An Open-Label Study Following Oral Dosing of Seladelpar to Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment (HI): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-Label Study Following Oral Dosing of Seladelpar to Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment (HI) (NCT04950764), a non-randomized phase 1 study. The primary outcome is Part A: Pharmacokinetic (PK) Parameter: Cmax of Seladelpar and Its Metabolites (M1, M2, and M3).

2. Clinical Question

The study was designed around pharmacokinetics: the movement and concentration of a drug and its metabolites in the body over time. It was not a randomized comparison of clinical benefit. The registry lists pharmacokinetic measures, rather than a clinical outcome, as the primary endpoint. It also lists urine measures and relationships between plasma exposure and baseline albumin or bilirubin among secondary outcomes. Those measures can help characterize exposure and its association with participant characteristics, but the registry record does not provide their numerical results.

3. Trial Design

This was a Phase 1, open-label, non-randomized, sequential study sponsored by Gilead Sciences. The registry lists enrollment of 24 and a completed status. The recorded study start was 2021-11-16, and primary completion was 2025-02-24. Participants and study personnel were not masked, and treatment allocation was not randomized.

Part A had four cohorts. Participants in each cohort received a single oral 10 mg dose on Day 1. Cohorts were defined as CP-A without portal hypertension, CP-A with portal hypertension, CP-B, and CP-C. Child-Pugh classifications were listed as CP-A (score 5 to 6), CP-B (score 7 to 9), and CP-C (score 10 to 12). The CP-A cohorts were distinguished by whether portal hypertension was present.

Part B included participants in the CP-A with portal hypertension and CP-B cohorts who completed Part A. They received seladelpar 5 mg or 10 mg orally once daily for 28 days. The Part B dose was chosen for each participant based on exposure after the single dose in Part A. The record does not describe Part B as randomized, and dose selection was not an independent random assignment.

The sequential structure means the Part B groups were drawn from participants who had completed Part A, rather than from a separate randomized comparison. The registry does not report a separate control intervention. Although cohort descriptions specify the planned dosing, the record does not provide participant-level treatment histories or numerical pharmacokinetic findings. Consequently, the design can be described, but a comparative treatment effect cannot be established from the design description alone.

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: 37 participants were screened.

Only the first 6 of 8 groups are shown.

Part A

Part B

Analysis population for the primary outcome, as defined in the registry: The PK Analysis Set included all study participants who underwent PK sampling and for whom the PK profile could be adequately characterized based on available and analyzed samples.

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: The Safety Analysis Set included all study participants who received any amount of seladelpar.

6. Primary Endpoint

The registry lists the primary outcome as Part A: Pharmacokinetic (PK) Parameter: Cmax of Seladelpar and Its Metabolites (M1, M2, and M3), measured over Day 1: Predose; 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 hours postdose.

The primary endpoint was Cmax, defined in the registry as the maximum observed plasma concentration of the study drug. It covered seladelpar and its metabolites M1, M2, and M3, with measurements expressed in nanograms per milliliter. Sampling was scheduled from predose through 72 hours postdose on Day 1, with multiple collection times during that interval.

In general, Cmax is used in pharmacokinetic studies to describe the highest measured drug concentration following a dose. It complements measures based on concentration over time: a peak value describes the observed maximum, while an exposure measure based on the full concentration-time profile captures a different feature of drug disposition. Cmax may therefore help characterize whether peak plasma concentrations differ across groups with different hepatic impairment classifications. It does not, on its own, establish clinical benefit or harm.

The registry specifies that the endpoint was to be summarized as a mean with a standard deviation. The PK Analysis Set included participants who underwent pharmacokinetic sampling and whose PK profile could be adequately characterized from available and analyzed samples. However, the registry record does not report the actual Cmax means, standard deviations, or cohort-level estimates. It therefore does not permit interpretation of the size or precision of any observed differences in this primary measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a continuous pharmacokinetic measure summarized by a mean and standard deviation. The endpoint is Cmax for seladelpar and metabolites M1, M2, and M3. The registry does not report numerical endpoint summaries or a statistical analysis plan. The concepts below are general explanations of how such measurements and design features are commonly interpreted; they do not describe unreported procedures used in this trial.

What does Cmax describe?

In general, Cmax is the highest observed concentration in a participant’s measured concentration-time profile after a dose. It is a peak measure, not a complete description of exposure. The timing and density of blood sampling can affect the observed maximum: if a true peak occurs between sample times, the recorded maximum may not equal the unobserved peak. The registry lists sampling on Day 1 from predose through 72 hours postdose. It does not give actual concentration profiles or individual Cmax values.

The study also listed pharmacokinetic measures involving urine and plasma exposure. In general, different pharmacokinetic parameters summarize distinct features of drug disposition; a peak concentration and an exposure measure over time should not be treated as interchangeable. The registry names urine Ae0-t and CLR measures, as well as plasma exposure relationships with baseline albumin and bilirubin. It does not report their numerical estimates in the material described by the record.

Why report a mean and standard deviation?

In general, a mean gives a measure of the central value of a continuous outcome, while the standard deviation describes how dispersed participant measurements are around that mean. The standard deviation is not the same as the uncertainty in the estimated mean. A confidence interval, when reported, describes a range of values compatible with the data under the analysis assumptions and conveys precision in a way that depends on the number of observations and their variability. The registry names a mean and standard deviation for the primary endpoint, but does not report those values or confidence intervals.

Pharmacokinetic data can vary substantially between participants. In general, distributional shape matters when deciding how to summarize concentrations and exposure. Some analyses may use transformed values or geometric summaries when data are skewed, but the registry record does not report whether any transformation or alternative summary was used. It would be inappropriate to assume an analysis approach that is not stated.

What does the non-randomized structure imply?

Random allocation, in general, helps balance measured and unmeasured characteristics between groups in expectation. This study was not randomized. Its cohorts were defined by impairment classification and portal hypertension, and Part B dose choice depended on exposure observed after Part A. As a result, group differences cannot be attributed solely to dose or impairment status using a randomized comparison framework. Cohort summaries can describe the participants and measurements in each group, but they do not by themselves isolate causal effects.

The study was open-label, so masking was not used. For an objective laboratory concentration measurement, lack of masking may be less directly influential than it is for a subjective outcome, but it does not remove other sources of bias or uncertainty. Sample collection, handling, analysis, and participant selection still matter. The registry does not report details about these procedures beyond the scheduled sampling and the PK Analysis Set definition.

How should planning illustrations be understood?

In general, a sample-size planning illustration asks how many participants might be needed under specified assumptions to detect a chosen effect with a chosen statistical procedure. The registry-related description characterizes its illustrations as based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed or powered that way. The record does not report the trial’s own sample-size justification. An illustration based on an observed effect is not observed power and does not change the study’s actual design.

The illustrations also presume an equal-allocation comparison between two arms, while this study has non-randomized cohorts and exposure-based dose selection in Part B. Any such planning estimate must therefore be kept separate from the trial’s actual enrollment and design. No numerical planning estimates are described in the registry record.

What is not established by the record?

The registry lists 44 outcome measures and 36 analyses, but does not provide numerical results for the primary pharmacokinetic endpoint in this record. It also does not report inferential methods, confidence intervals, model specifications, handling of multiplicity, or missing-data procedures. These omissions limit assessment of the statistical evidence and mean that no claim about statistical significance or the precision of a group difference can be made from the endpoint description alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 44 outcome measures and 36 analyses. The primary endpoint is Cmax for seladelpar and its metabolites. Secondary outcomes include urine pharmacokinetic measures and relationships between plasma Cmax or exposure measures and baseline albumin or bilirubin. With multiple outcomes and analyses, there can be more than one opportunity to observe an apparently notable result. In general, multiplicity procedures may control the chance of false-positive findings across a defined family of tests, but the registry record does not report whether any such procedure was planned or used.

Numerical primary results, confidence intervals, and p-values are not reported in the registry record. The record also does not provide enough information to assess which outcomes were analyzed, whether the listed outcomes were prespecified in the same way, or how any analyses were prioritized. Statistical significance and the degree of precision therefore cannot be evaluated from the endpoint description.

The PK Analysis Set is defined as participants who underwent PK sampling and whose profiles could be adequately characterized from available and analyzed samples. That definition identifies an analysis population, but the record does not report how many participants were included in each endpoint analysis, the reasons profiles may have been inadequate, or how missing observations were handled. In general, missing pharmacokinetic samples can affect the ability to characterize a concentration-time profile and may affect which participants contribute to an analysis. The record does not state whether missingness was addressed through imputation, exclusion, or another method.

The registry does not report the statistical analysis plan, including any model adjustments, transformation of outcomes, multiplicity strategy, or sensitivity analyses. Those details are not reported in the registry record. Without them and without the numerical outcome results, it is not possible to reconstruct the inferential analysis or judge how robust findings may be to analysis choices.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: generalised oedema (20.0%), bronchitis (20.0%).

The registry reports serious adverse events, other adverse events, and deaths by cohort. In Part A, each of the four cohorts had 6 participants at risk for the listed safety summaries. No serious adverse events or deaths were reported in these Part A cohorts. Other adverse events were reported for 2 participants in the CP-A with portal hypertension cohort and 1 participant in the CP-B cohort; none were reported in the CP-A without portal hypertension or CP-C cohorts.

In Part B, the CP-A with portal hypertension 5 mg cohort and the CP-B 5 mg cohort each had 1 participant at risk, with no serious adverse events, other adverse events, or deaths reported. In the CP-A with portal hypertension 10 mg cohort, 1 participant had a serious adverse event and 2 had other adverse events among 5 at risk. In the CP-B 10 mg cohort, no serious adverse events were reported, 3 participants had other adverse events among 5 at risk, and no deaths were reported. No deaths were reported in any listed cohort.

The registry lists generalised oedema and bronchitis as serious adverse event terms at 20.0% each. The denominator and the basis for these term-level percentages are not reported in the registry record. Counts in small, non-randomized cohorts are descriptive; they do not establish comparative risk between doses or impairment groups. The registry does not provide event-level timing, duration, or attribution in the information.

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

This study addresses pharmacokinetics in a population with primary biliary cholangitis and hepatic impairment. Its primary measure, Cmax, is intended to describe peak plasma concentration after dosing. The registry also lists related pharmacokinetic outcomes involving metabolites, urine measures, and relationships with baseline albumin and bilirubin. This focus is different from testing a clinical benefit outcome in a randomized trial.

The registry record gives the cohort definitions, dosing schedule, endpoint definition, and safety counts, but does not report numerical results for the primary pharmacokinetic endpoint. It therefore does not show the size or precision of the observed concentrations, nor whether the measurements differed among the impairment cohorts. It also does not report numerical findings for the listed secondary outcomes. Claims about the direction or magnitude of exposure differences would go beyond the registry record.

The design does not support a like-for-like randomized treatment comparison. Part A cohorts reflect different hepatic impairment categories and portal hypertension status. Part B included selected participants who completed Part A, and their dose was chosen based on exposure after the earlier single dose. Consequently, observed differences between cohorts, even if numerical estimates were available, would not by themselves establish that dose or impairment caused the differences.

The safety counts show reported events in the listed cohorts, including one serious adverse event in the Part B CP-A with portal hypertension 10 mg cohort and none reported in the other listed cohorts. Such counts are descriptive, particularly in cohorts with few participants at risk. They are not a randomized safety comparison and do not establish how frequently events would occur in a broader population.

In general, pharmacokinetic findings can inform understanding of drug exposure, but they do not by themselves establish clinical outcomes. Here, the registry record does not include the numerical primary pharmacokinetic findings needed to assess exposure across cohorts. The record supports a description of what was studied and how it was structured, not a conclusion about treatment effects or clinical benefit.

13. Why This Trial Matters Statistically

Hepatic impairment can be an important context for studying drug exposure because pharmacokinetic measurements describe concentrations in the body, and the study specifically organized cohorts by Child-Pugh classification and portal hypertension status. A focused pharmacokinetic study can therefore ask a different question from a conventional efficacy trial: how exposure measures are characterized across groups with different clinical classifications.

Statistically, the design illustrates why the structure of a study matters when interpreting group summaries. The Part A cohorts were not randomized, and Part B dosing was selected using prior exposure. These features make descriptive cohort results distinct from a randomized estimate of a treatment effect. A numerical contrast does not become causal merely because it is expressed as a difference between groups.

The endpoint also illustrates why a study may report multiple pharmacokinetic dimensions. Cmax captures a peak concentration, while the listed secondary outcomes include urine measurements and plasma exposure measures. In general, each parameter answers a related but distinct question. Reading one measure as a complete description of drug exposure would overlook those distinctions.

The registry lists multiple outcomes and analyses, making clear reporting of analysis choices relevant to interpretation. The record does not report a multiplicity strategy, missing-data procedures, or numerical primary outcome results. That limits the extent to which readers can assess the precision and inferential strength of the study from the registry record.

Finally, the safety summaries emphasize the value of reporting counts by cohort while also showing the limits of descriptive data from small groups. Such counts communicate what was recorded in these cohorts, but without a randomized comparator they do not establish comparative risks. The study is statistically informative as an example of a sequential, non-randomized pharmacokinetic design, while its available record leaves the central quantitative exposure findings unreported.

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 question is that numerical Cmax results are not reported in the registry record. Without the cohort estimates and measures of variability, readers cannot assess the magnitude or precision of exposure patterns for seladelpar or its metabolites. Numerical results for the listed secondary pharmacokinetic outcomes are also not reported in the record.

The study was open-label and non-randomized. Cohort membership was determined by hepatic impairment classification and portal hypertension status, rather than random assignment. Part B included participants who completed Part A, and dose selection depended on their exposure after the single Part A dose. These features limit causal comparisons between cohorts and doses.

The registry lists enrollment of 24, but does not report how many participants contributed to each pharmacokinetic analysis. The PK Analysis Set requires sampling and an adequately characterized profile, so the analysis population may not be fully described by the enrollment figure alone. Reasons for exclusion from analyses and procedures for handling missing samples are not reported in the registry record.

The registry does not report the sample-size justification, statistical analysis plan, multiplicity approach, model details, or sensitivity analyses. It also does not provide confidence intervals or p-values for the primary endpoint. These omissions prevent a full assessment of the planned inference, precision, and robustness of the results.

Safety information is reported as cohort-level counts, but the registry does not provide event-level detail or the denominator and basis for the listed serious-event term percentages. With non-randomized cohorts, those figures should not be interpreted as comparative risk estimates. The available record supports a design and reporting description, but not a complete evaluation of pharmacokinetic or comparative safety findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Open-Label Study Following Oral Dosing of Seladelpar to Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment (HI) — NCT04950764.
• Registry record last updated 2026-05-04; status last verified 2026-04.
• Results first posted 2026-05-04.
• 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

NCT04950764 is a completed Phase 1, open-label, non-randomized, sequential study sponsored by Gilead Sciences. It enrolled 24 participants with primary biliary cholangitis and hepatic impairment. Part A evaluated a single oral 10 mg dose of seladelpar across four cohorts defined by Child-Pugh classification and portal hypertension status. Part B included selected CP-A with portal hypertension and CP-B participants who completed Part A, with daily 5 mg or 10 mg dosing for 28 days based on exposure after the Part A dose.

The primary endpoint was Cmax of seladelpar and metabolites M1, M2, and M3. The registry record does not report numerical primary endpoint results. Safety counts are reported by cohort, including one serious adverse event in the Part B CP-A with portal hypertension 10 mg cohort and no reported deaths. Because the study was non-randomized and the primary pharmacokinetic estimates are not reported, the registry record does not establish comparative treatment effects.