A Study to Test the Safety, and Tolerability of Padsevonil in Healthy Male Japanese Study Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Test the Safety, and Tolerability of Padsevonil in Healthy Male Japanese Study Participants (NCT04075409), a non-randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil.

2. Clinical Question

The study asks how padsevonil’s pharmacokinetic profile, safety, and tolerability are characterized in healthy male Japanese participants grouped by CYP2C19 genotype. Its primary endpoint focuses on the maximum plasma concentration after a single dose. The record also describes single-dose and multiple-dose treatment groups for extensive, intermediate, and poor metabolizers. The central pharmacokinetic question is whether measured padsevonil exposure, represented by peak plasma concentration, varies across these genotype groups. The registry record does not report numerical endpoint estimates or a formal between-group comparison, so it does not establish the size or precision of any genotype-related difference.

3. Trial Design

This is a Phase 1, open-label, non-randomized, parallel-group, single-center study. The registry record names UCB Biopharma S.P.R.L. as the sponsor and lists healthy Japanese participants as the condition. It reports an enrollment of 39. The study began on 2019-09-30, reached primary completion on 2019-12-27, and has a completed status.

Participants were categorized as extensive, intermediate, or poor metabolizers according to CYP2C19 genotype. Each group description says participants received assigned single and multiple doses of padsevonil. The record does not describe a placebo or an active comparator. Because allocation was non-randomized, the metabolizer groups should not be treated as randomized treatment arms or as a like-for-like controlled comparison. Genotype defines the groups; it is not an assigned intervention.

Open-label means the study was not masked. The registry record does not report further details about who knew the treatment assignment or whether any measurements were assessed independently. Parallel-group design means the record describes separate metabolizer groups rather than a crossover comparison. The protocol’s precise dosing schedule, eligibility criteria beyond the stated population, and recruitment procedures are not reported in the registry record.

The listed primary endpoint concerns a single dose, although the study also included multiple-dose groups. Those multiple-dose groups should not be confused with the primary endpoint’s single-dose measurement. The record does not explain the relationship between the single-dose and multiple-dose phases or state how dose levels were selected. It is therefore possible to describe the stated design and groups, but not to reconstruct additional protocol details.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The Pharmacokinetic Per-protocol Set (PK-PPS) was a subset of the Safety Set, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.

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 enrolled participants who received at least 1 dose of Padsevonil (PSL).

6. Primary Endpoint

The registry lists the primary outcome as Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil, measured over Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3).

The primary endpoint is maximum plasma concentration, or Cmax, of padsevonil after a single dose. It is a continuous pharmacokinetic measure expressed in ng/mL. The record defines Cmax as the maximum plasma drug concentration observed among samples collected at predefined time points. Sampling was scheduled predose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose, up to Day 3.

Cmax is used to describe peak measured drug concentration during the sampling period. As a general pharmacokinetic concept, peak concentration can help characterize exposure and compare concentration profiles across groups or dosing conditions. It does not by itself describe the full concentration-time profile, total exposure, duration of exposure, or clinical effects.

The endpoint is specified as a least-squares mean with a 95% confidence interval. A least-squares mean is generally a model-based mean adjusted for terms included in the statistical model; the model terms used for this endpoint are not reported in the registry record. The numerical least-squares mean and confidence interval are also not reported in the registry record. Consequently, the endpoint definition and sampling schedule are available, but the magnitude and precision of the measured peak concentration cannot be assessed from the registry result information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: it records a concentration on a measurement scale rather than counting whether an event occurred. The specified summary is a least-squares mean and its 95% confidence interval. The registry record does not report the fitted statistical model, any covariates, transformations, or the numerical estimates. The interpretation of a least-squares mean therefore has to remain general: it is ordinarily a model-based mean, with adjustment depending on the terms included in the model.

What does a confidence interval communicate?

In general, a confidence interval describes uncertainty around an estimated quantity under the assumptions of the statistical procedure used. A narrower interval indicates greater precision than a wider interval for the same type of estimate. It is not a range guaranteed to contain the true value, and it does not by itself establish that groups differ. Here, the endpoint is specified with a 95% confidence interval, but the registry record does not report its limits. The precision of the Cmax estimate therefore cannot be evaluated.

What can a genotype-group comparison show?

Genotype-defined groups can be used to describe whether pharmacokinetic measurements vary across metabolizer categories. In general, a group comparison should be read alongside the estimate, its uncertainty, and the analysis method. This study is non-randomized, so group membership was not assigned at random. That design is appropriate to describing groups defined by genotype, but it does not create a randomized treatment comparison. The record does not state the statistical method used to compare the genotype groups or report a contrast estimate.

The study is also described as parallel-group. In general, parallel-group designs collect outcomes from separate groups of participants, unlike crossover designs in which participants receive conditions in sequence. The record does not provide further details on how participants were distributed between single-dose and multiple-dose treatment or whether the same participants contributed to more than one listed group. No assumptions about that structure should be added to the reported group counts.

How should planning illustrations be read?

Sample-size calculations based on an observed effect can be used as planning illustrations, but they do not describe the original trial’s design unless the protocol says that they were used for that purpose. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For continuous outcomes, the illustration reports participants per arm for a specified power; time-to-event illustrations instead report a total number of events. These are planning quantities, not observed enrollment requirements, actual trial power, or evidence that the study was designed around those assumptions. The protocol’s sample-size justification is not reported in the registry record.

Because the primary endpoint is continuous, precision and power generally depend on the endpoint’s variability, the effect considered important, the analysis, and the number of observations available. The registry record does not report the variability used in the original design or a protocol-based target for precision. No sample-size justification should be inferred from the enrollment figure alone.

Why does over-dispersion matter in general?

Over-dispersion is a general issue for count outcomes when the observed variability exceeds what a chosen probability model expects. It can make standard errors too small if ignored. It is not a stated feature of this primary endpoint, which is continuous, and the registry record does not describe an over-dispersion analysis. This concept should not be mistaken for a reported method in the study.

The primary endpoint population is the Pharmacokinetic Per-protocol Set. The record defines it as a subset of the Safety Set consisting of participants without important protocol deviations affecting pharmacokinetic parameters and with enough samples to determine at least one pharmacokinetic parameter. This definition matters because an endpoint estimate may be based on a subset rather than everyone enrolled. The size of this analysis population and the handling of missing or unusable samples are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and 15 analyses. It does not report a multiplicity strategy, such as whether any outcomes were designated as confirmatory, whether analyses were arranged hierarchically, or whether significance thresholds were adjusted for multiple testing. The primary endpoint is identified, but that designation alone does not establish how multiplicity was addressed across the other outcomes and analyses. Any formal control of false-positive findings is not reported in the registry record.

The primary endpoint population is the Pharmacokinetic Per-protocol Set, defined as a subset of the Safety Set. Participants were included in that set if they had no important protocol deviations affecting pharmacokinetic parameters and had sufficient samples to determine at least one pharmacokinetic parameter. The number of participants in the PK-PPS is not reported in the registry record. Nor does the record give the number with an evaluable single-dose Cmax value in each metabolizer group.

Missing-data procedures are not reported in the registry record. The record does not specify how missing concentration samples, values below an assay limit, incomplete sampling schedules, or protocol deviations were handled in the primary analysis. It also does not state whether sensitivity analyses were performed. These omissions limit assessment of how the analysis population may differ from the enrolled population and whether missing measurements could affect the endpoint summary. The Safety Set is named in the PK-PPS definition, but its exact membership and analysis rules are not reported.

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 safety entries are organized into six groups: extensive, intermediate, and poor metabolizers, each listed for single-dose and multiple-dose treatment. Each group lists 13 participants at risk. In every listed group, the serious-adverse-event count is 0, while the count for other adverse events is 13. Deaths are listed as 0 in every group, and no top serious-event terms are listed.

These are descriptive registry counts, not a comparison of randomized groups. The study was non-randomized, and the record does not report a control group. The entries do not identify the specific other adverse events, their severity, timing, duration, or relationship to treatment. The registry record also does not provide additional detail on adverse-event collection or coding. Therefore, the counts characterize what is posted, but they cannot explain the nature or clinical importance of the events.

The group counts should be interpreted separately as listed. The registry record does not explain whether participants contributed to more than one group across dosing conditions, so adding group denominators to construct a unique-participant total would not be justified. Zero recorded serious adverse events is not proof that serious events cannot occur; it is a description of the recorded counts in this study.

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

This study addresses a pharmacokinetic question in healthy male Japanese participants grouped by CYP2C19 metabolizer status. Its primary measure, single-dose Cmax, is a way to characterize peak measured plasma concentration. The registry record supplies the endpoint definition, measurement unit, sampling times, and intended summary statistic. It does not report the numerical Cmax estimate or its 95% confidence interval.

As a result, the posted registry information does not quantify padsevonil exposure in the metabolizer groups or show the precision of any estimate. It also does not establish whether Cmax differed across groups. No direction, magnitude, or statistical significance of a group difference can be inferred from the endpoint title or the study’s purpose. A missing numerical result is not equivalent to a finding of no difference.

The safety entries report zero serious adverse events and zero deaths in each listed group, alongside other adverse events affecting all 13 participants at risk in each group. The record does not describe those other events in enough detail to assess their types or severity. These counts should not be treated as evidence that padsevonil is safe or unsafe; they are the recorded observations from the described study groups.

The study is Phase 1, open-label, non-randomized, and single-center. Its participant population is limited to healthy male Japanese participants. Those design features define the scope of the record and do not establish results for other populations or clinical settings. The registry record does not report a clinical outcome, a patient benefit, or a treatment comparison. The information supports a limited account of study design and posted safety counts, while the primary pharmacokinetic result remains unreported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a pharmacokinetic study where the endpoint and sampling schedule are explicit but the numerical primary result is not reported in the registry record. Knowing that Cmax was measured, and how it was defined, is not enough to evaluate the estimate. A point estimate and its confidence interval would be needed to assess both the scale of the peak concentration and the uncertainty around it.

The genotype-based grouping also illustrates why design labels matter. Extensive, intermediate, and poor metabolizers are not randomized arms. A comparison among them can address a descriptive pharmacokinetic question, but it should not be interpreted as a randomized contrast. The non-randomized, open-label structure and the absence of a reported comparison model constrain what can be concluded from group labels alone.

The analysis population is another important statistical detail. The PK-PPS excludes participants with important protocol deviations affecting pharmacokinetics and requires sufficient sampling to estimate at least one parameter. That definition can be appropriate for a pharmacokinetic analysis, but the size of the set and the handling of incomplete sampling are not reported. Without those details, readers cannot fully assess how much data contributed to the primary endpoint.

Finally, the safety counts are group-specific and descriptive. The registry lists serious events and deaths separately from other adverse events, but does not give event types or additional clinical detail. The study therefore illustrates the distinction between a recorded event count and a complete assessment of event patterns. Its statistical value lies in the clearly named pharmacokinetic question and the opportunity to recognize the limits created by unreported estimates and analysis details.

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 for interpreting the primary endpoint is that its numerical estimate and 95% confidence interval are not reported in the registry record. Without them, the magnitude and precision of single-dose Cmax cannot be assessed. The record also does not report a numerical comparison among metabolizer groups, an inferential test, or the statistical model used to generate the stated least-squares mean.

The study is non-randomized and open-label. The metabolizer groups are defined by CYP2C19 genotype rather than randomized allocation, and the record identifies no control group. These features mean that the design should not be read as a randomized comparison. The registry record does not give enough information to examine group comparability or the influence of potential covariates.

The enrolled population was healthy male Japanese participants. The registry record does not report evidence about other populations or clinical settings. The study is also single-center and Phase 1, so the scope of its design is distinct from a trial intended to assess clinical outcomes. The protocol’s dosing details and the relationship between single-dose and multiple-dose participation are not reported.

The PK-PPS definition is available, but its size and the number of evaluable observations are not reported. Missing-data procedures, handling of incomplete sampling, and sensitivity analyses are likewise not reported in the registry record. The record lists 10 outcome measures and 15 analyses but does not state how multiplicity was handled. Safety counts lack descriptions of the other adverse events, their severity, and their relationship to treatment. These gaps prevent a fuller assessment of endpoint robustness and safety-event patterns.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Test the Safety, and Tolerability of Padsevonil in Healthy Male Japanese Study Participants — NCT04075409.
• Registry record last updated 2021-07-08; status last verified 2021-06.
• Results first posted 2021-07-08.
• 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

The registry record describes NCT04075409, a completed Phase 1, open-label, non-randomized, parallel-group, single-center study sponsored by UCB Biopharma S.P.R.L. It enrolled 39 healthy male Japanese participants and examined padsevonil pharmacokinetics, safety, and tolerability in CYP2C19 genotype groups. The study began on 2019-09-30 and reached primary completion on 2019-12-27.

The primary endpoint is single-dose maximum plasma concentration in ng/mL, summarized as a least-squares mean with a 95% confidence interval. The endpoint estimate and interval are not reported in the registry record. Safety entries list 13 participants at risk in each of six genotype-by-dosing groups, zero serious adverse events, 13 participants with other adverse events, and zero deaths in each group. The record lists 10 outcome measures and 15 analyses; multiplicity handling and missing-data methods are not reported.