Pharmacodynamic Effects of a Free-Fatty Acid Formulation of Omega-3 Pentaenoic Acid in Adults With Hypertriglyceridemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacodynamic Effects of a Free-Fatty Acid Formulation of Omega-3 Pentaenoic Acid in Adults With Hypertriglyceridemia (NCT04177680), a randomized phase 2 study. The primary outcome is Percent Change in Plasma Triglycerides (Pharmacodynamic Population).

2. Clinical Question

NCT04177680, the ENHANCE-IT trial, addresses a pharmacodynamic comparison between MAT9001 and icosapent ethyl in adults with hypertriglyceridemia. The primary endpoint is a change in a blood lipid measure over treatment, rather than a clinical event or a measure of symptoms. The main posted values describe the median percent change in plasma triglycerides for the pharmacodynamic population.

The registry describes a randomized crossover study with no masking. Its primary population is defined as all patients with measurable results who received both drugs. That framing makes the question a comparison of treatment periods in people exposed to both interventions, rather than a comparison of two wholly separate groups who each received only one study drug. The record does not provide enough detail to describe the treatment sequence or other features of the crossover procedure.

The posted results can therefore describe the triglyceride changes observed during the two treatment conditions. They do not, by themselves, establish the size or uncertainty of a formal within-person treatment contrast. No between-treatment estimate or statistical test is posted in the record.

3. Trial Design

This was a phase 2, randomized, unmasked crossover trial with a planned enrollment of 100. The registry lists the condition as hypertriglyceridemia and identifies Matinas BioPharma Nanotechnologies, Inc. as the sponsor. The study is marked completed. The recorded start date is 2020-06-03 and the primary completion date is 2020-11-27.

The two drug interventions were omega-3 pentaenoic acid, identified as MAT9001, and icosapent ethyl, identified as Vascepa. Each arm description specifies 2g capsules twice daily with meals. Because the design is crossover, the central comparison concerns the two treatment conditions experienced by participants. The primary analysis population is expressly limited to patients with measurable results who received both drugs.

The primary outcome is percent change in plasma triglycerides from baseline to the end of treatment, with the timeframe stated as baseline to 28 days. The registry identifies the reported summary as a median and lists inter-quartile range as the dispersion measure. It records 94 participants for each treatment result. In a crossover design, equal arm counts should not be read as evidence that these are independent groups; the record describes a population that received both drugs.

The registry does not report treatment order, duration of any interval between treatment periods, washout procedures, masking details beyond none, or the method used to handle possible period or sequence effects. It also does not report a sample-size justification or a detailed protocol for the statistical comparison. Those omissions limit how fully the design can be reconstructed from the registry record alone.

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: Crossover study - each patient received both treatments

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients with measurable results who received both drugs

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 Percent Change in Plasma Triglycerides (Pharmacodynamic Population), measured over baseline to 28 days.

The primary endpoint measures the percent change in plasma triglycerides from baseline to the end of a treatment period, with the timeframe recorded as baseline to 28 days. Triglycerides are a component of plasma lipids, so a change in this measure provides a pharmacodynamic description of how the measured lipid concentration differs after treatment relative to its baseline value. The endpoint is not a clinical outcome such as a cardiovascular event, and a change in this laboratory measure does not itself establish a change in health outcomes.

The registry specifies the median percent change as the summary statistic and identifies the inter-quartile range as the dispersion measure. A median describes the middle of the observed distribution and is less affected by unusually high or low values than the arithmetic mean. An inter-quartile range describes the spread of the central portion of the observations. These summaries can be useful when participant-level changes are skewed or contain influential extremes, although the registry does not explain why these particular summaries were selected.

For MAT9001, the posted median is -20.9, with reported bounds of -24.6 and -17.1. For icosapent ethyl, the posted median is -18.3, with reported bounds of -22.1 and -14.3. These are arm-level summaries. The record does not post a direct estimate of the paired treatment contrast, its uncertainty, or a test of the difference between treatment conditions. The endpoint therefore conveys the observed change within each treatment condition, but does not alone quantify the precision of the comparison between drugs.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a median summarize?

The median is the middle value when observations are ordered. It gives a measure of the center of a distribution without relying on the arithmetic average. This can be informative when changes vary substantially between participants or when a small number of unusually large observations could pull an average away from the typical observation. The registry identifies the median as the primary outcome summary, but does not state the rationale for choosing it or describe the distribution of individual changes.

The inter-quartile range describes the middle portion of the observed values, from the lower quartile to the upper quartile. It is a measure of variability, not an estimate of the uncertainty in the median treatment effect or in the contrast between treatments. The registry lists inter-quartile range as the dispersion measure, while the primary arm results report lower and upper bounds. The record does not explain how those bounds relate to the stated dispersion measure, so they cannot be assigned a more specific statistical interpretation from the available information.

Why does the crossover design matter?

In a crossover trial, participants receive more than one treatment condition. Measurements from the same person are related, because each person brings their own underlying characteristics and baseline levels to both periods. A direct treatment comparison can use this paired structure, often by analyzing each participant’s change under one treatment relative to that same participant’s change under the other. That is different from treating the treatment groups as independent samples.

The registry identifies this study as crossover and defines the primary population as people with measurable results who received both drugs. It does not report the treatment sequence, period-specific procedures, washout details, or a statistical model for paired outcomes. Without those details, readers cannot assess how the analysis addressed potential period or sequence effects. The separate arm medians do not contain enough information to reconstruct the distribution of within-person contrasts.

What does a confidence interval generally convey?

In general, a confidence interval is an interval estimate intended to communicate the uncertainty around an estimated quantity under a specified statistical procedure. An interval for an individual treatment summary and an interval for a between-treatment contrast answer different questions. For a comparative claim, the interval for the contrast is especially relevant because it directly describes the range of values compatible with the estimated difference under the analysis assumptions. The registry does not post such an interval for the treatment contrast in this primary outcome.

The reported lower and upper bounds for each treatment result should therefore be read cautiously. They are not identified as a confidence interval for the comparison, and the record does not spell out their exact statistical meaning. Separate bounds around two treatment summaries cannot by themselves establish the precision or statistical significance of a paired effect.

What is the role of a statistical test?

In general, a statistical test evaluates how compatible observed data are with a specified null hypothesis, given the assumptions of the test. A p-value is not the probability that a treatment is effective, nor does it describe the size or practical importance of an effect. For a crossover comparison, the test would need to reflect the paired data structure and the analysis plan. No p-value or formal treatment-comparison test is reported for the primary endpoint in the registry record.

A statistically significant result, if one were reported, would not by itself establish clinical importance. Conversely, the absence of a posted test does not establish that the treatments are the same. The primary outcome summaries describe changes within the treatment conditions, but the registry record does not provide the inferential results needed to assess a formal comparison.

How should sample-size planning be distinguished from trial results?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, allocation, and chosen error rates. A planning illustration is not an observed result and does not describe the precision achieved in the completed trial. The registry record does not report the trial’s own sample-size justification, target effect, or the assumptions used for its original design. It would therefore be inappropriate to infer the design’s intended power or adequacy from the planned enrollment alone.

The record gives planned enrollment as 100 and reports 94 participants in each primary treatment result. Those counts describe enrollment and the posted outcome population; they do not replace a direct estimate of uncertainty for the paired treatment contrast. No observed-power conclusion can be drawn from these values.

More broadly, the posted primary endpoint is an outcome-level summary, not a complete statistical analysis. The registry does not report a detailed model, adjustment variables, handling of repeated periods, sensitivity analyses, or a treatment-contrast estimate. Readers can interpret the medians as descriptive pharmacodynamic findings, while recognizing that the information required to independently evaluate the comparative inferential analysis is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four secondary outcomes: percent change in other plasma lipoprotein lipids in the pharmacodynamic population; percent change in lipoprotein lipids in the per protocol population; percent changes in apolipoproteins, PCSK9 and hs-CRP in the pharmacodynamic population; and percent change from baseline in omega-3 fatty acid concentrations in the pharmacodynamic population. These outcomes address several laboratory measures and analysis populations in addition to the primary triglyceride endpoint.

When a study examines multiple outcomes, the chance of obtaining at least one apparently notable result can increase if each is tested without accounting for multiplicity. In general, a prespecified testing hierarchy or multiplicity adjustment can help control that issue. The registry record does not report whether a multiplicity strategy was planned or used, how secondary outcomes were prioritized, or whether any outcome testing was confirmatory or exploratory. It also does not post analyses for the secondary outcomes in the information summarized by this record.

The primary population is defined as all patients with measurable results who received both drugs, and the primary result lists 94 participants for each treatment. The registry does not explain how missing or unmeasurable values were handled, whether all participants completed both treatment periods, or whether imputation or other missing-data methods were used. It does not report reasons for missing observations or a comparison of participants included and excluded from the pharmacodynamic population.

The record names both pharmacodynamic and per protocol populations among the secondary outcomes, but does not provide detailed definitions of these populations. It also does not report interim analyses or stopping rules. These omissions make it difficult to assess the potential influence of missing measurements, population selection, or multiple testing on the interpretation of the primary and secondary findings.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety record reports zero serious adverse events among 97 participants in the MAT9001 group and zero among 100 participants in the icosapent ethyl group. It also reports zero deaths in each group. No serious adverse-event terms are listed. These are counts of events or affected participants as represented in the registry record; they do not show that the risk of serious events is absent.

The registry also records other, non-serious adverse events affecting 43 participants in the MAT9001 group and 28 in the icosapent ethyl group. The serious-event and other-event entries should be kept distinct: the latter do not indicate serious events. The record does not give event-level details, severity categories beyond the serious-versus-other distinction, timing, duration, or an assessment of whether events were judged related to treatment.

In general, observing no serious events in a study does not rule out uncommon harms. Safety interpretation depends on the number of people observed, the period of observation, the event definitions, and completeness of reporting. This trial’s crossover design and the different at-risk counts listed for the treatment groups also mean that the entries should not automatically be treated as independent parallel-group risk estimates. The registry record does not provide a comparative safety analysis or enough detail to quantify a treatment-related difference.

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

The primary results describe the median percent change in plasma triglycerides during two treatment conditions in a randomized, unmasked crossover trial. The median was -20.9 for MAT9001 and -18.3 for icosapent ethyl, with 94 participants recorded for each result. These are descriptive summaries of a laboratory endpoint among participants with measurable results who received both drugs.

The results do not establish that one treatment is superior, equivalent, or non-inferior to the other. Such conclusions require a direct comparison that reflects the crossover design, along with an estimate of the treatment contrast and its uncertainty. The registry does not report those inferential results. Different arm-level medians alone do not show whether the observed contrast is precise, whether it is consistent across participants, or whether it is larger than could plausibly arise from sampling variation.

The endpoint is pharmacodynamic: it measures a change in a plasma lipid value over the stated treatment timeframe. It is not a measure of symptoms, cardiovascular events, or long-term outcomes. A change in this laboratory measure should not be equated with a change in those outcomes, and the registry record does not report evidence connecting the primary result to them.

The findings also apply to the stated analysis population, not necessarily to every person with hypertriglyceridemia. The primary population required measurable results and receipt of both drugs. The record does not give enough information to assess how missing results or exclusions might affect representativeness. The unmasked design and unavailable details about treatment periods and analysis methods are additional considerations when interpreting a comparative result.

Accordingly, the posted data describe negative median triglyceride percent changes during both treatment conditions, but leave the comparative uncertainty and clinical implications unresolved. The findings should be read as a limited pharmacodynamic account rather than a complete assessment of comparative benefit or harm.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its crossover design changes the structure of the comparison. The same participants received both drugs, and the primary population requires measurable results after receiving both. In such a design, within-person comparisons can account for stable differences between participants, but the analysis must also respect the repeated treatment periods. The registry’s separate medians do not show the paired differences that would be central to a direct comparative estimate.

The trial also illustrates the distinction between an outcome summary and an inferential comparison. A median for each treatment condition describes the center of each set of observed changes. It does not directly report the treatment contrast, its uncertainty, or a test of whether the contrast is distinguishable from no difference. Readers need that comparative information to evaluate precision, rather than relying on separate summaries alone.

Another important statistical issue is that the primary endpoint is a surrogate laboratory measure, while the record also lists several secondary lipid and biomarker outcomes. Multiple measures can broaden the pharmacodynamic picture, but they also raise questions about endpoint prioritization and multiplicity. The registry does not report how those issues were handled or provide the secondary analyses in the record.

Finally, the safety entries show why event counts need context. No serious adverse events and no deaths are reported, but the record does not provide a comparative safety model or detailed event timing. In a completed trial with a defined analysis population, the distinction between observed counts and precise estimates is essential. These features make the record useful for understanding the trial’s endpoint and design while also showing why registry summaries cannot replace a fully reported analysis.

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 provides arm-level medians and bounds for the primary endpoint but does not report a direct treatment contrast, confidence interval for that contrast, or p-value. This is a central limitation for interpreting a comparative crossover trial. The bounds accompanying each arm’s result are not fully characterized in the record, despite the stated dispersion measure of inter-quartile range.

Important crossover details are not reported in the registry record, including treatment order, period structure, washout procedures, and the method used to account for period or sequence effects. Without these details, readers cannot assess whether the analysis appropriately addressed factors that can influence repeated measurements. The record also does not provide a participant-level account of paired responses.

Missing-data methods and the reasons for missing or unmeasurable results are not reported. The primary population is restricted to participants with measurable results who received both drugs, but the record does not clarify how many participants were excluded from this population, whether all completed both treatment conditions, or how exclusions may have affected the findings. Definitions of the pharmacodynamic and per protocol populations are also not given in detail.

The statistical analysis plan, sample-size justification, adjustment strategy, and multiplicity approach are not reported in the registry record. Nor are secondary outcome analyses included in the posted results. The study was unmasked, which may be relevant to conduct and assessment of some outcomes, although the primary endpoint is a laboratory measure. Finally, the results concern a short-term pharmacodynamic endpoint; the record does not report clinical outcomes that would establish the relevance of the observed laboratory changes to longer-term health.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacodynamic Effects of a Free-Fatty Acid Formulation of Omega-3 Pentaenoic Acid in Adults With Hypertriglyceridemia — NCT04177680.
• Registry record last updated 2022-03-04; status last verified 2022-02.
• Results first posted 2022-03-04.
• 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

NCT04177680, the ENHANCE-IT trial, was a completed phase 2 randomized, unmasked crossover study sponsored by Matinas BioPharma Nanotechnologies, Inc. It enrolled 100 adults with hypertriglyceridemia and compared MAT9001 with icosapent ethyl. Both interventions were described as 2g capsules taken twice daily with meals.

The primary outcome was median percent change in plasma triglycerides from baseline to 28 days. The primary population included participants with measurable results who received both drugs. The posted median was -20.9 for MAT9001 and -18.3 for icosapent ethyl, with 94 participants recorded for each treatment result. A direct comparative estimate and inferential test are not reported in the registry record.

The record lists four secondary outcomes involving lipids, apolipoproteins, PCSK9, hs-CRP, and omega-3 fatty acid concentrations. It reports zero serious adverse events and zero deaths in both groups, alongside other adverse events affecting 43 participants in the MAT9001 group and 28 in the icosapent ethyl group. Details of the comparative analysis, missing-data handling, and multiplicity approach are not reported.