices. They should be distinguished from the reported outcome estimates, which describe the results entered in the record.

15. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures list zero affected participants in the evacetrapib group, zero in the placebo group, and zero in the ezetimibe group. The corresponding at-risk counts are 53, 46, and 50. These are registry-reported counts; they do not establish that the treatments have no serious risks or that no events occurred outside the recorded period or definitions.

The record lists other adverse events affecting 18 participants in the evacetrapib group, 13 in the placebo group, and 12 in the ezetimibe group. These are counts of affected participants, not event rates, and the record does not provide comparative statistical analyses for them. No serious adverse event terms are listed. Death counts are not reported in the registry record.

The registry record does not provide event-level descriptions or enough information to assess timing, severity categories beyond serious versus other adverse events, or causal attribution. The counts should therefore be read as a limited summary of the safety information entered in the record, not as a complete comparison of safety profiles.

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

The posted primary results show a more negative Week 12 least-squares mean percent change in LDL-C measured by beta quantification for evacetrapib than for placebo, with atorvastatin included in both regimens. The recalculated unadjusted contrast is -22.62, and its 95% confidence interval is from -31.45 to -13.79. The same general direction appears in the available posted results for direct LDL-C and non-HDL-C. These observations describe changes in lipid measures during the 12-week trial.

They do not, by themselves, establish a clinically important benefit. The registry record does not state a threshold for clinical importance or report longer-term clinical outcomes. A laboratory change is not interchangeable with evidence about events, symptoms, or outcomes outside the measured period. The record also does not provide enough information to assess how missing observations or multiplicity were handled.

The recalculated comparisons are unadjusted and use approximate standard deviations derived from posted standard errors. They are not the same as treatment contrasts estimated by the repeated-measures model. The arm estimates themselves are model-based least-squares means, but no sponsor-reported primary contrast analysis is listed in the registry record. Accordingly, the recalculated results support a limited statistical description of the posted values, not a definitive account of all analyses conducted for the trial.

The inclusion of an ezetimibe reference arm does not establish a formal comparison between ezetimibe and evacetrapib. Similar-looking estimates do not demonstrate equivalence or non-inferiority. Likewise, the study's randomized, double-blind design is relevant to its intended comparison, but the registry record does not report all operational details needed to assess conduct, including the allocation method and how masking was maintained.

The results apply to the Japanese participants with primary hypercholesterolemia included in this 12-week study. The registry record does not support conclusions about other populations, longer treatment periods, or outcomes not reported. Its terminated status is recorded, but the reason is not reported in the registry record, so no explanation for that status can be inferred.

17. Why This Trial Matters Statistically

This trial illustrates why a posted arm estimate and a treatment contrast are not interchangeable. The registry record reports model-based least-squares means for each arm, along with standard errors. A comparison between arms requires an additional contrast estimate and its uncertainty. The contrasts discussed for this trial are recalculated from summary statistics and are not the reported output of the specified repeated-measures model.

It also shows why analysis methods matter for longitudinal outcomes. The stated model accounts for repeated measurements within participants and includes baseline, visit, and treatment-by-visit terms. A simple contrast from arm-level summaries does not reproduce that modeling structure. The recalculation can help readers understand the direction and approximate size of the observed difference, while its assumptions and status should remain clear.

The study provides a useful example of separating statistical evidence from clinical interpretation. The primary contrast has a confidence interval that lies below zero, but the record does not report a clinical-importance threshold or longer-term outcomes. Statistical precision answers how narrowly an estimate is located under a calculation; it does not decide whether the result matters clinically.

Finally, the record highlights the importance of reporting multiplicity, missing-data handling, sample-size rationale, and analysis populations. It gives a primary model description and lists an analysis population, yet several details needed for a full appraisal are not reported. Readers can interpret the posted results while recognizing that incomplete reporting limits what can be concluded about the prespecified analysis strategy and the completeness of the evidence.

18. 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 primary arm estimates are reported with standard errors but without arm-level confidence intervals. The treatment contrasts presented alongside them are recalculated, unadjusted comparisons based on approximate standard deviations rather than reported adjusted contrasts from the stated mixed-effects model. This difference in source and method limits direct interpretation of the recalculated intervals as the trial's definitive model-based results.

The registry record does not report the original sample-size calculation or the assumptions used to set the trial's target enrollment. Its terminated status is recorded, but the reason for termination is not reported in the registry record. The record also does not describe interim analyses or provide the original statistical analysis plan.

Missing-data details are not reported: the number of participants with Week 12 outcomes, the handling of unavailable measurements, and any sensitivity analyses are not specified. The record identifies the analysis population as participants who received at least one dose, but does not give further detail about analysis exclusions or adherence to assigned regimens.

Only three of the six listed secondary outcomes have numeric results in the registry record. No multiplicity procedure is reported, and the available secondary comparisons are unadjusted recalculations. Safety reporting is limited to group counts for serious and other adverse events; death counts are not reported in the registry record, and no serious event terms are listed.

The study concerns Japanese participants with primary hypercholesterolemia and a 12-week treatment period. The registry record does not provide longer-term outcomes or support conclusions about other populations. It also does not specify all details of allocation concealment or masking procedures.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study of Evacetrapib (LY2484595) in Combination With Atorvastatin in Japanese Participants With Primary Hypercholesterolemia — NCT02260648.
• 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.

22. Record Summary

The registry record describes a randomized, double-blind, parallel-group phase 3 study of evacetrapib with atorvastatin in Japanese participants with primary hypercholesterolemia. Enrollment was 149, and status is listed as terminated. The start date was 2015-01 and primary completion was 2015-11; the reason for termination is not reported in the registry record.

The primary outcome was percent change from baseline to Week 12 in LDL-C measured by beta quantification. The stated analysis used a mixed-effects model for repeated measures and included participants who received at least one dose of study drug. The posted primary arm estimates were -26.37 for evacetrapib and -3.75 for placebo. The recalculated unadjusted contrast was -22.62, with a 95% confidence interval from -31.45 to -13.79 and p < 0.001.

These recalculated comparisons are not reported adjusted model contrasts. The registry record does not report multiplicity procedures, missing-data details, the original sample-size justification, or the reason for termination. Numeric secondary results and safety counts are available, but the record's reporting gaps limit broader interpretation.