A Study of Soticlestat in Adults With Liver Failure Compared to Those With Normal Liver Function: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Soticlestat in Adults With Liver Failure Compared to Those With Normal Liver Function (NCT05098054), a non-randomized phase 1 study. The primary outcome is Cmax: Maximum Observed Plasma Concentration for Soticlestat.

2. Clinical Question

The study title and official title frame the investigation as a Phase 1 pharmacokinetics and safety study. Its focus is the relationship between hepatic-function status and drug exposure after one dose, rather than a comparison of treatment strategies over time. The registry record lists moderate and mild hepatic impairment alongside normal hepatic function as the principal groups for this question.

The planned reference group can help describe observed concentration patterns in participants with normal hepatic function relative to those with impairment. Because assignment was non-randomized, however, group differences could reflect differences between participants as well as differences in hepatic function. The registry record does not describe a randomized allocation process or a matched comparison strategy.

3. Trial Design

This was a completed Phase 1, non-randomized, unmasked, parallel-group study of oral soticlestat. The registry record lists enrollment of 36 participants. Its official title describes participants with moderate or mild hepatic impairment and normal hepatic function. The intervention descriptions specify three arms: moderate impairment, mild impairment, and normal hepatic function, each receiving soticlestat 300 mg once on Day 1.

Participants were to stay at the study clinic for 8 days, receive a single dose, and be monitored. Follow-up was planned about a week after clinic discharge. The primary pharmacokinetic measurement was taken before dosing on Day 1 and at multiple post-dose time points up to 144 hours. This schedule is intended to characterize concentration over time after administration, including the observed peak concentration.

The study started on 2021-10-29, reached primary completion on 2022-05-31, and is listed as completed. Takeda is identified as the sponsor. The registry record lists hepatic impairment and healthy volunteers among the conditions.

Non-randomized allocation means participants were not assigned to hepatic-function groups by chance as part of the described design. The parallel model means the groups were followed as separate groups rather than participants crossing between conditions. The absence of masking is also recorded. Details of any matching, stratification, or adjustment for differences between groups are not reported in the registry record.

The adverse-event record includes a group titled severe hepatic impairment, with one participant at risk. That group does not appear among the three arm descriptions. The registry record does not explain the relationship between that safety group and the described arms, so it should not be assumed to represent an additional planned arm without further documentation.

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: Participants diagnosed with moderate/mild hepatic impairment (HI) compared to matched healthy participants with normal hepatic function received single dose of soticlestat. 1 with severe HI, 8 with moderate HI, 8 with mild HI and overall 19 participants with normal hepatic function (12 matched to moderate HI and 12 matched to mild HI participants) were enrolled. Five of same participants with normal hepatic function served as matched to moderate and mild HI.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) Analysis Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (example, exposure to treatment, availability of measurements and absence of major protocol violations) and were included in the statistical analyses. Five of the same participants with normal hepatic function served as matched to moderate and mild HI arms.

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: Safety analysis set included all participants who received the dose of soticlestat.

6. Primary Endpoint

The registry lists the primary outcome as Cmax: Maximum Observed Plasma Concentration for Soticlestat, measured over Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose.

The primary endpoint is Cmax, the maximum observed plasma concentration of soticlestat, measured in nanograms per milliliter. It captures the highest concentration recorded in the scheduled blood samples after dosing. The registry lists the measurement window as Day 1 before dosing and multiple time points up to 144 hours after dosing.

Cmax is used in pharmacokinetic research because it describes peak observed exposure. Comparing this measure across groups can help characterize whether concentration profiles differ with hepatic-function status. It is not, by itself, a measure of symptom change, disease control, or clinical benefit. A concentration difference would describe drug exposure under the study conditions; interpretation of its clinical importance would require additional evidence.

The planned summary measure is the geometric mean, with geometric coefficient of variation as the measure of dispersion. In general, a geometric mean is appropriate for positive measurements that are right-skewed or vary multiplicatively: values are analyzed on a logarithmic scale and then expressed back on the original scale. The geometric coefficient of variation conveys relative variability around that geometric mean. It should not be read as a confidence interval or as the range containing individual participants' measurements.

The registry record does not report group-specific Cmax values, the corresponding geometric coefficients of variation, confidence intervals, or a statistical test for the primary endpoint. Consequently, the endpoint definition is available, but the observed pharmacokinetic contrast and its precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The central statistical task in this study is to describe a pharmacokinetic measure across groups defined by hepatic-function status. The primary endpoint, Cmax, is a positive concentration measurement. The registry specifies a geometric mean and geometric coefficient of variation rather than an arithmetic mean and standard deviation. In general, this choice is useful when measurements are skewed or when proportional variation is more meaningful than variation by a fixed absolute amount.

What does a geometric mean describe?

In general, a geometric mean is calculated by transforming positive values to a logarithmic scale, averaging those transformed values, and converting the average back to the original scale. This approach gives a summary that is less dominated by a few large observations than an arithmetic mean can be when data are right-skewed. It also fits settings where multiplicative differences are relevant. The registry identifies this summary measure, but the group-level estimates are not reported in the registry record.

The geometric coefficient of variation describes relative dispersion around a geometric mean. In general, it is useful for comparing variability when the scale of the measurement changes across groups. It is not a confidence interval, and it does not directly show the spread of all individual observations. Readers need the estimate, the dispersion measure, and preferably a measure of uncertainty to judge how precisely a group result is known. The registry record does not report those primary endpoint values.

Why measure the peak concentration?

Cmax is the largest concentration observed among the scheduled samples. Here, blood sampling was planned before dosing on Day 1 and at multiple times after dosing, up to 144 hours. In general, the measured peak depends on the sampling schedule: a peak between scheduled samples may not be captured exactly. The endpoint is therefore the maximum observed value, not necessarily a direct measurement of the precise moment of a biological peak.

Concentration-time sampling also supports characterization of exposure over time, but the primary endpoint named in the record is Cmax. The registry lists four outcome measures and six analyses, without providing a complete account of their estimates or methods. The other outcome definitions and results are not reported in the registry record.

How should group comparisons be understood?

The study uses a parallel-group design and non-randomized allocation. In general, parallel groups permit comparison of measurements between separate participant groups. When the groups are defined by a health characteristic rather than assigned at random, they can differ in other ways as well. A difference in an outcome may therefore be associated with group status without proving that the status alone caused it.

Randomization is often used in trials to balance measured and unmeasured participant characteristics across assigned treatment groups, on average. That protection does not apply in the same way when allocation is non-randomized. The registry record does not report a method for matching groups, controlling confounding, or adjusting the primary comparison. It also does not report a formal primary comparison or its uncertainty. Accordingly, even if group estimates were available, interpretation would need to respect the observational nature of group assignment.

What does over-dispersion mean in general?

In general, over-dispersion occurs when observations vary more than a statistical model expects. If a method assumes less variability than the data contain, standard errors and confidence intervals may be too small, making results appear more precise than they are. For concentration measurements, variability can arise from differences between participants and from measurement or sampling features. The geometric coefficient of variation offers a descriptive view of relative variability, but the record does not report values that would permit an assessment of dispersion or model fit.

What can a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate under a particular statistical procedure. It helps distinguish a precisely estimated quantity from one that remains compatible with a broad range of values. It does not guarantee that the true value lies within a particular interval, and its interpretation depends on the design and method. No confidence interval for the primary Cmax endpoint is reported in the registry record, so its precision cannot be evaluated from the posted results.

How should planning illustrations be read?

The stated planning assumptions describe illustrations based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is framed as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed using those exact values. The registry record does not report the trial's own sample-size justification.

In general, a sample-size illustration asks how many participants per arm might be needed under stated assumptions to detect a specified effect with a chosen power. Such an illustration depends on the effect size and variability used as inputs. The record does not report an observed primary effect or numerical planning estimates in the listed details, so no particular required sample size can be interpreted. Planning figures are not observed power and do not describe the probability that the study's result is true.

The statistical analysis plan, including the tests used for the primary comparison, handling of missing concentrations, and any model assumptions beyond the listed planning assumptions, is not reported in the registry record. It would be inappropriate to infer these details from the endpoint summary measure alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures and six analyses. It does not identify all outcome definitions and analysis details in the available record, state which results were designated primary for each analysis, or report how multiple comparisons were addressed. When several outcomes, groups, or analyses are examined, the chance of at least one apparently notable result can increase. In general, prespecified testing hierarchies or multiplicity adjustments can help control this issue, but no such approach is reported in the registry record.

Missing-data handling for the primary pharmacokinetic endpoint is also not reported in the registry record. The outcome's population description refers to a Pharmacokinetic Analysis Set, including participants who complied sufficiently with the protocol and had an evaluable pharmacokinetic profile, with examples involving treatment exposure, measurement availability, and major protocol violations. That description is incomplete in the registry record, ending with the words “Five of”. The record does not establish how many participants were included in the analysis, how many were excluded, or how unevaluable measurements were handled.

In general, excluding participants without evaluable profiles can affect the interpretation if the reasons for missing or unusable measurements are related to participant characteristics or outcomes. A complete account would describe the analysis population, exclusions, missingness, and any sensitivity analyses. Those details are not reported in the registry record. It is therefore not possible to assess whether the primary analysis represents all enrolled participants or only a subset, or how robust it is to missing-data assumptions.

The registry also does not report whether interim analyses were planned or conducted, or provide a full statistical analysis plan. These omissions do not establish that a particular method was or was not used; they limit what can be concluded from the public record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events, other adverse events, and deaths by listed group. No serious adverse events were recorded in the severe hepatic impairment group, moderate hepatic impairment group, mild hepatic impairment group, or normal hepatic function group. No deaths were recorded in any of those groups.

For other, non-serious adverse events, the record reports 1 participant affected among 1 at risk in the severe hepatic impairment group, 1 among 8 in the moderate impairment group, 1 among 8 in the mild impairment group, and 2 among 19 in the normal hepatic function group. These are participant counts, not event rates calculated. The registry's secondary outcome is the number of participants reporting one or more treatment-emergent adverse events.

These observations are descriptive and should be read in the context of the study's group sizes and follow-up. A count of zero serious events means none were recorded in the listed group during the study reporting period; it does not demonstrate that such events cannot occur. Small groups provide limited information about uncommon events. The record does not report the non-serious event terms, severity details, or event-level timing, so the nature and clinical context of those reports cannot be characterized from these counts alone.

The severe impairment safety group is listed despite not appearing in the described study arms. The registry record does not explain that discrepancy. Its safety count should be reported as a registry group, without assuming how it relates to the three described arms.

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

This study addresses a focused pharmacokinetic question: the observed maximum plasma concentration of soticlestat after one oral dose in participants with different hepatic-function status. The registry describes the planned dose, groups, monitoring, sampling window, and summary measure. It also posts selected adverse-event counts. These details define the question and provide limited descriptive safety information.

The primary Cmax results themselves are not reported in the registry record. Without group estimates and an uncertainty measure, readers cannot determine the observed magnitude or direction of any concentration difference, or how precise such a difference would be. The completed status of the study does not substitute for the missing numerical findings.

Even with numerical group results, a non-randomized comparison would not establish that hepatic-function status alone caused a difference. Groups may differ in other characteristics, and adjustment or matching methods are not reported in the registry record. The results would characterize the participants studied under the stated conditions rather than prove a causal effect of hepatic impairment.

The safety counts indicate that no serious adverse events or deaths were recorded in the listed groups, while non-serious events were recorded. They are not enough to establish comparative safety or to rule out uncommon events. The record does not include the event terms needed to describe the non-serious reports in more detail.

These results, as posted, also do not answer questions about repeated dosing, longer-term outcomes, effectiveness, or populations outside those described. The study used a single dose of soticlestat 300 mg and had a specified clinic stay and follow-up period. The registry record does not report evidence that would support broader conclusions about treatment effects. Its contribution in the available record is the design description and selected safety counts, not a complete presentation of the primary pharmacokinetic findings.

13. Why This Trial Matters Statistically

Pharmacokinetic studies can clarify how drug concentrations are characterized in groups with different organ-function status. A peak concentration such as Cmax is one part of that assessment: it describes the highest measured concentration after dosing. In this study, the planned comparison is between participants with moderate or mild hepatic impairment and participants with normal hepatic function after a single oral dose.

Statistically, the design makes the distinction between a reference group and a randomized control group important. Participants were grouped by hepatic-function status rather than randomly assigned to those statuses. That allows descriptive comparison but leaves open the possibility that other differences between participants contribute to any observed contrast. Clear reporting of estimates, uncertainty, analysis populations, and adjustment methods would help readers judge the strength and limitations of the evidence.

The record's endpoint definition is useful, but the absence of numerical primary results limits its statistical contribution. A geometric mean and geometric coefficient of variation indicate how the endpoint was intended to be summarized; without their values, readers cannot assess the observed concentration pattern or its variability. The same principle applies to confidence intervals and analysis details: methods and estimates are both needed for a meaningful interpretation.

The posted safety counts also illustrate why denominators and group definitions matter. Counts can be understood only in relation to the participants at risk, and the severe impairment safety group is not among the three described study arms. Explicitly reconciling such group labels would improve clarity. Overall, the record outlines a relevant Phase 1 pharmacokinetic question, but the missing primary estimates and incomplete methodological details constrain what can be learned statistically from the posted results.

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 principal limitation of the available record is that it does not report numerical results for the primary Cmax endpoint. Group estimates, dispersion values, confidence intervals, and a formal comparison are not reported in the registry record. This prevents assessment of the size, direction, and precision of the primary pharmacokinetic findings.

Allocation was non-randomized, so any comparison across hepatic-function groups is subject to potential confounding. The registry record does not report matching, adjustment, or other methods for addressing baseline differences. It also does not provide participant characteristics that would allow readers to assess group comparability.

The description of the Pharmacokinetic Analysis Set is incomplete, ending with “Five of”. The number included in the primary analysis, exclusions from that population, and handling of missing or unevaluable measurements are not reported in the registry record. The record also does not give a complete statistical analysis plan, specify multiplicity handling, or describe interim analyses.

The adverse-event record includes a severe hepatic impairment group with one participant at risk, although the described study arms cover moderate impairment, mild impairment, and normal hepatic function. The relationship between that safety group and the described arms is not reported in the registry record. Non-serious adverse-event terms and further clinical details are also not reported.

The study evaluated a single dose and a limited follow-up period as described in the registry. The available information does not establish how findings would apply to repeated administration or other settings. In addition, the registry does not report the trial's sample-size justification, and the stated planning assumptions do not provide the missing primary estimates.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Soticlestat in Adults With Liver Failure Compared to Those With Normal Liver Function — NCT05098054.
• Registry record last updated 2026-09-15; status last verified 2026-08.
• Results first posted 2024-02-02.
• 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

This completed Phase 1, non-randomized, unmasked, parallel-group study examined a single oral dose of soticlestat 300 mg in participants with moderate or mild hepatic impairment and healthy participants with normal hepatic function. Enrollment was 36. The primary endpoint was maximum observed plasma concentration, summarized using a geometric mean and geometric coefficient of variation, with sampling planned from pre-dose through 144 hours after dosing.

The registry lists four outcome measures and six analyses. It reports no serious adverse events or deaths in the listed safety groups and reports non-serious adverse events in some participants. A severe hepatic impairment safety group is included in the adverse-event record, though it is not among the described arms.

Group-level primary pharmacokinetic results, confidence intervals, full analysis details, missing-data methods, and multiplicity handling are not reported in the registry record. The study started on 2021-10-29, reached primary completion on 2022-05-31, and is listed as completed.