A Clinical Trial of Epizon-701 (EPN-701) in Subjects With End-Stage Renal Disease (ESRD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Trial of Epizon-701 (EPN-701) in Subjects With End-Stage Renal Disease (ESRD) (NCT05285787), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events (AEs).

2. Clinical Question

The study also set out to examine EPN-701 pharmacokinetics and changes in circulating biomarkers. The stated rationale concerns vascular calcification in end-stage renal disease and the role of vitamin K2-related biomarkers. Those background considerations explain why the investigators studied the compound, but they are not themselves findings from this trial.

Because there was no control group, the central clinical question is descriptive: what safety events were recorded among participants exposed to EPN-701 during the study period? The design does not directly compare event rates with usual care, placebo, or another treatment. It also cannot isolate the effect of EPN-701 from other explanations for events observed in this population.

3. Trial Design

This was a completed Phase 2, prospective, single-group study sponsored by Epizon Pharma, Inc. The registry lists 18 participants and a single arm receiving EPN-701 orally at 10mg daily over 14 days. The study was unmasked, and allocation is listed as not applicable. There was no concurrent comparison arm.

The registry describes the study as assessing safety and tolerability, pharmacokinetics, and surrogate biomarkers as proxies for efficacy in people with stable end-stage renal disease receiving outpatient hemodialysis. The brief summary specifies daily oral administration for 14 days. The primary endpoint timeframe extends through study completion, over the 14-day treatment period and a one-week follow-up period.

The primary outcome is the number of participants with adverse events. The safety population is defined as all patients who received at least one dose of EPN-701. Secondary outcomes include plasma concentrations of EPN-701 and time to maximum plasma concentration. The registry lists seven outcome measures, but detailed results for the secondary outcomes are not reported in the registry record.

The study started on 2019-03-01, reached primary completion on 2021-04-30, and is listed as completed. The registry record does not report the rationale for the enrollment target, recruitment details, or a statistical analysis plan. Since the study has no randomized comparison, differences between treatment groups are not an estimand that this design can address.

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 patients who received at least one dose of EPN-701 was included in the safety evaluation.

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 Number of Participants With Adverse Events (AEs), measured over Through study completion; over 14 days treatment and one week follow up..

The primary endpoint counts participants with adverse events during the study’s defined safety observation period. The registry description includes treatment-emergent adverse events, events assessed as related to study drug, serious adverse events, and deaths. The outcome is a count of participants, rather than a measure of symptom severity, duration, or change in a laboratory value.

Safety endpoints are used to describe the kinds and frequency of events observed during exposure and follow-up. They can help characterize tolerability in the studied population and identify events that warrant further assessment. An event’s occurrence during a trial does not by itself establish that the study drug caused it. The registry distinguishes events assessed as related to the study drug, but the process and criteria used for that assessment are not reported in the registry record.

The endpoint is descriptive in this single-group study. Without a control group, the recorded count cannot be directly compared with what would have occurred in similar participants without EPN-701. The observation period is also limited to treatment and the specified follow-up, so the endpoint does not describe safety beyond that period.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpretation begins with the design. A single-group study follows participants receiving the intervention but lacks a concurrent control group. Its event counts can describe what occurred among exposed participants; they cannot directly measure how those outcomes compare with an alternative treatment or no study treatment. The registry lists no masking and no randomized allocation, so neither blinded treatment assignment nor randomization between groups is part of this design.

What does a participant count represent?

A participant count records how many people met the outcome definition. Here, the primary outcome is expressed as the number of participants with adverse events, and the safety population consists of patients who received at least one dose. Counts are useful for showing the scale of observed events in the enrolled group. They are not, on their own, an estimate of a causal treatment effect.

Counts also depend on how events are defined, collected, grouped, and attributed. The registry description includes treatment-emergent events, events assessed as related to study drug, serious adverse events, and deaths. However, the detailed operational definitions and event-assessment procedures are not reported in the registry record. Without those details, readers should avoid assuming that the categories are mutually exclusive or that an event’s timing proves its cause.

How should percentages and uncertainty be understood?

A percentage expresses a count relative to a stated denominator. The serious-event and other-event counts are each reported with 18 participants at risk. The listed serious terms are each reported as 5.6%. These are descriptive summaries of the enrolled group, not comparisons with a control group. A confidence interval, when reported, describes uncertainty around an estimate under the assumptions of the method used. Confidence intervals for these safety counts are not reported in the registry record.

With a small group, uncommon outcomes may not be observed even if they could occur in a larger population. Conversely, observing an event does not demonstrate that the intervention caused it. Both points matter when interpreting a study with limited enrollment and no comparator. The registry record does not report a formal inferential analysis for the primary endpoint.

What can the pharmacokinetic outcomes address?

Pharmacokinetic outcomes describe drug concentrations over time. Plasma concentration can characterize measured exposure, while time to maximum plasma concentration describes when the highest measured concentration occurs. These outcomes are distinct from clinical efficacy and from the adverse-event count. Although they are listed as secondary outcomes, their detailed results are not reported in the registry record.

The study also describes circulating biomarkers as surrogate measures or proxies for efficacy. A biomarker can provide biological information, but a change in a surrogate does not by itself demonstrate a change in a clinical outcome. The registry record does not report the detailed biomarker results or an analysis linking biomarker changes to clinical events. The stated rationale and study aims should therefore be distinguished from findings.

How should planning illustrations be read?

Any sample-size planning illustrations associated with the posted results are not the trial’s original design justification. They are described as hypothetical calculations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The calculation varies the fraction of the observed effect to be detected. These assumptions describe a planning exercise, not what happened in this single-group study.

In particular, the hypothetical two-arm allocation does not turn the actual study into a controlled comparison. A sample-size illustration is not observed power, and it does not establish the probability that the study detected a real effect. The registry record does not report the original sample-size justification or a protocol-based power calculation. Any planning result should be treated as a hypothetical design aid, separate from the observed participant counts.

Why do event distributions matter?

Statistical methods should match the outcome and design. For a binary event outcome, the basic information is the number experiencing the event and the number included in the relevant safety population. Comparative methods require a comparison that this study does not have. Repeated measurements, such as plasma concentrations over time, would require attention to their timing and within-participant structure, but the registry record does not report the analysis methods used for those outcomes.

When outcomes are counts of recurrent events rather than participants with any event, methods may need to account for over-dispersion: variability greater than a simple model assumes. That is a general statistical consideration, not a reported feature of this trial’s primary endpoint. The primary endpoint is described as a number of participants with events, and the registry record does not report recurrent-event modeling or other model details.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("EPN-701 Treatment Arm")
n      <- c(18)
events <- c(8)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  EPN-701 Treatment Arm  18  8  44.4  21.5  69.2  24.6  66.3  24.4  66.5

11. Multiplicity, Missing Data and Analysis Populations

The study lists a primary safety outcome and secondary pharmacokinetic outcomes, along with a total of seven outcome measures. When a study evaluates multiple outcomes, the chance of at least one apparently notable result can increase if many tests are performed. Statistical plans may address this through a prespecified outcome hierarchy or multiplicity adjustment. Such procedures are not reported in the registry record, so the handling of multiple outcomes cannot be assessed.

The registry record lists no analysis entries. It does not report a prespecified statistical analysis plan, hypothesis tests for the primary outcome, or a multiplicity strategy. This absence does not show that no analyses were performed; it means the analysis details are not available in the registry record.

Missing-data handling is also not reported in the registry record. The safety population includes all patients who received at least one dose, but the record does not explain whether all such participants completed follow-up, how incomplete safety information was treated, or whether any outcome-specific data were unavailable. The enrollment figure alone does not establish that every participant contributed complete information for every outcome.

Analysis populations for pharmacokinetic and biomarker outcomes, including any rules for excluding measurements, are not reported in the registry record. These omissions limit assessment of whether the analyses followed prespecified rules and how incomplete observations may have affected the reported results.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cholelithiasis (5.6%), pseudoaneurysm of arteriovenous graft (5.6%).

The adverse-event record lists 2 participants with serious adverse events among 18 at risk and 8 participants with other adverse events among 18 at risk. It reports 0 deaths. The serious terms listed are cholelithiasis and pseudoaneurysm of arteriovenous graft, each at 5.6%.

These counts describe events recorded during the study’s safety observation period, which covers the 14-day treatment period and a one-week follow-up. They should not be read as proof that the study drug caused an event. The registry description includes events assessed as related to the study drug, but the available record does not give the event-by-event attribution or criteria used.

The serious and other event categories should not be added together to infer a total number of participants affected. The record does not specify whether participants could be counted in both categories, and it does not provide a participant-level breakdown. The listed percentages for the serious terms are descriptive and do not indicate a comparison with another group. Since there is no control group, these results do not provide a comparative estimate of safety.

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

The result establishes that the registry recorded serious adverse events in 2 participants, other adverse events in 8 participants, and no deaths among the stated safety group of 18 at risk. It also records cholelithiasis and pseudoaneurysm of arteriovenous graft as serious terms, each at 5.6%. These are observations from the study period, not estimates of what would happen under another treatment.

The trial does not establish whether EPN-701 caused any particular event. Events occurring after treatment may be related to treatment, underlying disease, other care, or other factors. The registry includes a category for events assessed as related to study drug, but the assessment details are not reported. Nor does the study’s uncontrolled design permit a direct comparison of event rates with an untreated or differently treated group.

The results do not establish efficacy. The stated study aims include pharmacokinetics and biomarker assessment, but detailed findings for these outcomes are not reported in the registry record. Even if a biomarker changed, a surrogate change would not by itself demonstrate a clinical benefit. The safety findings also do not establish long-term safety, because the reported observation window is limited to treatment and the specified follow-up.

The sample-size planning illustrations are hypothetical and should not be interpreted as observed power or as the study’s original design justification. The registry record does not report that original justification, the detailed statistical plan, or missing-data procedures. Taken together, the posted information supports a descriptive reading of safety events in this enrolled group, while leaving comparative effects, causal attribution, longer-term outcomes, and detailed pharmacokinetic or biomarker conclusions unresolved.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between describing outcomes and estimating comparative effects. A single-group study can document events observed during exposure and follow-up, but without a comparison group it cannot determine whether those events occurred more or less often than they would have under another strategy. That distinction is central when reading safety findings in a population with serious underlying illness.

The registry’s safety endpoint is based on participant counts, which are relatively direct to understand. Yet interpreting those counts still requires attention to the safety population, follow-up window, event definitions, and possible overlap among categories. The record specifies the population and timeframe, but does not report all operational and analysis details. That makes transparent reporting important for understanding exactly what the counts represent.

The trial also names pharmacokinetic and biomarker aims alongside safety. Those aims concern different kinds of evidence: measured drug exposure, biological indicators, and clinical events answer different questions. A biomarker may be scientifically informative without proving a patient-relevant effect. Keeping these evidence types distinct prevents a mechanistic rationale or an outcome aim from being mistaken for a result.

Finally, hypothetical sample-size planning must be separated from the actual study design. Illustrations based on a two-arm comparison do not supply a control group retrospectively, and they do not show that the study had a particular probability of detecting an effect. This is a useful example of why design assumptions, observed outcomes, and planning calculations should be interpreted as separate statistical quantities.

15. 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 main design limitation is the absence of a concurrent comparator. The registry lists a single group, no masking, and allocation as not applicable. Consequently, the recorded adverse events cannot be used to estimate a comparative treatment effect or to separate treatment effects from the background risks faced by participants with end-stage renal disease receiving hemodialysis.

Enrollment was 18, limiting the range of safety experience captured. Rare or delayed events may not appear in a group of this size or within the stated observation period. The safety timeframe covers treatment over 14 days and a one-week follow-up; outcomes beyond that period are not addressed by these counts.

The registry record does not report detailed event narratives, severity grading, timing by participant, or the criteria used to assess relationship to study drug. It also does not clarify overlap between serious and other adverse-event categories. These gaps constrain interpretation of the event totals and the listed serious terms.

Detailed results for the secondary pharmacokinetic outcomes and biomarker assessments are not reported in the registry record. The record also does not report the statistical analysis plan, missing-data methods, multiplicity procedures, or the original sample-size justification. These omissions make it difficult to assess the prespecification and completeness of outcome analyses. The hypothetical planning assumptions do not resolve those limitations or substitute for a controlled study design.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Clinical Trial of Epizon-701 (EPN-701) in Subjects With End-Stage Renal Disease (ESRD) — NCT05285787.
• Registry record last updated 2024-09-25; status last verified 2024-05.
• Results first posted 2024-09-25.
• 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.

19. Record Summary

NCT05285787 is a completed Phase 2 prospective study of EPN-701 (menaquinone-7; MK-7) in people with stable end-stage renal disease receiving outpatient hemodialysis. The registry lists 18 participants in a single, unmasked group receiving 10mg orally daily over 14 days. The primary outcome is the number of participants with adverse events, with the safety evaluation including patients who received at least one dose.

The posted safety results list 2 participants with serious adverse events, 8 with other adverse events, and 0 deaths among 18 at risk. Cholelithiasis and pseudoaneurysm of arteriovenous graft are each listed at 5.6%. The study started on 2019-03-01 and reached primary completion on 2021-04-30.

The record’s stated aims include pharmacokinetics and circulating biomarkers, but detailed results for those outcomes are not reported in the registry record. With no control group, the safety findings are descriptive and do not establish causation or comparative effects.