Exploratory Study of the Effects of Omega-3-acid Ethyl Esters on the Lipid and Lipoprotein Profile in the Blood: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Exploratory Study of the Effects of Omega-3-acid Ethyl Esters on the Lipid and Lipoprotein Profile in the Blood (NCT02839902), a randomized phase 4 study. The primary outcome is Percent Changes From Baseline in Concentration of Major 4 Lipid Constituents in Small Dense Low Density Lipoprotein (sdLDL) Fraction.

2. Clinical Question

The study was designed to explore changes in lipid and lipoprotein profiles in blood, using HPLC, among hyperlipidemic participants already receiving a HMG-CoA reductase inhibitor. The primary outcome concerns percent change from baseline in the concentration of four lipid constituents in the small dense low-density lipoprotein fraction. It is therefore a laboratory-measure question about lipid composition over the recorded treatment period, rather than a question about clinical events.

The registry record describes a randomized, parallel-group comparison. The intervention group continued the stable background regimen and received TAK-085; the control group continued the background regimen without omega-3-acid ethyl esters. The record does not report numerical primary-outcome results, so the direction and magnitude of any between-group difference cannot be stated. Nor does the record establish whether a difference was statistically distinguishable from chance or estimated precisely.

3. Trial Design

This was a Phase 4 randomized, parallel-group study with no masking. The registry lists an enrollment of 53 and a completed status. The recorded study dates are 2016-12-27 for the start and 2017-08-30 for primary completion. Takeda is listed as the sponsor.

Participants in the TAK-085 group received omega-3-acid ethyl esters at a total dose of 4 g per day for 8 weeks, in addition to a consistent HMG-CoA reductase inhibitor regimen. That background regimen had been started at least 4 weeks before informed consent and was to remain at a consistent dose. The control group received the stable HMG-CoA reductase inhibitor regimen only. The registry describes the intervention as oral capsules taken immediately after meals twice daily.

Randomization allocates participants to study groups by chance. In general, this can reduce systematic differences between groups at the outset, although it does not guarantee that all participant characteristics will be balanced, particularly in a study of this size. The parallel design means participants were assigned to one group rather than being described as switching between treatments. The study was unmasked, so participants and study personnel were not blinded to group assignment according to the registry’s masking description. The record does not report whether outcome assessment or laboratory analysis was masked separately.

The primary outcome was assessed at baseline, Week 4, and Week 8. The outcome definition describes percent changes from baseline at Week 4 and Week 8 for cholesterol, triglycerides, free cholesterol, and phospholipid in the small dense LDL fraction. The registry also lists secondary outcomes covering lipid constituents in other lipoprotein fractions, fatty acids, and fatty-acid ratios. The record lists 16 outcome measures and 9 analyses, but those counts do not by themselves explain how individual measurements were organized or statistically modeled.

The registry defines the full analysis set as participants who were randomized and received at least one dose of study drug. It does not report additional detail about the number analyzed for each outcome, adherence, withdrawals, or the treatment of missing measurements. These distinctions matter when interpreting estimates: the number enrolled is not necessarily the number contributing data to every time point and outcome.

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 with a historical diagnosis of hyperlipidemia who were inadequately controlled while receiving a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor were enrolled in one of two groups, treatment group with omega-3-acid ethyl esters (TAK-085) 2 grams (g) and treatment group without TAK-085 (Control Group).

Overall Study

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS); FAS was defined as participants who were randomized and received at least one dose of the 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: Full analysis set (FAS); FAS was defined as participants who were randomized and received at least one dose of the study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percent Changes From Baseline in Concentration of Major 4 Lipid Constituents in Small Dense Low Density Lipoprotein (sdLDL) Fraction, measured over Baseline, Week 4 and Week 8.

The primary endpoint is percent change from baseline in the concentration of four major lipid constituents—cholesterol, triglycerides, free cholesterol, and phospholipid—in the small dense low-density lipoprotein fraction. The registry specifies measurements at baseline, Week 4, and Week 8, with the reported changes referring to Week 4 and Week 8. Concentrations were assessed as part of a lipid and lipoprotein profile using HPLC, as described in the study summary.

Percent change expresses a measurement relative to its starting value, allowing the reported outcome to describe change from each participant’s baseline rather than only a follow-up concentration. That can be useful when participants begin with different baseline concentrations. The endpoint remains a laboratory measure: it does not directly quantify symptoms, clinical events, or quality of life.

The registry identifies the outcome as a mean of a continuous measure and names standard deviation as its dispersion statistic. This tells readers the intended summary format, but not the actual group means, variation, or comparison. Those numerical outcome results are not reported in the registry record. Without them, the endpoint definition alone cannot show the size, direction, or precision of a treatment-group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes continuous lipid outcomes summarized as means with standard deviations. It does not report the detailed statistical methods used to compare groups or time points. The explanations below are general statistical context, not a claim about an unreported analysis plan.

What does a mean and standard deviation describe?

For a continuous measure, the mean summarizes the group’s average value. The standard deviation describes how much individual measurements vary around that average. These summaries answer different questions: a mean locates the center of the observed measurements, while a standard deviation describes their spread. A standard deviation is not the uncertainty in the group mean or in a treatment-group contrast. Precision of an estimate is usually conveyed by a standard error or confidence interval, but the primary-outcome confidence intervals and standard errors are not reported in the registry record.

The primary measure is percent change from baseline in concentrations of four lipid constituents in the small dense LDL fraction. In general, a change score uses a participant’s baseline measurement as a reference for interpreting follow-up. Percent change can make relative changes easier to compare when starting levels differ, but its behavior can depend on the baseline values and on how missing or zero values are handled. The registry does not report those implementation details. It also does not report whether the group comparison used change scores, follow-up values adjusted for baseline, or another model.

How should a confidence interval be understood?

General explanation: a confidence interval expresses the statistical uncertainty around an estimate under specified assumptions and a chosen method. A narrow interval indicates greater precision than a broad interval, while an interval that includes values on both sides of no difference may be compatible with more than one interpretation. The interval does not establish that a treatment effect is clinically important, and it does not substitute for examining the estimate itself. The registry record does not give primary-outcome estimates or confidence intervals, so no such precision assessment can be made for these results.

A p-value, if reported, addresses how unusual the observed data would be under a particular null hypothesis and analysis model. It does not measure the probability that the null hypothesis is true, nor does it describe the size or importance of a difference. The registry record does not report primary-outcome p-values. A p-value alone would also be insufficient to understand the pattern across the multiple lipid constituents and time points.

What does randomization contribute?

General explanation: random allocation is intended to make treatment assignment independent of participant characteristics. It can support a causal comparison when the trial is conducted and analyzed appropriately, but chance imbalances can remain. Randomization also does not solve missing-data problems, correct measurement errors, or remove the need to define the analysis population. In this study, the registry lists randomized allocation and defines the full analysis set as participants who were randomized and received at least one dose. The record does not report the randomization procedure or details of any allocation concealment.

The parallel design compares groups followed under their assigned regimens. The no-masking description means the study is not presented as blinded. General statistical considerations include the possibility that awareness of assignment affects treatment behavior, reporting, or study procedures. This concern can differ for laboratory outcomes compared with subjective outcomes, but the record does not state whether laboratory personnel were masked or how specimens were handled.

How should repeated measurements be considered?

Baseline, Week 4, and Week 8 measurements are taken at different times from the same participants. General explanation: repeated measurements from one participant are usually correlated rather than independent. An analysis that uses all time points together generally needs to account for this within-participant relationship. Alternatively, an analysis may focus on a prespecified time point or on change from baseline. Each approach answers a somewhat different question and relies on assumptions. The registry record does not report which approach was used, whether a repeated-measures model was fitted, or how baseline values entered the analysis.

Variation can also differ across measurements or groups. In general, over-dispersion means the data vary more than a chosen model expects; if unaccounted for, uncertainty can be understated. The registry gives standard deviation as the outcome’s dispersion summary, but does not report diagnostics for distributional assumptions, transformations, or adjustments for unequal variability. It is therefore not possible to assess those modeling choices from the record.

What is the role of the planning illustration?

The accompanying sample-size section is a planning illustration based on the observed effect, rather than the trial’s original design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For continuous outcomes, the illustration is described in participants per arm for 80% power or other displayed power levels. These are planning scenarios, not observed power and not evidence that the trial was adequately or inadequately powered. The registry record does not report the original sample-size justification. No specific planning estimate is repeated because numerical rows are not included in this record summary.

10. Multiplicity, Missing Data and Analysis Populations

The outcome set covers multiple lipid constituents, lipoprotein fractions, fatty-acid measures, and ratios. The primary outcome itself includes four constituents measured at Week 4 and Week 8. When many comparisons are examined, the chance of seeing at least one apparently notable result by chance can increase. General approaches to multiplicity include identifying a prespecified primary contrast, adjusting significance thresholds, or interpreting secondary findings as exploratory. The registry record does not report whether any multiplicity adjustment, testing hierarchy, or other strategy was used. The study is described as exploratory, but that description does not specify how its comparisons were analyzed.

The registry defines the full analysis set as randomized participants who received at least one dose of study drug. That definition is available, but the record does not report outcome-specific numbers analyzed, withdrawals, or the handling of participants with incomplete measurements. It also does not report imputation methods, assumptions about missingness, or sensitivity analyses. These details matter because observed measurements may not represent all randomized participants if data are missing, and the validity of an analysis can depend on why measurements are missing.

The registry lists 16 outcome measures and 9 analyses, but those counts do not reveal which measurements were combined into each analysis, which comparisons were primary, or how missing data and repeated measurements were handled. These analysis details are not reported in the registry record. Readers should distinguish the stated analysis population from the number contributing to any particular estimate, which is not available in this summary.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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 lists no serious adverse events among the 24 participants at risk in the TAK-085 group and none among the 29 participants at risk in the control group. It records 2 participants affected by other adverse events among 24 at risk in the TAK-085 group, and 0 among 29 at risk in the control group. Deaths are listed as 0 in both groups. No serious adverse-event terms are listed.

These are descriptive counts in the registry record. They do not identify the nature, timing, severity, or relatedness of the other adverse events, and the record does not explain how events were collected or classified. The counts alone cannot establish whether an event was caused by a study treatment. A zero count in this study also does not show that an event is impossible or exclude uncommon harms. The figures should be read alongside the study’s limited enrollment and 8-week treatment period, and not as a complete characterization of safety.

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

This trial addresses a specific statistical question: whether an 8-week course of TAK-085 added to a stable HMG-CoA reductase inhibitor regimen was associated with different changes in selected lipid measures than the background regimen alone. Its primary endpoint is a set of laboratory measurements in the small dense LDL fraction. That scope is narrower than an assessment of clinical outcomes, and the registry does not report clinical-event endpoints in the registry record.

The registry record gives the design, intervention, comparator, endpoint definitions, and adverse-event counts, but it does not include numerical primary-outcome results in this summary. Consequently, the available information cannot establish the direction or size of a treatment-group difference, how consistent it was across lipid constituents, or how precisely it was estimated. It also cannot support a claim that there was no difference: missing numerical results in this record are not the same as an observed null result.

Even if a laboratory difference is reported elsewhere in the posted results, its interpretation would depend on the estimate, its uncertainty, the specific time point and constituent, and how multiple outcomes were handled. A statistically distinguishable estimate would not by itself show clinical importance. Conversely, an imprecise estimate would not prove that groups were identical. The planning illustration, where displayed, is not observed power and should not be used to make either conclusion.

The trial’s randomized structure supports a comparison between the assigned regimens, while its open-label design, study population, short treatment period, and analysis details frame how broadly findings can be interpreted. The record concerns hyperlipidemic participants on stable background treatment; it does not establish applicability to populations outside that setting. The reported adverse-event counts are limited descriptive information and do not substitute for a comprehensive safety assessment.

13. Why This Trial Matters Statistically

This study is statistically interesting because it evaluates several related but distinct components of a lipid profile rather than relying on a single broad measure. The primary endpoint separates four constituents within the small dense LDL fraction, and the secondary outcomes extend across other lipoprotein fractions and fatty-acid measures. Such breadth can help describe a biochemical profile, but it creates an interpretation challenge: results must be read by outcome and time point, and the record’s statistical approach to multiple comparisons matters.

The design also makes the distinction between an outcome definition and an outcome result especially important. A clearly defined percent-change endpoint tells readers what was intended to be measured, but not what was observed. Without the actual group estimates and their uncertainty, the statistical evidence cannot be judged from the endpoint description alone. This is a useful reminder to separate the study question, the analysis plan, and the numerical results when reading a registry record.

The registry specifies a mean and standard deviation for continuous outcomes and identifies an analysis population, but the additional details needed to evaluate estimation are not reported. In particular, the handling of measurements over time, missing data, and multiplicity is not stated in this summary. Those details affect how estimates should be interpreted, especially when there are several measures and follow-up points.

Finally, the sample-size section is described as a planning illustration based on the observed effect. That distinction is important: a retrospective illustration can show how planning assumptions relate to an effect size, but it does not reveal the original rationale for enrollment and is not observed power. Separating those concepts helps prevent a planning calculation from being mistaken for evidence about the strength of the trial’s results.

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 registry record does not report numerical results for the primary endpoint, including the group means, standard deviations, between-group estimates, confidence intervals, or p-values. This is the central limitation for interpreting the lipid findings on this page: the endpoint is described, but its observed pattern and precision cannot be assessed from the information.

The study enrolled 53 participants and treated participants for 8 weeks. Those features limit the scope of what can be inferred about patterns over longer periods or outcomes that are not measured in the study. The record concerns hyperlipidemic participants receiving a stable HMG-CoA reductase inhibitor regimen, so it does not directly characterize other populations or treatment settings.

The trial was randomized but unmasked. The registry does not report whether laboratory personnel were masked, or provide further details about allocation procedures. The record also does not report outcome-specific analysis counts, withdrawals, missing-data handling, or sensitivity analyses. Those omissions make it difficult to assess how the analysis population differed from the participants contributing measurements at each time point.

The primary outcome comprises several constituents and two follow-up times, while the secondary outcome list spans multiple fractions and measures. The registry record does not report a multiplicity strategy or a detailed statistical model for repeated measurements. In addition, the adverse-event figures are counts without event descriptions or causal assessments. These limitations do not establish that the study’s analyses were inappropriate; they identify information that is not reported in the registry record and that would be needed for a fuller appraisal.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Exploratory Study of the Effects of Omega-3-acid Ethyl Esters on the Lipid and Lipoprotein Profile in the Blood — NCT02839902.
• Registry record last updated 2019-02-11; status last verified 2018-08.
• Results first posted 2019-02-11.
• 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

NCT02839902 is a completed Phase 4, randomized, open-label, parallel-group study sponsored by Takeda. It enrolled 53 participants with hyperlipidemia. The intervention was TAK-085 omega-3-acid ethyl esters at 4 g per day for 8 weeks, added to a stable HMG-CoA reductase inhibitor regimen; the control group continued the stable regimen without omega-3-acid ethyl esters.

The primary endpoint was percent change from baseline in cholesterol, triglycerides, free cholesterol, and phospholipid concentrations in the small dense LDL fraction, assessed at Week 4 and Week 8. The registry record does not report numerical primary-outcome results or detailed methods for handling multiplicity, missing data, or repeated measurements. It lists no serious adverse events and no deaths in either group, and records 2 participants affected by other adverse events in the TAK-085 group and 0 in the control group.