Comparing The PK Of Aramchol Meglumine Granules To Aramchol Free Acid Tablets: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparing The PK Of Aramchol Meglumine Granules To Aramchol Free Acid Tablets (NCT06502561), a randomized phase 1 study. The primary outcome is Cmax of Aramchol.

2. Clinical Question

The clinical question is about relative pharmacokinetics in healthy volunteers, not clinical benefit or safety in a patient population. The registered study title identifies a relative bioavailability comparison, while the primary endpoint is Cmax. The registry reports geometric means and geometric coefficients of variation for this endpoint. Its posted Cmax summaries are 3.334 µg/mL for 400 mg aramchol meglumine, 2.057 µg/mL for 200 mg aramchol meglumine, and 0.668 µg/mL for 300 mg aramchol free acid. These are descriptive summaries. The registry record does not report a primary-endpoint treatment contrast, confidence interval, or p-value, so the summaries alone do not establish the size or precision of a comparative effect.

The doses differ across the posted groups. Thus, the comparisons are not simply a contrast of two formulations at a common dose. The registry describes randomized treatment assignments in later periods but does not provide enough detail to reconstruct every participant’s treatment sequence from the posted descriptions.

3. Trial Design

This is a completed Phase 1, randomized, unmasked crossover study sponsored by Galmed Pharmaceuticals Ltd. It enrolled 16 healthy volunteers. The registry lists the study as starting on 2025-02-15, with primary completion on 2025-06-15. Its official title describes a relative bioavailability study of aramchol meglumine granules for oral suspension and aramchol free acid 300 mg tablets.

The registry describes a three-period schedule. All study subjects received a single 400 mg dose of aramchol meglumine in Period 1. In Period 2 and Period 3, subjects were randomized 1:1 to receive aramchol meglumine or the 300 mg aramchol free acid tablet, identified as the reference. The posted results also include a 200 mg aramchol meglumine group. The registry does not give a complete participant-level sequence or sufficient detail to determine from the record how the posted group sizes map to every period and randomized sequence.

In general, a crossover design compares treatments across periods within a study, rather than assigning every participant to only one treatment for the entire study. Such designs can account for some stable differences between participants, but interpretation may also depend on period, sequence, and carryover considerations. Those are general design considerations; the registry record does not report the detailed methods used to address them in this study.

The primary endpoint was Cmax, the observed maximal concentration after administration, measured in µg/mL. The record lists an 8 days timeframe and 19 blood samples in each study period, from within 10 minutes before dosing through 168 hours (Day 8) after dosing. The registry lists nine outcome measures and six secondary outcomes. It reports no analyses under the analyses listing, and a study-specific statistical analysis plan, washout details, and sample-size justification are not reported in the registry record.

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: A washout period of 74-95 days was implemented between Period 1 and Period 2. Another washout period of 14-15 days was implemented between randomization to Period 2 or Period 3 (Crossover parts)

Period 1- 400 mg AM- 8 Days

Period 2- 200 mg AM or 300 mg AA- 8 Days

Period 3- 300 mg AA or 200 mg AM- 8 Days

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Note that Baseline charactersitics were reported for each period using "per sequence" arm/group of the partcicpant flow, meaning that the actual number of subjects entering the study (i.e., Period 1) was 16. These subjects were then moved to Period 2 (i.e., 14), and 12 subjects were then moved to Period 3.

6. Primary Endpoint

The registry lists the primary outcome as Cmax of Aramchol, measured over 8 days 19 blood samples were drawn in each study period: within 10 minutes pre-dose and 2, 3, 4, 6, 8, 10, 12,14, 18, 24, 30, 36, 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144(Day 7), 168 hours (Day 8) post-dose..

Cmax is the observed maximal concentration of aramchol in blood after administration. It is used in pharmacokinetic evaluation because it describes the peak concentration reached during the sampling period. In a relative bioavailability study, comparing concentration measures across treatments can help characterize how the study formulations and doses differ in the concentration profiles observed after dosing. Cmax is only one part of that profile; it does not by itself describe the full amount or timing of exposure.

The registry reports Cmax as a geometric mean, with geometric coefficient of variation as its dispersion measure. A geometric mean is a summary suited to positive measurements that may be unevenly distributed, while the coefficient of variation conveys relative variability around the geometric mean. These are general interpretations of the statistics. The registry identifies the endpoint description as the observed maximal concentration after administration.

Blood sampling was scheduled across 8 days, with 19 samples in each study period. The schedule began within 10 minutes pre-dose and extended to 168 hours (Day 8) post-dose. Sampling over time is important for identifying a peak: a measurement taken too early or too late could miss the maximum. The listed schedule gives the planned observation times, but the record does not report the actual sampling completeness for each participant.

The posted group summaries are 3.334 µg/mL for 400 mg aramchol meglumine, 2.057 µg/mL for 200 mg aramchol meglumine, and 0.668 µg/mL for 300 mg aramchol free acid. The record does not post a comparative estimate or uncertainty interval for Cmax. Consequently, the endpoint summaries describe the observed groups but do not quantify the precision of a treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is Cmax, a continuous pharmacokinetic measure reported as a geometric mean with a geometric coefficient of variation. The geometric mean summarizes concentration values on a multiplicative scale, which can be useful when measurements are positive and variability is proportional to the level. The geometric coefficient of variation expresses relative dispersion rather than dispersion in the original measurement units. These are general statistical interpretations; the registry does not explain why these particular summaries were selected for the analysis.

The posted primary results give a geometric mean for each dose group, but no comparative estimate or confidence interval. A group summary answers what was observed within that group; a treatment contrast answers how two groups differ and how uncertain that estimated difference is. Without a reported primary contrast, it is not possible to use the registry results to assess the precision of a Cmax comparison. The record also does not report an inferential primary-endpoint analysis.

The listed secondary continuous outcomes use arithmetic means and standard deviations. A mean difference expresses the difference between two group means in the endpoint’s original units. A confidence interval gives a range of values compatible with the observed data under the assumptions of the calculation. A narrow interval indicates greater precision than a wide interval. If an interval includes zero, the data do not rule out a zero mean difference at the corresponding confidence level. That is not the same as demonstrating equivalence or proving no difference.

The posted pairwise estimates for selected secondary outcomes are recalculated, simple unadjusted comparisons from summary statistics. They are not reported sponsor analyses. Such calculations do not incorporate participant-level observations, and the registry’s posted summaries do not permit adjustment for period, sequence, or within-participant correlation. Those elements can be important in crossover analyses. This is a general limitation of reconstructing comparisons from group-level summaries; the study-specific statistical model is not reported in the registry record.

The p-values accompanying those recalculated comparisons are unadjusted. A p-value measures how unusual data at least as extreme as the observed data would be under a specified null model. It does not measure the probability that the null hypothesis is true, the magnitude of a clinically meaningful effect, or the chance that a finding will replicate. Because several secondary outcomes and comparisons are present, multiple testing is relevant: examining many results increases the chance of seeing a small p-value by chance. The registry does not report a multiplicity adjustment or confirmatory testing hierarchy.

Variation matters when estimating means and contrasts. Standard deviations describe spread in the original units; larger spread relative to the observed difference generally makes a comparison less precise. Over-dispersion is a general concern when outcome variability exceeds what an analysis model assumes. A model that understates variability can produce overly narrow intervals and overly small p-values. The record does not describe a variance model or report a study-specific assessment of over-dispersion, so no claim can be made about whether that issue was examined.

For a crossover study, observations from the same participant across periods are generally correlated. A within-participant analysis can use that pairing and may be more precise than treating all observations as independent. It also needs to account appropriately for period and sequence, and sometimes for carryover. These are general methods considerations, not a description of the analysis conducted in this trial. The registry record does not report whether the posted results used paired data or how period and sequence were handled.

The sample-size illustrations associated with the secondary comparisons are planning scenarios based on observed effects, not observed power and not the trial’s original design calculation. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect set to a stated fraction of the observed effect. In general, a planning calculation estimates how many participants might be needed under its assumptions to detect a specified effect. It does not show the probability that this completed trial detected an effect, and it does not establish that the assumed effect is a reliable target. The trial’s own sample-size justification is not reported in the registry record.

The posted secondary comparisons should therefore be read as exploratory summaries with uncertainty, not as substitutes for a prespecified participant-level analysis. The registry record lists no reported analyses. The actual missing-data approach, analysis populations, handling of incomplete sampling, and the sponsor’s inferential methods are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, including the primary Cmax endpoint and six named secondary outcomes, and reports no analyses in its analyses listing. It does not describe a statistical analysis plan, a hierarchy of hypotheses, or a method for controlling the chance of false-positive findings across multiple comparisons. The recalculated secondary p-values are unadjusted. They should not be read as confirmatory evidence without information about which comparisons were prespecified and how multiplicity was intended to be handled.

Missing-data methods are not reported in the registry record. The record gives sampling schedules and group sizes but does not state how missing blood samples, incomplete concentration profiles, unusable measurements, or participants who did not complete all periods were handled. It also does not describe whether analyses used an intention-to-treat population, a pharmacokinetic population, or another analysis set. The posted group counts differ by endpoint and treatment group, but the reasons for those counts are not reported in the registry record.

These gaps are consequential in a crossover study. In general, incomplete period data can affect which within-participant comparisons are available, while a participant-level model may need to account for treatment, period, and sequence. The registry record does not report whether those factors were included or how any carryover considerations were handled. This is not evidence that the analyses were inadequate; it means their methods cannot be evaluated from the record.

The record also does not report interim analyses or the study-specific sample-size justification. The posted sample-size scenarios are planning illustrations based on observed effects and stated assumptions, rather than evidence about the trial’s original design rationale. Without a prespecified analysis plan and complete methods, the secondary results are most appropriately treated as exploratory and the primary comparative result remains unreported.

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.

The registry reports zero serious adverse events and zero deaths in each posted group: 400 mg aramchol meglumine, 200 mg aramchol meglumine, and 300 mg aramchol free acid. It also reports zero other adverse events in each group. The numbers at risk are 16, 14, and 12, respectively. These figures are event counts for the groups as listed in the record.

Zero recorded events in these groups does not establish that an event cannot occur, nor does it show that the groups have identical safety profiles. The groups are small, and the record does not provide event-level descriptions or detailed exposure-adjusted safety analyses. Because the study is a crossover, the group entries should not automatically be interpreted as independent parallel treatment arms or as representing unique participants without overlap; the registry does not provide enough detail to determine that from these safety figures.

The serious adverse event counts are distinct from the pharmacokinetic findings. They do not establish clinical safety beyond the observations recorded for this study, and they do not support medical advice. The record’s posted figures are limited to the listed event counts and deaths.

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

The registry results describe pharmacokinetic measurements in a small Phase 1 study of healthy volunteers. The primary Cmax summaries differ across the posted dose and formulation groups, but the record does not report a primary comparative estimate or its uncertainty. The secondary results offer selected additional measures and recalculated unadjusted comparisons; they do not supply the missing primary analysis or a complete account of the registered outcomes.

These data can help describe concentrations observed after the studied doses and formulations. They do not establish what would happen in people with a health condition, under repeated dosing, or in clinical use. The record identifies healthy volunteers and a Phase 1 relative bioavailability study. It does not report clinical outcomes that would establish patient benefit. Concentration differences should not be translated into a claim that a treatment works or does not work.

The comparisons also involve different doses, and the registry’s period descriptions do not fully explain the posted group assignments. Therefore, the group summaries cannot be interpreted as an isolated formulation comparison at an identical dose. The crossover designation suggests a design intended to compare treatments across study periods, but the participant-level sequence and analytical handling are not reported in the registry record.

Uncertainty is central to interpreting these results. Group means and geometric means describe central values, while variability and confidence intervals help indicate precision. The primary endpoint lacks a posted contrast and confidence interval. For secondary outcomes, unadjusted calculations from summary statistics have limitations and should be considered exploratory. The record does not report multiplicity control, missing-data methods, analysis populations, or a full statistical analysis plan.

In short, the registry provides a limited descriptive pharmacokinetic record, not a definitive comparative conclusion. Absence of a reported analysis is not evidence that no analysis was conducted, but the record does not allow its methods or results to be assessed.

13. Why This Trial Matters Statistically

This trial illustrates why a registry result needs to be read in light of both design and reporting. A crossover design can be useful for pharmacokinetic comparisons because participants may contribute measurements across study periods. In general, that structure can reduce the impact of stable between-person differences. But appropriate interpretation depends on the actual treatment sequences, period effects, and the statistical model—details not reported in the registry record.

The study also shows the difference between descriptive endpoint summaries and an inferential treatment comparison. Cmax is identified as the primary endpoint, and group-level geometric means are posted. Without a comparative estimate and confidence interval, readers cannot evaluate the primary contrast’s precision from the registry results. A numerical difference between summaries is not by itself a complete statistical finding.

Another statistical issue is that the posted groups use different doses as well as different formulations. That makes it important to avoid attributing every contrast to formulation alone. The record’s secondary comparisons are unadjusted recalculations from summary statistics, while the analyses listing reports no analyses. They can provide exploratory context, but they cannot replace a reported participant-level analysis or account for every aspect of a crossover design.

Finally, sample-size planning illustrations based on observed effects are not observed power and do not explain the original trial design. Multiple secondary comparisons, incomplete reporting of missing-data methods, and unknown analysis populations all affect how strongly results can be interpreted. The statistical importance of this record lies partly in what it reports and partly in the methods needed for stronger conclusions that are not reported in the registry record.

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 trial-specific limitation is that the registry does not report an inferential analysis for the primary Cmax endpoint. It provides group summaries but no treatment contrast, confidence interval, or p-value. The posted results therefore do not quantify the uncertainty around the primary comparative question.

There are also dose differences across the listed groups: 400 mg and 200 mg aramchol meglumine are compared with 300 mg aramchol free acid. A contrast between these groups cannot isolate formulation from dose. Although the registry identifies a randomized crossover design and describes treatment assignment in later periods, it does not give a complete sequence description that links participants, periods, and the posted group sizes.

Three secondary outcomes have posted summaries and recalculated comparisons, while the registry lists six secondary outcomes. The reason the other listed outcomes lack posted results is not reported in the registry record. The available secondary comparisons are unadjusted calculations from summary statistics, rather than reported sponsor analyses. They do not show how within-participant dependence, treatment period, sequence, or carryover was addressed.

The record does not report a statistical analysis plan, multiplicity approach, missing-data method, analysis populations, interim analyses, or the study’s sample-size justification. Group counts differ across the posted outcomes, but reasons for those counts are not reported. The small group sizes also make estimates sensitive to individual observations, particularly when outcome variability is substantial. These limits do not negate the descriptive information, but they restrict how confidently it can support comparative conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparing The PK Of Aramchol Meglumine Granules To Aramchol Free Acid Tablets — NCT06502561.
• Registry record last updated 2026-06-01; status last verified 2026-03.
• Results first posted 2026-06-01.
• 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

NCT06502561 is a completed Phase 1 randomized, unmasked crossover study sponsored by Galmed Pharmaceuticals Ltd. It enrolled 16 healthy volunteers and compares pharmacokinetic measures for aramchol meglumine granules and aramchol free acid 300 mg tablets. The registry describes a single 400 mg aramchol meglumine dose for all participants in Period 1 and 1:1 randomization to aramchol meglumine or reference aramchol free acid in Period 2 and Period 3.

The primary endpoint is Cmax, reported as geometric means and geometric coefficients of variation. The registry posts group summaries but no primary comparative analysis. Selected secondary results include unadjusted recalculations from summary statistics. The registry record does not report the full statistical analysis plan, multiplicity handling, missing-data methods, or analysis populations. Serious adverse events, other adverse events, and deaths are listed as zero in each posted group.