Pharmacokinetic (PK) Study in Japanese Non-epileptic Renal Impaired Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic (PK) Study in Japanese Non-epileptic Renal Impaired Patients (NCT01491113), a non-randomized phase 4 study. The primary outcome is Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Groups A to D.

2. Clinical Question

3. Trial Design

This was a Phase 4, non-randomized, unmasked, parallel-group study with an enrollment of 30. Its stated purpose was to investigate the pharmacokinetics of a single oral dose of levetiracetam in Japanese subjects with normal renal function and Japanese subjects with various degrees of impaired renal function. The study status is completed. The registry record gives a start date of 2011-11 and a primary completion date of 2012-11.

Groups A to D represented normal, mild, moderate, and severe renal impairment, respectively. Group A received 500 mg once, as did Group B. Groups C and D received 250 mg once. Their scheduled safety assessments and blood and urine sampling extended through Day 4, Day 5, Day 6, and Day 7, respectively. The record also describes Group E as end-stage renal disease. Its regimen included 500 mg on Day 1, 44 hours before the first hemodialysis, followed by a supplementary 250 mg dose 1 hour after the end of the first hemodialysis on Day 3. It describes the hemodialysis as 4-hour hemodialysis.

The non-randomized design means renal-function categories were not created through random assignment. The different doses and observation windows also matter when interpreting between-group pharmacokinetic patterns. The registry record explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The reason for the particular group sizes, dose assignments, and observation periods is not reported in the registry record. A sample-size justification is not reported in the registry record.

The record lists 29 outcome measures and zero posted analyses. The primary endpoint applies to Groups A to D; secondary outcomes include urinary excretion and clearance measures for Groups A to D, and a clearance measure for Group E during the first period. This outcome structure indicates a descriptive pharmacokinetic focus across renal-function groups, rather than a confirmatory randomized comparison.

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: About 30 (28 to 30) subjects were planned to be enrolled for 5 groups (A to E) according to their renal function based on the value of creatinine clearance (CLCr).

Overall Study

Analysis population for the primary outcome, as defined in the registry: The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters.

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 Baseline Analysis Population refers to the Pharmacokinetic Per Protocol Set (PK-PPS) which consists of all subjects included in the Safety Set (SS), who also had a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the PK parameters.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Groups A to D, measured over From Baseline up to 144 hours post first dose.

The primary endpoint is maximum observed plasma concentration, or Cmax, of Ucb L059 (levetiracetam) for Groups A to D. Cmax is the highest measured concentration in plasma over the observation period. In general, it is used to describe the peak concentration reached after administration and is one component of a drug’s concentration-time profile. It is not, by itself, a complete description of total drug exposure or the time course of concentration.

The registry record specifies a geometric mean as the primary summary and a geometric coefficient of variation as the measure of dispersion. In general, geometric summaries are used for data that are positive and may be right-skewed; the geometric coefficient of variation describes relative variability on a multiplicative scale. These summaries can help characterize the distribution of measured concentrations without implying that the group averages are treatment effects.

The listed timeframe is baseline through 144 hours after the first dose, while the endpoint description gives group-specific windows: baseline to 72 hours for Group A, baseline to 96 hours for Group B, baseline to 120 hours for Group C, and baseline to 144 hours for Group D. These unequal windows mean the periods over which the maximum could be observed were not the same across groups. The registry record does not report numerical Cmax estimates, their dispersion, or confidence intervals. Consequently, the direction and precision of any between-group pattern in this primary endpoint cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information in the registry record is most useful for clarifying what was measured and how the study groups were formed. It is not a complete statistical analysis plan. The record describes a non-randomized, unmasked, parallel study and defines the primary pharmacokinetic outcome, but it does not report the statistical tests, model specifications, covariate adjustments, or procedures for handling missing values. Those details are not reported in the registry record.

What does Cmax describe?

Cmax is the maximum observed concentration in plasma during the specified sampling period. It summarizes the peak of the measured concentration-time profile, rather than the full exposure profile. Because the endpoint depends on observed samples, the timing and frequency of sampling can influence the maximum that is captured. The registry record states that blood and urine sampling took place after dosing, with the observation period differing by group. It does not provide the individual sampling schedule or numerical concentration-time data.

The primary endpoint is summarized using a geometric mean and a geometric coefficient of variation. In general, the geometric mean is a suitable summary for positive measurements whose distribution is better represented on a logarithmic scale than by an arithmetic average. The geometric coefficient of variation expresses variability in relation to the geometric mean. These are descriptive summaries: they do not, by themselves, establish that groups differ or quantify uncertainty in a contrast. Confidence intervals, if reported, would help show the range of values compatible with the data under the analysis assumptions, but confidence intervals for the primary endpoint are not reported in the registry record.

Why does the group structure matter?

The renal-function groups were not randomized. In addition, the dose is not the same for every group, and the Cmax observation windows differ. General statistical interpretation of non-randomized group comparisons must account for the possibility that groups differ in features other than the factor being studied. Here, a between-group contrast cannot automatically be attributed to renal function because dose and observation period also vary. The record does not report an adjusted analysis that would address such differences.

The study is described as parallel, meaning the registry organizes participants into distinct study groups rather than reporting a crossover comparison. The groups correspond to renal-function categories and a separate end-stage renal disease group. The record does not say that participants were randomly allocated to these categories; indeed, allocation is listed as non-randomized. The group labels therefore describe the study structure, not randomized treatment arms.

What is the analysis population?

The primary analysis population is the Pharmacokinetic Per Protocol Set. The record defines it as subjects included in the Safety Set who also had a sufficient number of bioanalytical assessments, in plasma or urine, to calculate reliable pharmacokinetic parameters. This definition links inclusion in the pharmacokinetic analysis to availability and adequacy of measurements. The number analyzed in that population, and the number excluded from it, are not reported in the registry record. The enrollment figure should not be treated as the number contributing to every endpoint.

How should planning calculations be read?

The registry record describes planning illustrations computed from an observed effect. It specifies 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. In general, such calculations translate an assumed effect and analysis framework into a planning requirement. They are not observed power and do not show the probability that the study detected a real effect after the data were collected. The illustrations are especially limited when the observed effect estimate and its underlying analysis are not reported alongside the registry results.

The record's planning description says that time-to-event calculations use total events, while other calculations use participants per arm. This study's listed primary endpoint is a pharmacokinetic measure, not a time-to-event outcome. No numerical planning requirements are reported in the registry record, and the study's own sample-size justification is not reported in the registry record. The illustrations should therefore be read as planning scenarios, not as a description of the enrollment rationale or a finding from the trial.

What does the absence of posted analyses imply?

The registry record lists zero analyses. This indicates that inferential results are not posted in the record; it does not establish that investigators conducted no analyses. The record also does not report p-values, confidence intervals, model estimates, or adjusted contrasts for the primary outcome. General statistical interpretation depends on estimates and their uncertainty, not just on naming an endpoint or summary measure. Without those results, a quantitative assessment of the strength or precision of any pattern is not possible from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 29 outcome measures, including a primary Cmax outcome and secondary outcomes covering urinary excretion and clearance. It does not report how multiplicity was addressed. In general, when multiple outcomes or comparisons are examined, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of tests. The record does not state whether outcomes were tested inferentially, whether any adjustment was planned, or whether a hierarchy among secondary outcomes was used. Those details are not reported in the registry record.

The record lists zero analyses, and numerical results for the primary and secondary outcomes are not reported in the registry record. It therefore is not possible to assess how many comparisons were actually made, whether analyses followed a prespecified plan, or how multiplicity might affect interpretation. The registry describes the outcome measures, but does not provide a statistical analysis plan or identify interim analyses. Any interim-analysis plan is not reported in the registry record.

Missing-data handling is also not described. For the pharmacokinetic analysis, the defined population required a sufficient number of bioanalytical assessments to calculate reliable estimates. This eligibility rule indicates that measurement availability was relevant to inclusion, but the record does not report how many subjects lacked adequate assessments, how missing concentration measurements were handled, or whether any imputation or sensitivity analysis was used. Those details are not reported in the registry record.

The registry specifies the Pharmacokinetic Per Protocol Set as the primary analysis population and relates it to the Safety Set and adequate bioanalytical data. It does not report the number analyzed for the primary outcome or give an analysis population for each secondary outcome. Enrollment and analysis counts should therefore not be assumed to match. The extent to which exclusions or missing measurements could affect the reported pharmacokinetic summaries cannot be assessed from the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (16.7%), acute respiratory distress syndrome (16.7%), shunt malfunction (16.7%).

The registry lists serious and other adverse-event counts separately for Groups A to E. For serious adverse events, the number at risk is 6 in each group. The serious-event count is 0 in Groups A, B, C, and D, and 1 in Group E. For other adverse events, the number at risk is 6 in each group; the counts are 0 in Group A, 2 in Group B, 0 in Group C, 1 in Group D, and 2 in Group E. These are descriptive counts in the registry record, not a randomized comparison of safety outcomes.

The listed serious-event terms are pneumonia, acute respiratory distress syndrome, and shunt malfunction, each reported as 16.7%. The record does not connect those terms to particular groups in the information, so they should not be assigned to a group based on the group-level counts. Death counts are not reported in the registry record; the record lists them as unavailable rather than giving a zero count.

In general, adverse-event counts describe events recorded in the study, while their interpretation depends on definitions, follow-up, and the population assessed. The registry describes a short, single-dose pharmacokinetic study with group-specific assessment periods. These counts do not establish comparative risk, and the small group-level denominators do not support treating absence of a recorded event as proof that an event cannot occur. The record does not provide event-level timing, severity details beyond the serious classification, or a comparative statistical analysis.

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

The registry record establishes that a Phase 4 pharmacokinetic study was conducted in Japanese subjects with normal renal function and varying degrees of renal impairment. It describes single-dose levetiracetam regimens for Groups A to D and a separate dosing schedule around hemodialysis for Group E. It also identifies Cmax as the primary outcome for Groups A to D and lists additional urinary excretion and clearance outcomes.

That information describes the question and study structure, but it does not answer the question quantitatively. Numerical primary-endpoint results are not reported in the registry record. Neither the group-specific geometric means nor their geometric coefficients of variation are available in the record, and there are no posted analyses. It is therefore not possible to state from this record how Cmax varied across the renal-function groups or how precisely any difference was estimated. Numerical results for the listed secondary pharmacokinetic outcomes are also not reported in the registry record.

The study's non-randomized structure also constrains interpretation. Groups were defined by renal function, and their doses and observation windows differed. Thus, any group pattern would be descriptive unless the analysis addressed the design and relevant differences; the registry record does not report such an analysis. Group E had a distinct regimen involving hemodialysis, and the primary outcome is specified for Groups A to D, so the Group E information should be interpreted separately.

In general, pharmacokinetic measurements can describe concentrations and drug handling under the studied conditions. They do not, on their own, establish a clinical benefit or harm. This record is not a randomized clinical outcome comparison, and no clinical effectiveness outcome is identified as the primary question. The reported safety counts are descriptive, with serious and other adverse events recorded by group; they do not provide a controlled estimate of comparative risk.

The most defensible conclusion is that the registry documents the study design, endpoints, analysis-population definition, and adverse-event counts, but does not report the numerical pharmacokinetic findings needed to judge the size or precision of the primary result. The absence of those results in the registry record should not be recast as evidence of no difference or no effect.

13. Why This Trial Matters Statistically

This study matters statistically because pharmacokinetic comparisons across renal-function categories are not straightforward when dose and observation windows vary by group. The design makes those details central to interpretation: Groups A and B received 500 mg once, Groups C and D received 250 mg once, and their Cmax observation periods were not equal. The registry also describes a distinct regimen for Group E around hemodialysis. Recognizing these design features is necessary before interpreting any apparent group pattern as a renal-function association.

The study also illustrates why endpoint definitions and analysis populations matter. Cmax is a peak concentration summary, and the registry specifies a geometric mean and geometric coefficient of variation. The primary analysis population required adequate bioanalytical measurements. These choices shape what is summarized and who contributes to the estimate. The registry record gives the population definition but not the number analyzed or the endpoint values, leaving important questions about precision and missing measurements unanswered.

Another statistical lesson is the distinction between a planning calculation and an observed result. The record describes planning illustrations based on fractions of an observed effect, but these are not observed power and cannot replace the missing estimates or uncertainty measures. A planning scenario communicates assumptions about a future design; it does not show that an effect was detected.

Finally, the record lists many outcome measures but no posted analyses. Without results or a stated multiplicity strategy, readers cannot evaluate the pattern across the primary and secondary outcomes. The case underscores that a registry entry can clarify intended measurement and study structure while still leaving the statistical evidence unavailable. Clear reporting of estimates, variability, analysis populations, and analysis methods is necessary for readers to assess what the data support.

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 posted results is that numerical values for the primary Cmax endpoint are not reported in the registry record. The geometric means, geometric coefficients of variation, and uncertainty estimates are absent. Numerical results for the listed secondary outcomes are also not reported. Although the record lists 29 outcome measures, it lists zero analyses, so readers cannot assess the reported statistical evidence or compare endpoint results.

The study was non-randomized and the record cautions that its arms are not like-for-like control comparisons. Groups differed in renal-function category, dose, and Cmax observation window. Any group differences would therefore need cautious interpretation, and the registry record does not report an adjusted analysis to address these design features. Group E's hemodialysis-related regimen is distinct from the regimens for Groups A to D, while the primary Cmax outcome is specified only for Groups A to D.

The analysis population is defined by inclusion in the Safety Set and adequate bioanalytical assessments, but the number included in each pharmacokinetic analysis is not reported in the registry record. The amount and handling of missing data are also not reported. It is not possible to determine from the record whether missing measurements or analysis-population exclusions affected the results.

The statistical analysis plan, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record. The adverse-event counts are descriptive, and the record does not provide a comparative safety analysis. Death counts are not reported in the registry record. These limitations do not establish that analyses or procedures were absent; they identify information that the registry record does not report.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetic (PK) Study in Japanese Non-epileptic Renal Impaired Patients — NCT01491113.
• Registry record last updated 2014-02-10; status last verified 2014-01.
• Results first posted 2014-01-10.
• 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

NCT01491113 is a completed Phase 4, non-randomized, unmasked, parallel pharmacokinetic study with an enrollment of 30. It examined single-dose oral levetiracetam in Japanese subjects across renal-function groups, with a separate regimen for end-stage renal disease around hemodialysis. The primary outcome was maximum observed plasma concentration for Groups A to D, summarized using a geometric mean and geometric coefficient of variation.

The registry record defines the Pharmacokinetic Per Protocol Set and lists 29 outcome measures, but it lists zero analyses and does not report numerical results for the primary or secondary pharmacokinetic outcomes. Serious and other adverse-event counts are reported by group, while death counts are not reported in the registry record. The non-randomized design, varying doses, and group-specific observation windows limit direct interpretation of between-group patterns.