Pharmacokinetics of Centella Asiatica in the Elderly: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics of Centella Asiatica in the Elderly (NCT03929250), a randomized early/phase 1 study. The primary outcome is Maximum Human Plasma Concentration of Bioactives From Centella Asiatica..

2. Clinical Question

This is a pharmacokinetic question: it concerns the concentrations of compounds in plasma over time after oral administration, rather than a clinical benefit. The registry says that the compounds of interest include triterpenes, caffeoylquinic acids, and their metabolites. Blood samples were planned at specified times during the 12-hour period to generate a pharmacokinetic curve and estimate maximum concentration and area under the curve for each dose.

The crossover arrangement means the two dose conditions were scheduled as separate exposure periods, with the order randomized. The stated sequences were 2g followed by 4g, or 4g followed by 2g, with a minimum washout period of 2 weeks between doses. The record does not report participant-level concentration values or an estimate of the difference between doses. It therefore does not answer whether the measured maximum concentration was higher after either dose, how large any difference was, or how precisely the comparison was estimated.

3. Trial Design

The registry identifies this as a completed EARLY PHASE1 study with randomized allocation, double masking, and a crossover model. Enrollment was 8. The sponsor was Oregon Health and Science University. The recorded study start was 2019-07-05 and primary completion was 2019-11-30.

Two dose conditions were studied: a single dose of a product containing 2g of Centella asiatica water extract and a single dose of a product containing 4g. In one sequence, the 2g dose came first and the 4g dose followed after a minimum washout period of 2 weeks. In the other sequence, the order was reversed. Randomizing the order can help prevent systematic differences in sequence from being mistaken for dose effects, while a crossover design allows measurements under both conditions within a participant. These are general design principles; the record does not describe the allocation procedure or how sequence effects were handled in the analysis.

Double masking indicates that masking was recorded, but the identities of the masked parties and the procedures used to maintain masking are not reported in the registry record. Details about eligibility criteria, setting, adherence, protocol deviations, and the exact conduct of the washout are also not reported.

The study was designed to measure oral bioavailability and pharmacokinetics of bioactive compounds from the extract product in cognitively healthy elders. The registry describes blood sampling over a 12-hour period and says that high performance liquid chromatography tandem mass spectrometry would be used to measure plasma concentrations. It also lists secondary outcomes concerning urinary excretion, vital signs, body mass index, and electrocardiography. The record does not provide results for those outcomes or describe a statistical analysis 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

Reasons for not completing this period:

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 Maximum Human Plasma Concentration of Bioactives From Centella Asiatica., measured over A 12-hour post-administration period (15, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, and 720 minutes)..

The primary outcome is maximum human plasma concentration of bioactive compounds from Centella asiatica. It is described as a continuous measure summarized by a mean and standard error, with units of ng/mL. Measurements were planned over a 12-hour post-administration period, at the sampling times specified in the registry. The compounds include triterpenes, caffeoylquinic acids, and their metabolites.

Maximum concentration is a pharmacokinetic measure of the highest measured plasma concentration after administration. In general, it helps describe the peak level reached during the observation period. It does not, by itself, describe the full concentration-time profile or the total exposure over time. The registry also says that area under the curve was to be determined for each dose, but it does not report those results.

The planned laboratory method was high performance liquid chromatography tandem mass spectrometry. The record describes generating a pharmacokinetic curve from blood samples and determining pharmacokinetic parameters for both dose conditions. This endpoint is relevant to the stated objective of characterizing oral bioavailability and pharmacokinetics. It is not a direct measure of a health outcome or clinical benefit.

The registry record does not report numerical maximum concentrations, standard errors, participant-level results, or an estimated comparison between doses. It also does not reduce the primary outcome to one result: the record notes multiple categories or time points, so it is not represented as a single comparison. Without the posted outcome values and their analysis, the magnitude and precision of any dose contrast cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design contribute?

In a crossover study, participants receive more than one intervention condition in a planned sequence. This study scheduled each participant to receive both the 2g and 4g doses, with the order randomized and a minimum washout period of 2 weeks between doses. In general, comparing conditions within the same participant can reduce the influence of stable differences between people, because those characteristics are shared across that participant's exposure periods.

A crossover design also requires attention to the order and timing of observations. A period effect is a difference associated with when an exposure occurs, while a sequence effect is associated with the order in which conditions are received. Carryover refers generally to an effect of an earlier exposure that remains relevant during a later period. Washout is intended to separate exposure periods, but the registry's stated minimum washout does not by itself establish whether carryover was assessed or how it was handled. The statistical methods for sequence, period, and carryover are not reported in the registry record.

What is being measured over time?

The primary outcome concerns plasma concentrations of several bioactive compounds and metabolites after administration. The registry describes blood sampling at multiple specified times during a 12-hour post-administration period. In general, these repeated measurements form a concentration-time profile. A maximum concentration focuses on the highest measured value in the profile; area under the curve summarizes exposure across the observation period. These measures answer related but distinct pharmacokinetic questions.

The stated laboratory method is high performance liquid chromatography tandem mass spectrometry. The registry does not report assay validation, limits of quantification, handling of concentrations below an assay limit, or the specific rules for deriving each parameter. Such details can affect how measurements are summarized, but no further method should be inferred from the registry description.

How should means and standard errors be understood?

The primary outcome is described as a mean with standard error. In general, a mean is a summary of the observed values, while the standard error expresses uncertainty about the estimated mean under a statistical model. It does not describe the range or variability among individual values in the way a standard deviation would. A confidence interval, when reported, gives a range of values compatible with the data and model at a stated confidence level. The registry does not report confidence intervals, means, or standard errors for the primary outcome.

Concentrations and pharmacokinetic parameters can have skewed distributions. General analysis choices may therefore include transformations or other methods suited to the distribution, but the registry record does not state whether any such approach was used. It also does not report a model, test statistic, confidence level, or method for handling repeated measurements.

Why does the endpoint have multiple dimensions?

The primary outcome description includes several compound categories, metabolites, and sampling times, and the registry notes that it was not reduced to one comparison. In general, testing or estimating many outcomes can create multiplicity: the more separate questions considered, the greater the chance that an apparently notable finding may occur by chance when there is no corresponding underlying effect. The impact depends on which questions were prespecified and how they were analyzed. The registry does not report a multiplicity strategy or identify a single concentration comparison as the sole inferential result.

The registry lists 11 outcome measures and 0 analyses. Those record entries do not explain which outcome data were collected, which analyses were conducted outside the registry, or how many separate tests may have been considered. The analysis plan and any adjustment for multiple comparisons are not reported in the registry record.

What can a planning illustration tell a reader?

General sample-size illustrations use assumptions about significance level, allocation, the effect to detect, and a statistical approximation. The registry's stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The record describes these as planning illustrations based on an observed effect, not the trial's own design. Such illustrations are prospective planning aids, not observed power and not evidence that the study detected an effect. The record does not report the trial's own sample-size justification.

Interpretation of a planning illustration also depends on whether its assumptions match the intended future design and analysis. For a crossover study, a planning calculation may need assumptions that reflect within-participant variability and correlation. Those details are not reported in the registry record. No conclusion about the adequacy of the enrolled sample or the precision of the primary comparison can be drawn from the design description alone.

What analysis details remain unknown?

The registry record does not report the primary outcome results, the analysis population, missing-data methods, or the statistical model. It also does not say whether the planned analysis used participant-level paired comparisons, how measurements from different compounds were combined or kept separate, or how repeated sampling times were handled. These are general decisions that can affect estimates and uncertainty. Without the analysis details and results, a reader cannot reproduce or appraise the primary comparison from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is not a single simple measurement in the registry description. It includes multiple bioactive compounds and metabolites measured at multiple times, and the registry notes that it was not reduced to one comparison. The record also lists 11 outcome measures, including secondary outcomes for urinary excretion, oral temperature, pulse rate, seated systolic and diastolic blood pressure, body mass index, and participants with change in electrocardiography.

In general, multiplicity arises when several outcomes, time points, or comparisons are examined. If many tests are performed, the chance of at least one apparently notable result can rise. Researchers may address this by prespecifying a primary contrast, adjusting for multiple testing, or emphasizing estimation and uncertainty rather than treating each test as a separate confirmatory finding. The registry record does not report a multiplicity plan, a hierarchy among the several primary outcome components, or which comparisons were prespecified for inference.

The registry reports 0 analyses. It does not report primary outcome values, a statistical analysis plan, or results for the listed secondary outcomes. The record also does not state how missing blood samples or other incomplete measurements were handled, whether anyone was excluded from an analysis, or which analysis population was used. These are not evidence that data were missing or that analyses were omitted in practice; their status is not reported in the registry record.

In general, missingness can affect interpretation when the availability of measurements is related to dose, participant characteristics, or the measurement itself. An analysis population describes which participants or observations are included in a particular estimate. Without reported missing-data and population details, the completeness and applicability of any result cannot be assessed. The record's enrollment count alone does not establish the number of observations used for each outcome.

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 registry reports serious adverse events separately for the 2g and 4g dose conditions. For each condition, 8 were listed as at risk, 0 serious adverse events were reported, and 0 deaths were reported. For other adverse events, 4 were reported for each condition, with 8 listed as at risk in each condition.

These are the registry's dose-specific entries. They should be read as reported counts, not as estimates of comparative risk. The crossover design means the dose conditions are exposure periods within sequences; the entries do not establish that the groups are independent. The record does not clarify whether the same participant contributed an other adverse event during both dose periods, how events were defined, or the observation window used for adverse-event reporting.

In general, a zero count of serious events in a small study does not establish that the risk is absent. It indicates only that no serious events were recorded in the listed condition in this registry entry. The adverse-event figures also do not describe event severity beyond the serious versus other categories, timing, relatedness to the product, or participant-level patterns. Those details are not reported in the registry record.

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

The registry record documents a completed randomized, double-masked crossover pharmacokinetic study of 2g and 4g Centella asiatica water extract product doses in cognitively healthy elders. It describes the planned measurement of plasma bioactive compounds over a 12-hour period and the intended estimation of maximum concentration and area under the curve.

It does not report the primary outcome values or an estimated comparison between doses. Consequently, the record does not establish whether the concentrations differed, the direction or size of any difference, or the precision of an estimate. It also does not report the analysis method or results for the listed secondary outcomes. Completion status is administrative information and does not supply those missing findings.

Even if pharmacokinetic results were available, maximum plasma concentration would describe a concentration measure, not a clinical outcome. In general, a pharmacokinetic finding alone cannot establish a health benefit or harm. It also cannot establish that a particular dose should be used. No such conclusion is supported by the registry information recorded.

The study's enrollment of 8 and its early-phase designation describe the study record, but they do not by themselves indicate the precision of an unreported estimate. Precision depends on the observed data and analysis. The registry's adverse-event counts are limited to the categories and reporting detail recorded, and do not establish absence of risk.

The appropriate conclusion is therefore narrow: the registry describes a dose-comparison pharmacokinetic study and its planned measurements, but does not make the primary findings available for statistical interpretation. Claims about concentration differences, exposure, or clinical implications would require results and analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it combines a randomized dose order with a crossover design. In general, crossover studies can make efficient use of within-participant comparisons when each participant receives each condition. At the same time, interpretation depends on the sequencing, spacing, and analysis of the exposure periods. The registry gives the dose sequences and minimum washout period of 2 weeks, but does not report how period or carryover considerations entered the analysis.

The primary outcome also illustrates the distinction between a pharmacokinetic profile and a single endpoint. Several compounds and metabolites were to be measured at multiple sampling times, while maximum concentration and area under the curve were to be derived for each dose. A reader needs a clear definition of the comparison and the handling of these multiple components to understand what a reported result represents. Those analysis details are not reported in the registry record.

The record's stated mean and standard error indicate a plan to summarize a continuous measure, but no corresponding values or uncertainty estimates are reported. That absence matters: a trial's design can explain how evidence was intended to be generated, but it cannot substitute for observed estimates. Without results, neither effect size nor precision can be evaluated.

The study also shows why safety counts and pharmacokinetic results should be kept distinct. The registry lists adverse-event counts by dose condition, but those counts do not answer the primary concentration question. Conversely, an unreported pharmacokinetic comparison cannot be inferred from the adverse-event entries. Each result requires its own definition, observation data, and analysis.

Finally, the registry reports 0 analyses and does not report the statistical plan or missing-data methods. This limits reproducibility and makes it difficult to judge how the planned comparisons were translated into estimates. The statistical value of the record is therefore chiefly in its description of the intended design and questions, rather than in evidence about the observed dose contrast.

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 most important limitation for interpreting the primary endpoint is that the registry record does not report its results. There are no recorded maximum plasma concentration estimates, standard errors, area-under-the-curve estimates, or dose-comparison results. The record also states that the primary outcome has several categories or time points and was not reduced to one comparison, leaving the specific inferential contrast unclear.

Enrollment was 8. This is a description of the study record, not a calculation of precision or a basis for assuming a particular level of statistical power. Participant-level observations, the number of evaluable measurements, and the analysis population are not reported. Missing-data handling, exclusions, and protocol deviations are also not reported in the registry record.

The crossover design makes sequence, period, and carryover considerations relevant in general. The registry describes randomized order and a minimum washout period of 2 weeks, but does not report whether these effects were assessed, what model was used, or whether the washout was adequate for the compounds measured. No further conclusion about those design features can be drawn from the record.

The record identifies the primary summary as a mean with standard error but does not provide a confidence interval or other measure of uncertainty. It does not report the statistical analysis plan, multiplicity handling, laboratory assay performance details, or the relation of the findings to any clinical outcome. The adverse-event entries also lack detail on definitions, timing, relatedness, and participant-level overlap across dose periods.

These limitations mean the registry supports description of the study design and intended measurements, but not a quantitative interpretation of the primary result or a broader clinical conclusion.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetics of Centella Asiatica in the Elderly — NCT03929250.
• Registry record last updated 2025-08-06; status last verified 2025-07.
• Results first posted 2025-08-06.
• 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

NCT03929250, “Pharmacokinetics of Centella Asiatica in the Elderly,” is recorded as a completed EARLY PHASE1 study sponsored by Oregon Health and Science University. It used randomized allocation, double masking, and a crossover model, with enrollment of 8. The recorded study start was 2019-07-05 and primary completion was 2019-11-30.

Participants were scheduled to receive single doses of 2g and 4g Centella asiatica water extract product in randomized order, separated by a minimum washout period of 2 weeks. The primary outcome concerned maximum plasma concentration of bioactive compounds over a 12-hour period. The registry describes blood sampling and laboratory measurement but does not report primary outcome results or an analysis.

Secondary outcomes include urinary excretion, vital signs, body mass index, and electrocardiography. The registry also reports dose-specific adverse-event counts. Statistical analysis details, missing-data methods, and the analysis population are not reported in the registry record.