A Pharmacokinetic Study of Padsevonil in Study Participants With Either Normal or Moderately Impaired Hepatic Function: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pharmacokinetic Study of Padsevonil in Study Participants With Either Normal or Moderately Impaired Hepatic Function (NCT04136444), a non-randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL).

2. Clinical Question

The study’s stated purpose was to evaluate padsevonil pharmacokinetics, safety and tolerability in participants with and without hepatic impairment. Its primary endpoint focuses on drug concentration in plasma rather than a clinical outcome. The contrast of interest is therefore pharmacokinetic: whether the posted concentration summaries differ across the hepatic-function groups. The record identifies the two categories of hepatic function but does not clearly map those categories to Cohort A and Cohort B, so the cohort labels in the safety data cannot be used to identify which category had each count.

The registry lists an enrollment of 12. That figure describes the study enrollment, not the number of participants contributing to every endpoint or every safety group. The primary endpoint population is a defined pharmacokinetic subset, and the record does not report the number included in that subset. Because the posted results do not include Cmax estimates, this page can explain the question and how the endpoint is summarized, but cannot state the observed magnitude or direction of a pharmacokinetic difference.

3. Trial Design

This was an open-label, nonrandomized, parallel-group phase 1 study sponsored by UCB Biopharma S.P.R.L. The registry lists healthy study participants and participants with impaired hepatic function as the conditions under study. The official title identifies the impaired-function category as moderate impairment, Child-Pugh Class B. Participants in both described groups were to receive assigned single and multiple doses of padsevonil.

The registry reports enrollment of 12, a study start date of 2019-10-28, and a primary completion date of 2020-05-22. The study status is terminated. The reason for termination is not reported in the registry record. The planned design is parallel rather than crossover, but the record does not specify the allocation process beyond identifying it as nonrandomized. It also does not provide the dose levels, sequence of dose administration, or details of how participants were assigned to cohorts.

Open-label means the record does not describe masking of treatment assignment. That is relevant to interpreting subjective outcomes, although the primary endpoint is a laboratory concentration measurement. Nonrandomized allocation also means the groups should not be treated as if they were randomized and exchangeable. Differences between groups could reflect characteristics other than hepatic function; the record does not describe adjustment for such differences.

The safety results are organized by Cohort A or Cohort B and by single-dose or multiple-dose study set. The registry does not define the cohort labels or establish whether participants appearing in the single-dose and multiple-dose entries are distinct. These entries should therefore be read as separate reported group summaries, not combined into a new overall count. The record reports 8 outcome measures and 0 analyses. It does not report a detailed statistical analysis plan or a sample-size justification.

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: Participant Flow refers to the Safety Set (SS).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Pharmacokinetic Set (PKS) is a subset of the Full Analysis Set (FAS), consisting of those study participants who had no important protocol deviations affecting the PK parameters and had a sufficient number of samples available to determine at least 1 PK parameter. All PK analyses were performed using the PKS.

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: Baseline Characteristics refer to the Safety Set (SS) which consisted of all study participants who received at least 1 dose of the investigational medicinal product (IMP).

6. Primary Endpoint

The registry lists the primary outcome as Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL), measured over Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

The primary endpoint is maximum plasma concentration, Cmax, after a single dose of padsevonil. Cmax is the highest observed concentration in the plasma samples collected for the endpoint. The registry specifies nanograms per milliliter (ng/mL) as the unit and identifies the summary measure as a geometric mean with a 95% confidence interval.

Plasma sampling was scheduled predose on Day 1 and at 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose. This schedule is intended to capture concentrations over time, including the observed peak. The registry’s description says Cmax is the maximum observed plasma concentration; it does not report the endpoint values or the number of participants contributing to them.

In general, Cmax is used in pharmacokinetic studies to describe the peak concentration reached after a dose. A geometric mean summarizes values on a multiplicative scale and can be useful when concentrations are positively skewed. A confidence interval conveys uncertainty around an estimated summary; it is not a range containing every participant’s concentration. These are general interpretations of the measures, not findings about this study. The posted results do not include a geometric mean or confidence interval, so the endpoint cannot be interpreted as showing a higher or lower peak concentration in either hepatic-function group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a geometric mean for maximum plasma concentration after a single dose, accompanied by a 95% confidence interval. It does not report a complete statistical analysis plan, the method used to calculate the interval, or a numerical endpoint estimate. The explanations below describe the statistical ideas in general and distinguish them from methods confirmed for this study.

What does Cmax measure?

Cmax is the maximum observed plasma concentration among the samples collected after dosing. It is a measured pharmacokinetic summary, rather than a clinical outcome such as a symptom or event. The sampling schedule in the registry runs from predose on Day 1 through 96 hours postdose, with scheduled measurements at 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours. In general, the observed maximum depends on the samples available and the timing of collection. The registry does not report individual concentration profiles or the resulting Cmax values.

Why use a geometric mean?

In general, concentration data can be asymmetric, with a small number of comparatively high values. A geometric mean summarizes measurements on a multiplicative scale and can be appropriate for data with that pattern. It is not the same as an arithmetic average, and its interpretation is most natural for positive values. The registry identifies the geometric mean as the summary measure but does not explain the rationale, state whether the data were log-transformed for analysis, or describe the calculation in further detail. Those specifics are not reported in the registry record.

What does the confidence interval communicate?

In general, a confidence interval describes the uncertainty around an estimated population quantity under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, but does not show the full spread of individual participant values. The registry specifies a 95% confidence interval for the Cmax geometric mean. It does not post the interval limits, the method used to construct the interval, or an estimate to which the interval applies. Consequently, neither the precision of the study’s Cmax estimate nor the compatibility of different values with the data can be assessed from the posted results.

How should a group comparison be understood?

The study has parallel groups defined by hepatic-function status, but allocation is nonrandomized. In general, a group comparison describes how the measured outcome differs between the groups; it is not automatically a causal estimate. Differences in participant characteristics or other factors may contribute to an observed contrast. The registry does not report a formal comparison, a model, covariate adjustment, or the exact contrast used for the primary endpoint. It also does not identify Cohort A and Cohort B as the normal-function and impaired-function groups in the safety entries. No group effect should therefore be inferred from the cohort labels or safety counts.

What can the planning illustrations tell us?

The page includes calculated sample-size illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning illustrations, not the study’s original design justification and not observed power. In general, a sample-size calculation describes the number of participants required under specified assumptions; it does not show what the study actually had power to detect after the fact. The registry record does not report the study’s own sample-size justification, and the primary result needed to interpret an illustration based on the observed effect is not posted.

What analyses are actually documented?

The registry lists 0 analyses. It identifies the primary outcome summary and defines the PKS, but does not provide a full statistical methods account. The phrase describing the PKS ends with a statement that all pharmacokinetic analyses were performed, without completing the description. Details such as transformations, handling of values below assay limits, model selection, covariate adjustment, and confidence-interval construction are not reported in the registry record. These omissions matter because statistical choices can affect both the estimate and its uncertainty. Without the numerical results and methods, the page can explain the intended summaries but cannot reproduce or validate the primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and identifies one primary endpoint: Cmax after a single dose of padsevonil. It also lists safety outcomes concerning treatment-emergent adverse events, serious adverse events, and treatment-emergent adverse events leading to discontinuation. However, the registry lists 0 analyses and does not report how multiple outcomes or comparisons were handled. Any multiplicity strategy, including whether adjustments were planned, is not reported in the registry record.

The primary endpoint analysis population is the PKS, a subset of the FAS. The PKS definition excludes participants with important protocol deviations affecting pharmacokinetic parameters and requires enough samples to determine at least one pharmacokinetic parameter. The registry does not define the FAS in the available description, provide the number of participants in either population, or say how many contributed to the Cmax analysis. The endpoint-specific missing-data rules and any imputation methods are not reported in the registry record.

The scheduled sampling times are described, but the record does not state how missed samples or incomplete concentration profiles were handled. It is also unclear whether any participants lacked an evaluable Cmax value. These gaps prevent assessment of whether the analyzed participants differed from those enrolled in ways that might affect the result. The study’s termination status does not explain whether outcome data were missing or why the study ended. The reason for termination and its implications for outcome availability are not reported in the registry 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 displays safety counts for Cohort A and Cohort B in both single-dose and multiple-dose entries. Serious adverse events are recorded as 0 among 3 at risk in each Cohort A entry, and as 0 among 9 at risk in each Cohort B entry. Deaths are recorded as 0 in all four entries. These are counts in the posted group summaries, not proof that an event could not occur.

The corresponding other-adverse-event counts recorded as affected are 3 in Cohort A Single Dose, 6 in Cohort B Single Dose, 3 in Cohort A Multiple Dose, and 7 in Cohort B Multiple Dose. The registry does not supply event-level detail for these entries in the displayed details. It lists treatment-emergent adverse events among the secondary outcomes, but the group summaries label these counts as other adverse events; the categories should not be treated as interchangeable without further definition.

The record does not define Cohort A and Cohort B in terms of hepatic function or clarify whether the same participants appear in single-dose and multiple-dose entries. Do not add the entries to create a total: the participant overlap is not reported in the registry record. The counts are descriptive and do not establish a comparative safety effect.

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

This trial addresses a pharmacokinetic question: how the maximum observed plasma concentration of padsevonil after a single dose is summarized in participants with normal versus moderately impaired hepatic function. Its phase 1, open-label, nonrandomized, parallel-group design is suited to describing drug concentration and safety measurements in the studied groups. The registry identifies a geometric mean and 95% confidence interval as the primary summary.

The posted record does not include the primary Cmax estimates, confidence interval limits, or a group comparison. It therefore does not show whether the observed concentration was higher, lower, or similar between the hepatic-function categories, nor how precisely any estimate was determined. The absence of a posted result is not evidence that the groups had identical results. It means that the primary outcome cannot be interpreted from the registry information.

The safety entries report zero serious adverse events and zero deaths in the listed groups, along with counts for other adverse events. These are limited descriptive counts. The registry does not provide event-level details or establish that the cohort entries represent independent sets of participants. The counts cannot be used to infer a causal safety difference between hepatic-function groups.

More generally, the registry record does not report the analysis plan, outcome-specific analysis counts, missing-data approach, or reason for termination. The enrollment of 12 does not establish how many participants contributed to the primary analysis. The planning illustrations are hypothetical calculations under stated assumptions, not observed power or evidence about the size of an actual treatment effect. The most defensible reading is therefore that the record documents a pharmacokinetic study and some safety summaries, while leaving the central numerical pharmacokinetic finding unavailable.

13. Why This Trial Matters Statistically

This study illustrates why pharmacokinetic endpoints and clinical outcomes answer different questions. Cmax describes a measured plasma concentration after dosing; it is not itself a measure of clinical benefit. For this study, the registry’s stated question concerns whether the concentration summary differs by hepatic-function category. A numerical estimate and its uncertainty would be needed to judge the size and precision of that contrast, but the posted record does not include them.

The design also matters. The study is nonrandomized, so hepatic-function groups are not described as randomly assigned. In general, this makes it important to understand how the groups compare and whether the analysis accounts for relevant differences. The record does not report group characteristics, a model, or adjustment methods. It also leaves Cohort A and Cohort B undefined in the safety listings, underscoring why labels should not be substituted for a clear description of the comparison.

Finally, the registry distinguishes a study’s planned or summarized outcomes from its actual inferential results. It reports the endpoint summary type and the PKS definition, but lists 0 analyses and no Cmax values. The planning illustrations on the page can demonstrate how sample-size assumptions relate to a target effect in general; they cannot recover unposted results or establish observed power. For statistical interpretation, the missing estimates and methods are as important as the design details that are present.

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 consequential limitation for interpreting this trial is that the registry does not post the primary Cmax estimate or its 95% confidence interval. Without those values, the direction, magnitude, and precision of the pharmacokinetic result are unknown. The registry also lists 0 analyses, so no inferential result or formal group comparison is available to review.

Enrollment was 12, but the number included in the PKS or in the Cmax analysis is not reported in the registry record. The PKS definition indicates that eligibility for pharmacokinetic analysis depended on protocol deviations and sample availability, which means the analysis population may differ from total enrollment. The record does not report how many participants were excluded from the PKS or why.

The design is nonrandomized and open-label. The registry does not provide group baseline characteristics, the assignment process, or adjustment methods. It also does not explain which hepatic-function category corresponds to Cohort A or Cohort B. Safety entries are split by cohort and single-dose or multiple-dose study set, but whether participants overlap across entries is not reported. The reason the study was terminated is also not reported in the registry record.

Finally, the registry does not provide dose levels, the detailed analysis plan, missing-sample handling, or the method used to construct the confidence interval. These gaps restrict assessment of both the primary endpoint and the safety summaries. They do not justify filling in the missing results or assuming that the listed design details resolve the uncertainty.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Pharmacokinetic Study of Padsevonil in Study Participants With Either Normal or Moderately Impaired Hepatic Function — NCT04136444.
• Registry record last updated 2021-07-28; status last verified 2021-07.
• Results first posted 2021-07-28.
• 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 is a phase 1, open-label, nonrandomized, parallel-group study of padsevonil in participants with normal or moderately impaired hepatic function. The registry lists enrollment of 12 and identifies maximum plasma concentration after a single dose as the primary endpoint, summarized by a geometric mean with a 95% confidence interval. It describes a pharmacokinetic analysis population but does not report the number analyzed.

The study is marked terminated, and the reason is not reported in the registry record. The record lists 8 outcome measures and 0 analyses. It includes selected safety counts, but does not post the primary Cmax estimates, confidence interval limits, or a formal comparison between hepatic-function groups. Consequently, the central pharmacokinetic finding and its precision cannot be determined from the posted results.