Pharmacokinetics and Hepatic Safety of EGCG: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics and Hepatic Safety of EGCG (NCT04177693), a randomized phase 1 study. The primary outcome is Changes in Epigallocatechin Gallate (EGCG).

2. Clinical Question

3. Trial Design

This was a randomized, phase 1, parallel-group trial with no masking. The registry lists an enrollment of 39 and identifies Yale University as the sponsor. The study status is completed. The registry dates are 2020-11-24 for study start and 2022-01-31 for primary completion. These design details establish the broad structure of the study, but they do not describe all procedures that would be needed to evaluate the analysis in depth.

The three described arms received EGCG daily alone, EGCG with clomiphene citrate, or EGCG with letrozole. The combinations are therefore active regimens containing EGCG, rather than comparisons with a group receiving neither EGCG nor the accompanying medication. The arms are described as parallel groups, so the posted comparison is between groups rather than a crossover comparison within the same participants.

The trial summary describes an assessment of EGCG pharmacokinetics and hepatic safety in women with and without uterine fibroids. The registry record does not report how participants were distributed across the fibroid groups, whether randomization was stratified by fibroid status, or whether results were analyzed separately by that status. It also does not report details of the randomization sequence, allocation concealment, eligibility criteria, or blinding of laboratory assessment.

The primary endpoint is a change in EGCG concentration between baseline and the end-of-study visit, up to 40 days. The primary results are reported as medians, with an intended inter-quartile range measure, and the three groups are assessed using a Kruskal-Wallis test. The registry record does not report a detailed statistical analysis plan, a sample-size justification, or a participant-flow explanation connecting enrollment with the outcome-specific analysis counts. Those omissions limit what can be concluded about design choices and the extent to which the posted analysis followed a prespecified plan.

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

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 Changes in Epigallocatechin Gallate (EGCG), measured over Baseline, and Visit 4 (end of study, up to 40 days).

The primary outcome is change in epigallocatechin gallate (EGCG) concentration, measured in nM, from Visit 1 to Visit 4. Visit 4 is described as the end-of-study visit, up to 40 days. At both visits, the concentration measured 1 hour after taking study medication was used. The endpoint therefore focuses on the change between two post-dose measurements, rather than on a concentration measured at an unspecified time after dosing.

Pharmacokinetic measurements describe how drug or supplement concentrations behave in the body. In this trial, the concentration change is relevant to the stated question of whether EGCG exposure differs when EGCG is taken alone or alongside either of the other medications. The endpoint is also distinct from the hepatic laboratory outcomes: a change in EGCG concentration is not itself a measure of liver injury or hepatic safety.

The registry specifies the median as the summary parameter and the inter-quartile range as the dispersion measure. The posted group summaries give medians of 5.8 for EGCG daily alone, 256.3 for EGCG with clomiphene citrate, and 86.4 for EGCG with letrozole. The corresponding outcome counts are 12, 10, and 8. The record does not provide the inter-quartile range values in the posted primary summaries. It reports a three-group Kruskal-Wallis p-value of 0.112. That test addresses evidence of a distributional difference among the groups; the p-value does not quantify the size or clinical importance of a difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis uses a Kruskal-Wallis test to compare the three randomized groups. In general, this is a rank-based method for assessing whether observations across several independent groups appear to come from the same distribution. It is often useful when a comparison is framed around ranks or when a normal-theory comparison of means is not the selected approach. Its result is not a direct estimate of a difference in medians unless additional conditions about the distributions are appropriate. The registry reports the test name and p-value, but not the detailed assumptions or supporting diagnostic checks.

What does the primary p-value address?

In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the analysis assumptions were correct. For the primary outcome, the reported p-value is 0.112 for the three-group Kruskal-Wallis analysis. It is an overall test: it does not say which pair of groups differs, estimate a pairwise difference, or show the size of any group effect. The registry record does not report post-hoc comparisons for the primary endpoint. It also does not state a prespecified significance threshold or describe whether the test was planned as the sole primary analysis.

A p-value is not the probability that the null hypothesis is true. It is also not a measure of the clinical importance of a result. A p-value above a decision threshold may reflect a small underlying difference, substantial variability, limited information, or some combination; the posted result alone cannot distinguish those explanations. Conversely, a p-value below a threshold would not by itself establish that a difference is important. For a fuller interpretation, effect estimates and measures of uncertainty are needed alongside the test result.

How should medians and ranges be read?

In general, a median is the middle observation after the data are ordered. It can be a useful description when a distribution is skewed or contains extreme values. An inter-quartile range describes the middle half of the observations and gives information about spread. The registry identifies the median and inter-quartile range as the primary summary and dispersion, but numerical inter-quartile ranges are not reported in the registry record. Without them, the reader cannot compare the within-group spread using the intended dispersion measure.

The primary record gives lower and upper values around each group estimate, but does not define them. Because their construction and interpretation are not reported, it would be inappropriate to assume they are confidence limits, prediction limits, or another particular interval. A confidence interval, in general, describes uncertainty around an estimate under a stated method and repeated-sampling interpretation. That general meaning cannot safely be assigned to bounds whose method is unspecified.

What do the secondary tests add?

The posted analyses for bilirubin, ALT/SGPT, and alkaline phosphatase also use Kruskal-Wallis tests to compare all three groups. Their reported p-values are 0.508, 0.237, and 0.327, respectively. These are overall tests, not separate sponsor-reported pairwise tests. The secondary summaries use means and standard deviations, while the reported overall tests are rank based. In general, a mean summarizes the arithmetic center and a standard deviation describes spread around that mean; those summaries do not reveal the full distribution or whether the distribution is symmetric.

Alongside those sponsor-reported overall tests, the posted recalculated pairwise comparisons use unadjusted estimates from summary statistics. In general, a mean difference compares two group means, and a confidence interval expresses uncertainty around that estimated difference under its method. These recalculations are not the same analysis as the overall Kruskal-Wallis test. They should be treated as supplementary, unadjusted comparisons, not as replacements for the sponsor’s reported analysis. The registry record does not report whether the trial’s own analysis included pairwise comparisons or how any such comparisons were handled.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a model expects. When an analysis assumes less variability than the data contain, its uncertainty estimates can be too small and its tests can appear more decisive than warranted. When variability is large relative to the group differences, precision is reduced. The registry does not report a formal assessment of over-dispersion for the primary outcome, and the reported rank-based analysis does not give a model-based variance estimate in the posted record. It is therefore appropriate to discuss variability as a general statistical consideration, not to claim that over-dispersion was present in this trial.

The secondary recalculations include planning illustrations based on observed effects. In general, such illustrations show how a hypothetical future comparison’s sample size might vary under selected assumptions about the effect and analysis. They are not observed power for this completed trial, and they do not establish that the original design had adequate power. The record describes the illustrations as using a two-sided significance level of 0.05, equal allocation, and a normal approximation. Those assumptions belong to the illustration and should not be attributed to the trial’s original design, whose sample-size justification is not reported in the registry record.

Finally, a valid statistical interpretation depends on more than naming a test. The statistical plan, analysis population, handling of missing measurements, timing rules, and multiplicity approach can affect which results are considered primary and how uncertainty is assessed. Those details are not reported in the registry record. The available test results are therefore best read as summaries of the analyses that are posted, with the limits of those unreported methods kept in view.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a Kruskal-Wallis test across the three groups, with p = 0.112. The overall analyses for total bilirubin, ALT/SGPT, and alkaline phosphatase are also reported as Kruskal-Wallis tests, with p-values of 0.508, 0.237, and 0.327. These are the registry’s reported analyses and should be distinguished from the supplementary pairwise recalculations based on posted summary statistics.

In general, an overall three-group test asks whether the group distributions show evidence of an overall difference; it does not estimate each pairwise contrast. The recalculated secondary comparisons instead estimate unadjusted differences between EGCG alone and each combination group. They use summary statistics, so they may not reproduce the sponsor’s analysis method or account for features of the underlying participant-level data. Their confidence intervals and p-values are supplementary, not a substitute for the reported analysis.

The registry record does not report a pairwise primary analysis or a detailed statistical plan that would explain how the reported tests relate to any planned contrasts. It also does not report the sponsor’s analysis code or participant-level data. The reported primary test therefore remains the main basis for describing the posted primary result, while recalculated comparisons can be read only as additional, unadjusted context. No discrepancy between the sponsor’s analysis and a recalculation is identified in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates more than one outcome, group contrast, time point, or analysis. In general, as the number of statistical tests grows, the chance of at least one result appearing noteworthy by chance can increase. Researchers may address this through a prespecified hierarchy, an adjustment, or a clearly exploratory interpretation. The registry record lists 11 outcome measures and 11 analyses, including a primary outcome and several secondary outcomes. A multiplicity strategy, adjustment, or testing hierarchy is not reported in the registry record.

This matters particularly for the secondary outcomes. The registry reports three overall secondary tests and includes recalculated pairwise comparisons for those outcomes. The recalculated comparisons are unadjusted. They should not be interpreted as if they were a single planned test, and a nominal result from one comparison would require caution when considered alongside the wider set of outcomes and contrasts. The record does not clarify which secondary analyses were prespecified, whether any were considered exploratory, or whether other analyses were conducted but not posted.

The registry record does not report a missing-data method, the analysis population for each outcome, or a participant-flow account explaining why endpoint counts differ from the enrollment figure. Primary outcome counts are 12, 10, and 8 across the three groups. The posted secondary summaries use counts of 15, 11, and 12. These differences show that the number of observations contributing to a summary depends on the endpoint, but the reasons are not reported in the registry record. It is not possible to infer whether the differences reflect missing measurements, endpoint eligibility, exclusions, or another cause.

The record also does not report how missing measurements were handled, whether analyses used all randomized participants, or whether any sensitivity analyses assessed the effect of missing data. In general, missingness can affect results when the chance of a measurement being unavailable is related to a participant’s outcome or group. Without the missing-data rules and the analysis population, readers cannot evaluate that possibility or determine how robust the estimates are to alternative assumptions.

Likewise, the registry record does not report interim analyses, stopping rules, or a sample-size justification. These details should not be inferred from the posted outcome counts or from planning illustrations based on observed effects. The absence of these details does not prove that no such procedures existed; it means they are not reported in the registry record. This leaves uncertainty about the planned statistical framework and how completely the posted results represent it.

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 non-serious adverse event terms

The registry reports no serious adverse events in any of the three groups. The number at risk for serious adverse events is 16 for EGCG daily alone, 11 for EGCG with clomiphene citrate, and 12 for EGCG with letrozole. Deaths are reported as 0 in each group. The registry lists no serious adverse event terms.

These are observed counts, not proof that serious events cannot occur or that the groups have the same safety profile. The groups are small, and the record does not report follow-up duration for the adverse event summaries or the criteria used to classify events. The serious-event denominators also differ from the primary outcome counts, and the record does not explain the difference. No conclusion about comparative risk can be drawn from zero serious events alone.

The registry separately reports other, non-serious adverse events affecting 2 participants in the EGCG-alone group, 4 in the clomiphene group, and 6 in the letrozole group. These counts do not identify event types or severity beyond the registry’s category, and they should not be combined with the serious-event counts. The safety figures describe what was recorded in this trial; they do not establish that a regimen is safe or unsafe in other settings.

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

The posted primary analysis addresses whether changes in EGCG concentration differ across three randomized groups: EGCG daily alone, EGCG with clomiphene citrate, and EGCG with letrozole. The group medians differ numerically, but the overall Kruskal-Wallis test has p = 0.112. Taken together, the posted result does not establish a clear between-group difference in the primary endpoint. It also does not demonstrate that the groups have identical concentration changes.

The primary endpoint is a pharmacokinetic measure based on concentrations taken 1 hour after study medication at baseline and Visit 4. It does not directly measure a clinical outcome, and it should not be interpreted as showing whether a treatment improves a health condition. The trial summary also describes hepatic safety, but the primary endpoint is not a liver test. The separate hepatic laboratory results and adverse-event counts provide additional observations, with their own limitations.

The result does not settle whether any differences might exist in a larger or differently designed study. The primary outcome counts are 12, 10, and 8, and the registry does not report the planned sample-size justification, inter-quartile ranges, a detailed analysis plan, or a missing-data method. These limits mean that precision and robustness cannot be fully assessed from the registry record. The reported p-value is not a substitute for an effect estimate with well-defined uncertainty.

The result also does not establish that the combinations have the same effects as EGCG alone, that the accompanying medications have no influence, or that any group is superior. The posted primary test is an overall comparison, not a set of planned pairwise tests. The registry record does not report a primary pairwise analysis. The evidence therefore supports a measured description of the observed data and the reported test, not a broader claim of equivalence, benefit, or harm.

For the secondary outcomes, the posted tests likewise do not establish a clear group difference. Their interpretation is further limited by multiple outcomes, unadjusted recalculations, and missing numerical results for several listed secondary measures. The most defensible reading is that the registry records a small randomized study with an inconclusive primary comparison and limited information for assessing precision, safety, and the full set of planned analyses.

14. Why This Trial Matters Statistically

This trial is statistically useful because its primary question concerns measured concentration change across three randomized groups, while its reported primary method is a rank-based overall test. That combination illustrates why the choice of summary and test matters: the median describes a group’s center, while the Kruskal-Wallis test evaluates an overall distributional contrast. Neither alone provides all the information needed to describe the size and precision of each group difference.

It also highlights the distinction between an overall test and pairwise comparisons. A three-group test can address whether there is evidence of an overall difference without identifying which groups differ or estimating the contrast between any particular pair. The registry reports the overall test but not a primary pairwise analysis. This distinction is important when readers are tempted to compare the displayed group medians informally.

The study also includes pharmacokinetic, hepatic laboratory, and other secondary outcomes. Each has a different interpretation, and multiple outcomes increase the importance of a prespecified analysis strategy. The record’s lack of reported multiplicity handling, analysis populations, and missing-data procedures makes it difficult to evaluate how the full set of results was intended to be interpreted. That is a general lesson in reading registry results: a list of endpoint names and p-values does not replace the statistical plan.

Finally, the registry record demonstrates why a non-significant test should not be translated into evidence of no difference. A result can be inconclusive because of limited information or variability, and a p-value does not quantify the range of effects compatible with the data. Here, the outcome counts are small and the primary inter-quartile ranges are not reported. Careful description of what is known—and what remains unreported—helps prevent stronger claims than the posted evidence supports.

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 primary endpoint summaries do not include numerical inter-quartile ranges, although the registry identifies that measure as the intended dispersion. The lower and upper values reported alongside the primary medians are not defined in the registry record. As a result, the uncertainty around the primary group summaries cannot be interpreted confidently from those bounds alone.

Outcome counts differ between the primary and secondary summaries, and the adverse-event denominators also differ. The registry record does not explain these differences or describe the analysis population for each endpoint. It does not report the handling of missing measurements, exclusions, or sensitivity analyses. These gaps limit assessment of whether the observed results could depend on which participants contributed data.

The trial is described as including women with and without uterine fibroids, but the registry does not report their distribution across groups or outcome results by fibroid status. It also does not provide the details needed to assess randomization procedures, allocation concealment, adherence, or whether laboratory assessment was blinded. No separate untreated or placebo group is described; each arm received EGCG.

The sponsor-reported primary analysis is an overall Kruskal-Wallis test, while the registry does not report a primary pairwise analysis, a detailed statistical plan, or a sample-size justification. The registry lists multiple outcomes, but does not report a multiplicity strategy. Numerical results are not reported for several listed secondary outcomes. These limitations do not invalidate the posted observations, but they constrain how broadly the results can be interpreted and how precisely group differences can be assessed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetics and Hepatic Safety of EGCG — NCT04177693.
• Registry record last updated 2023-06-05; status last verified 2023-05.
• Results first posted 2023-06-05.
• 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

The registry describes a completed randomized, unmasked, parallel phase 1 trial sponsored by Yale University, with enrollment of 39. It assessed EGCG daily alone and EGCG combined with clomiphene citrate or letrozole in women with and without uterine fibroids. The primary endpoint was change in EGCG concentration from Visit 1 to Visit 4, up to 40 days, using measurements taken 1 hour after study medication.

The primary group medians were 5.8, 256.3, and 86.4, with outcome counts of 12, 10, and 8. The reported three-group Kruskal-Wallis p-value was 0.112. The registry also reports overall analyses for three hepatic laboratory outcomes, while numerical results for other listed secondary outcomes are not reported in the registry record.

Important details—including the sample-size justification, missing-data handling, analysis populations, and multiplicity strategy—are not reported in the registry record. The posted findings describe the observed data but do not establish equivalence or a clinical benefit or harm.