An Open Label Study of L059 (Levetiracetam) in Japanese Epilepsy Subjects With Generalized Tonic-clonic Seizures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open Label Study of L059 (Levetiracetam) in Japanese Epilepsy Subjects With Generalized Tonic-clonic Seizures (NCT01398956), a na phase 3 study. The primary outcome is Incidence of Treatment Emergent Adverse Events During the Entire Study Period.

2. Clinical Question

The question is primarily descriptive: it concerns safety events observed during ongoing treatment in a selected group of people continuing levetiracetam. Because the study has no concurrent control group, the registry record cannot establish how the observed event counts compare with what would have occurred under another treatment or without this treatment. The record also does not report the primary endpoint result as a number, so the event counts elsewhere in the safety information should not be treated as a reported primary-outcome result.

3. Trial Design

This is a phase 3, open-label, multicenter, long-term follow-up study conducted in Japan. Its official title describes adjunctive oral L059, identified in the record as levetiracetam, for epilepsy subjects with generalized tonic-clonic seizures. The study is marked completed, with an enrollment of 44. The recorded start is 2011-06 and primary completion is 2016-04.

The design is single-group rather than a randomized comparison. Allocation is listed as not applicable, and masking as none. The intervention description specifies oral dosing twice daily, in the morning and evening. The brief summary says investigators would offer treatment to subjects judged to benefit from continued levetiracetam and willing to continue receiving it. This selection is important: the study concerns people chosen for continued treatment, not an unselected group starting therapy under randomized conditions.

The primary outcome is the incidence of treatment-emergent adverse events during the entire study period, with a timeframe described as through completion and an average of 3 years. The listed safety-set definition includes subjects who took at least one dose. Secondary outcomes concern percentage change in generalized tonic-clonic seizure frequency per week over the evaluation period, using a baseline period from either of two previous studies, and the incidence of adverse drug reactions during the entire study period.

The registry record does not report the protocol’s sample-size justification, detailed visit schedule, dose-adjustment rules, or statistical analysis plan. It lists no analyses for the outcome measures. These omissions limit how fully the recorded design can be connected to a formal analysis of treatment effects.

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) which consisted of all subjects who took at least one dose of study medication in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Set (SS) consisted of all subjects who took at least one dose of study medication in this study.

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 Characteristics refer to the Safety Set (SS) which consisted of all subjects who took at least one dose of study medication in this study.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Treatment Emergent Adverse Events During the Entire Study Period, measured over Through study completion, an average of 3 years.

The primary endpoint is the incidence of treatment-emergent adverse events during the entire study period. The record describes the measure as a number of events and defines the observation period as through study completion, an average of 3 years. It defines the safety set as subjects who took at least one dose of study medication.

Safety outcomes are commonly collected to describe what events arise after treatment begins and to identify events that warrant closer review. In a long-term follow-up study, the observation window is relevant because events may be recorded over extended treatment rather than at a single visit. However, an event occurring after treatment starts is not necessarily caused by treatment. A single-group record can describe events during exposure, but without a concurrent comparator it cannot separate treatment effects from the underlying condition, other care, or events that occur over time for other reasons.

The registry lists the primary outcome definition but does not report its result. The adverse-event group information includes counts for serious and other adverse events, but the record does not establish that either count is the reported primary endpoint result. Those categories should therefore be read as safety information, not as a substitute for a missing primary-outcome result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish what a study describes from what it can compare or estimate. In this record, the design is single-group and open-label, and the registry lists no outcome analyses. The most defensible reading is therefore descriptive. The following concepts are general explanations, not claims that a particular analysis was conducted in this study.

What does a single-group design estimate?

A single-group study follows participants receiving a treatment and records outcomes in that group. It can describe the events observed during the observation period, such as counts of people affected or the frequency of a measured outcome. It has no concurrent comparison group to represent what would have happened to similar participants under a different treatment or without the study treatment. Consequently, a within-group observation is not by itself a treatment effect. Changes over time can reflect the course of illness, other care, participant selection, or changes in how events are detected and recorded.

This distinction matters for safety as well as efficacy. An adverse event occurring after treatment begins is temporally associated with treatment exposure, but timing alone does not establish causation. A comparative design can help assess whether event rates differ between treatment strategies, though it too depends on appropriate design and analysis. The current registry description does not offer that comparison.

What is the difference between affected people and events?

In adverse-event reporting, a count of affected participants answers how many people had at least one event in a category. A total event count instead includes repeated events experienced by the same person. Those quantities can differ. The registry safety information records numbers affected for serious and other adverse events, but the primary outcome is described as a number of treatment-emergent adverse events. The record does not clarify that the safety counts are the complete event total for that primary measure. It is important not to equate these measures without an explicit definition.

Event categories may also overlap. A participant could experience events in more than one category or have more than one event. Without participant-level detail and clear rules for categorization, counts across categories should not be added to create a total. The registry record does not provide such detail, so the listed categories are best read individually.

What would a confidence interval mean?

General explanation: a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not resolve biases arising from participant selection, lack of a control group, or differences in event ascertainment. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be assessed from this entry.

Why can event rates be difficult to compare?

General explanation: event-rate comparisons require compatible definitions, observation windows, and populations. Longer follow-up creates more opportunity to observe events than shorter follow-up. Differences in baseline health, treatment history, and monitoring can also change the number of recorded events. A rate using person-time can account for differing time under observation, while a simple proportion does not directly reflect how long each participant was followed. The record describes a study period with an average duration but does not report a person-time analysis or participant-specific follow-up distribution.

Over-dispersion is a general statistical issue that can arise when event counts vary more than a simple count model expects. In such settings, a model that allows extra variability may better reflect uncertainty. This is a general consideration, not a method identified in this registry entry. The statistical plan and analysis details are not reported in the registry record.

What can a planning illustration tell us?

General explanation: sample-size calculations estimate how many participants a future study might need under specified assumptions about the effect to detect, significance level, allocation, and statistical model. They are planning illustrations, not observed power and not results from the current study. The accompanying assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect defined as a fraction of the observed effect. Those assumptions describe a hypothetical two-arm planning exercise. They do not alter the recorded single-group design, and no calculated planning estimates are reported in the registry entry.

Any planning illustration based on an observed effect also depends on the reliability of that effect estimate. If an observed estimate is imprecise, a fraction of it does not remove that uncertainty. A planning estimate should therefore not be mistaken for evidence that the existing study had adequate power or that an effect was established. The registry does not report the trial’s own sample-size justification.

Finally, statistical interpretation depends on prespecified outcomes, analysis populations, missing-data handling, and methods for accounting for multiple outcomes. These details are not reported in the registry record. The absence of those details does not establish that no such procedures existed; it means their role in the posted results cannot be assessed from this entry.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and secondary outcomes concerning seizure-frequency change and adverse drug reactions. It also states that there are 3 outcome measures, but it lists no analyses. The statistical analysis plan, including any approach to multiple comparisons, is not reported in the registry record.

Multiplicity is a general concern when several outcomes or comparisons are examined. The more questions analyzed, the greater the chance that at least one result may appear notable by chance if no adjustment or prespecified hierarchy is used. A prespecified primary endpoint can help distinguish the main question from supporting outcomes, but it does not by itself explain how all analyses were handled. No multiplicity strategy can be inferred from the outcome list alone.

Missing-data procedures are also not reported in the registry record. The entry does not describe whether outcome information was complete for all participants, how missed assessments were handled, or whether participants who discontinued treatment were followed for safety. These details matter because missing observations can affect both the apparent event frequency and the interpretation of seizure-frequency change. A missing-data method cannot be assumed from the study’s long-term follow-up description.

The primary outcome population is the safety set, defined as all subjects who took at least one dose. The registry safety information lists 44 at risk for each of the serious and other adverse-event categories. The record does not describe an efficacy analysis population, an intention-to-treat analysis, or a per-protocol analysis. It also does not report how the outcome analyses treated participants with differing follow-up lengths.

These omissions limit assessment of analysis choices, but they should not be filled by assumption. The registry record establishes the stated endpoint and safety-set definition; further details about multiplicity, missingness, and analysis populations are not reported in 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: influenza (4.5%), acute tonsillitis (2.3%), bronchitis (2.3%), bronchopneumonia (2.3%), pharyngotonsillitis (2.3%).

The safety information lists 44 at risk for serious adverse events, with 13 affected, and 44 at risk for other adverse events, with 41 affected. These are counts in the registry’s safety information. They should be read as descriptive counts, not as evidence that treatment caused the events. The categories should not be added together: the record does not state whether they overlap or whether the same person could appear in both.

The registry lists influenza at 4.5% among the serious-event terms, and acute tonsillitis, bronchitis, bronchopneumonia, pharyngotonsillitis, and pneumonia respiratory syncytial viral at 2.3% each. These percentages describe the listed terms as recorded; the entry does not give details about event duration, recurrence, or how the term-specific rates were derived. It also does not report deaths.

Serious adverse events and other adverse events are not interchangeable categories, and neither category necessarily matches the primary outcome’s full treatment-emergent event count. The primary outcome result itself is not reported in the registry record. Without a comparator, these counts cannot establish whether event occurrence was more or less common than under another treatment or without treatment.

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

The record establishes that a completed, open-label, single-group follow-up study of adjunctive oral levetiracetam was conducted in Japan among epilepsy subjects with generalized tonic-clonic seizures. The described participants were judged by investigators to benefit from continuing treatment and were willing to do so. The primary safety question concerned treatment-emergent adverse events across the study period, described as an average of 3 years.

The registry safety information records 13 affected in the serious adverse-event category and 41 affected in the other-adverse-event category, with 44 at risk in each. It also lists several serious-event terms and their reported rates. These data describe events recorded in the safety group. They do not show that levetiracetam caused those events, nor do they establish a comparative safety profile, because the study has no concurrent control group.

The record does not report the primary outcome result, analyses, confidence intervals, or results for the listed secondary outcomes. Accordingly, it does not support an estimate of the size or precision of a treatment effect on adverse events or seizure frequency. The safety counts should not be substituted for an unreported primary endpoint result, and the secondary seizure-frequency outcome cannot be interpreted without its observed result and analysis details.

The findings also concern a selected group considered appropriate for continued treatment. They should not automatically be generalized to people with different treatment histories or clinical circumstances. In general, descriptive follow-up can contribute information about events observed during ongoing treatment, but conclusions about comparative effects require evidence beyond these single-group counts.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between long-term description and comparative inference. The registry records safety information during continued treatment in a selected group. Such follow-up can document events in the setting in which treatment is used, but the absence of a concurrent comparator limits what the event counts can say about treatment effects.

The distinction between an endpoint definition and an endpoint result is also important. The primary measure is clearly identified as the incidence of treatment-emergent adverse events, with a defined safety-set concept and study-period timeframe. Yet the registry does not report that primary result or an analysis. A well-described outcome question is not, by itself, evidence about the outcome’s magnitude or precision.

The record also illustrates why safety summaries require careful reading. Serious and other adverse-event categories are reported separately, and named serious-event terms have associated rates. Without additional information on overlap, repeated events, and ascertainment, these figures should remain separate descriptive observations rather than being combined into a total or treated as a causal comparison.

For clinical researchers and biostatisticians, the main lesson is to match the strength of a conclusion to the design and reported analysis. The study’s selected population, open-label conduct, single-group structure, and unreported outcome analyses constrain causal and comparative claims. The registry record is useful for identifying the study’s question and reported safety counts, while leaving substantial uncertainty about the primary result and statistical methods.

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 central design limitation is the absence of a concurrent comparator. Allocation is listed as not applicable, masking as none, and the model as single-group. Thus, observed adverse events cannot be contrasted with events under another treatment within this study, and causal attribution is not possible from the recorded counts alone.

The study population is also selected: investigators considered participants appropriate for continued levetiracetam, and participants were willing to continue it. This context differs from a trial enrolling an unselected population at treatment initiation. The record does not provide enough detail to determine how selection may affect the observed safety experience or how broadly it applies to other groups.

The primary endpoint result and all outcome analyses are not reported in the registry record. The entry does not provide confidence intervals, hypothesis tests, adjusted estimates, or detailed event totals for the primary measure. Although the safety information gives counts for serious and other adverse events, it does not establish that these are the full primary endpoint result. Deaths are not reported in the registry record.

Further limitations arise from details that are not reported: the statistical analysis plan, sample-size justification, handling of missing outcomes, participant-specific follow-up, and procedures for multiple outcomes. The record describes an average study duration but does not explain how unequal follow-up was addressed. It also does not clarify whether the serious-event term rates reflect participants, events, or another tabulation rule.

These limitations do not negate the descriptive information in the record, but they restrict inference. The findings should be interpreted as safety observations in the recorded study context, not as a comparative estimate or a complete assessment of treatment effect.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Open Label Study of L059 (Levetiracetam) in Japanese Epilepsy Subjects With Generalized Tonic-clonic Seizures — NCT01398956.
• Registry record last updated 2017-08-15; status last verified 2017-07.
• Results first posted 2017-03-09.
• 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

NCT01398956 is a completed phase 3, open-label, multicenter, single-group follow-up study of adjunctive oral levetiracetam in Japanese epilepsy subjects with generalized tonic-clonic seizures. Enrollment was 44; treatment was taken twice daily, in the morning and evening. The primary outcome was the incidence of treatment-emergent adverse events during the study period, described as through completion with an average of 3 years.

The registry safety information lists 13 affected among 44 at risk for serious adverse events and 41 affected among 44 at risk for other adverse events. It names serious-event terms with reported rates. The primary outcome result, secondary outcome results, outcome analyses, deaths, and statistical analysis plan are not reported in the registry record. Without a concurrent comparator, the event counts are descriptive and do not establish comparative or causal effects.