A Long Term Follow up Administration Study of L059 (Levetiracetam) in Epilepsy Patients With Partial Onset Seizures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Long Term Follow up Administration Study of L059 (Levetiracetam) in Epilepsy Patients With Partial Onset Seizures (NCT00367432), a na phase 3 study. The primary outcome is Occurrence of Treatment-emergent Adverse Events During the Study Period (Until the Time of Approval Granted).

2. Clinical Question

This is a long-term follow-up question, not a direct comparison of levetiracetam with another treatment. Its primary endpoint is a participant count: whether a participant had at least one treatment-emergent adverse event during the specified period. The endpoint definition does not require that an event be judged caused by levetiracetam. The registry record defines an adverse event as an untoward medical occurrence in a participant who received a pharmaceutical product, whether or not it has a causal relationship with that product.

The record also lists secondary seizure-frequency and response outcomes for an initial 16-week period in this study. Those outcomes refer to seizure frequencies and baselines from an earlier study. However, no analyses are listed, and numerical results for those outcomes are not reported in the registry record. The available information therefore describes the study questions and design, but does not establish how seizure outcomes changed during follow-up.

3. Trial Design

This was a phase 3, multicenter, open-label, long-term follow-up study of levetiracetam in people with epilepsy and partial-onset seizures. Participants were 16 to 65 years old and had completed a previous study. The study is recorded as single-group, with no masking and no randomized allocation. Enrollment was 398. The sponsor was UCB Japan Co. Ltd.

The intervention was levetiracetam tablets taken orally twice daily, in the morning and evening. The dose was individually selected within a range of 500 to 3000 mg/day. The planned study period continued until the time of approval granted. The primary endpoint timeframe is described as beginning at Visit 1 (Week 0) and ending at the follow-up visit, up to Month 60 and until the time of approval granted. The registry record does not specify each participant’s actual follow-up duration.

The study began in 2006-07, had a primary completion date of 2010-12, and is marked completed. These dates describe the study record; they do not by themselves indicate how long any individual participant was followed. The brief description says the study was intended to evaluate long-term safety and efficacy among people who completed earlier studies. The record lists earlier studies N01020 and N01221, while its safety-population description also refers to N01020 and N01221.

There is no concurrent control group, so outcomes are observed in a treated follow-up cohort rather than compared between randomized groups. Open-label treatment also means masking was not used. These design features are important when interpreting adverse-event counts and any seizure outcomes: observed events or changes cannot be attributed to treatment by a controlled contrast on the basis of this design alone. A sample-size justification, detailed allocation procedure, and further protocol details are not reported in the registry record.

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: Eligible subjects from preceding study N01221 \[NCT00280696\] entered the First Period of this study and those subjects from N01221 \[NCT00280696\] who completed the First Period and subjects from the study N01020 \[NCT00160615\] entered the Second Period. Participant Flow and Baseline Characteristics refer to the FAS.

First Period (16 Weeks)

Reasons for not completing this period:

Second Period (up to 54 Months)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Set includes all subjects from N01221 \[NCT00280696\] and N01020 \[NCT00160615\] administered the investigational products at least once.

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.

6. Primary Endpoint

The registry lists the primary outcome as Occurrence of Treatment-emergent Adverse Events During the Study Period (Until the Time of Approval Granted), measured over During the study period from Visit 1 (Week 0) to the Follow-up Visit (up to Month 60) until the time of approval granted.

The primary endpoint is the number of participants with at least one treatment-emergent adverse event during the study period. Its timeframe runs from Visit 1 (Week 0) to the follow-up visit, up to Month 60 and until the time of approval granted. The endpoint is reported as a count of participants, rather than a count of all events or a rate per unit of follow-up.

An adverse event is defined in the record as an untoward medical occurrence in a participant administered a pharmaceutical product; it need not have a causal relationship with that product. “Treatment-emergent” identifies the endpoint’s event category, but the registry record does not provide further operational rules for determining when an event qualified or how event onset was handled.

Counting participants with at least one event is a way to describe how many people experienced an event during the specified observation period. It can give a direct summary of participant-level event occurrence, but it does not describe the number of events each person experienced, their duration, severity, or timing. Nor does an event count alone establish that treatment caused an event. In a single-group follow-up study, there is no concurrent untreated or active-control group to provide a randomized comparison.

The endpoint is designated primary, but its numerical result and any uncertainty estimate or statistical test are not reported in the registry record. The listed safety population includes participants from earlier studies who received investigational product at least once. The record does not report a separate primary-endpoint analysis population, handling of incomplete follow-up, or a statistical method for this outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s primary outcome is a participant-level binary outcome: a participant either had at least one treatment-emergent adverse event during the defined study period or did not. Reporting the number of affected participants summarizes how many people met that criterion. It does not count repeated events separately, and it is not the same as an event rate based on person-time. The registry record supplies counts for safety categories but does not post a full statistical analysis of the primary endpoint.

What does a participant count communicate?

A count is straightforward to describe, but its interpretation depends on the population and observation period. Here, the safety population is defined as participants from earlier studies who received investigational products at least once. The primary endpoint period is described as extending from Visit 1 (Week 0) to a follow-up visit, up to Month 60 and until the time of approval granted. The registry record does not report an individual-level follow-up distribution or an adjustment for differing observation time. Consequently, the listed number of participants affected does not by itself communicate the rate at which events occurred.

For a binary outcome, an analysis might report a proportion, a confidence interval, or a test against a specified comparison. Those are general statistical options, not methods reported for this endpoint. No such analysis is listed in the registry record. No estimate of uncertainty for the primary endpoint is posted, so its statistical precision cannot be evaluated from the record.

Why does the design matter?

General explanation: a randomized comparison uses allocation to create groups that can be compared under the trial design. In this study, allocation is listed as not applicable, masking is absent, and the model is single-group. There is no contemporaneous comparison arm. Therefore, the recorded counts are descriptive observations in a treated cohort, not an estimate of the difference between levetiracetam and a control treatment. A before-and-after comparison, if available, would also need to account for the fact that this cohort entered after completing an earlier study. The registry record does not report a statistical method for such a comparison.

Open-label means masking was not used. General explanation: knowledge of treatment can affect reporting, assessment, or clinical management, depending on the outcome and study procedures. The registry record does not describe safeguards or assessment procedures that would allow those possibilities to be evaluated. This is a design consideration, not evidence that a particular event was misclassified.

What is the role of secondary outcomes?

The record lists nine outcome measures and identifies secondary seizure-frequency and response outcomes. These include weekly frequency during the first 16-week period, a response definition based on at least a 50% reduction from baseline in N01221, and changes in different partial-seizure categories. The registry record lists no analyses. It does not post numerical results, estimates, uncertainty intervals, or testing procedures for these outcomes. Thus, the outcome definitions can be described, but their observed values and statistical interpretation are not available from the record.

When many outcomes or comparisons are examined, multiplicity can increase the chance of a misleading positive finding if results are interpreted without accounting for the number of tests. General statistical approaches can include prespecifying a primary outcome, adjusting tests, or treating secondary findings as exploratory. The registry record does not report a multiplicity procedure or a detailed analysis plan. With no posted analyses, the impact of multiplicity on reported inference cannot be assessed.

What does a sample-size illustration mean?

General explanation: planning calculations can estimate how many participants per arm might be needed to detect an assumed effect under stated statistical assumptions. Such calculations depend on the outcome, effect size, variability, significance level, allocation, and analysis method. They are planning illustrations, not evidence that a study had a particular probability of success after it was completed. The registry record does not report its own sample-size justification, and it lists no statistical analyses from which an observed treatment effect could be assessed. No sample-size conclusion about this study’s adequacy can be drawn from the posted information.

The record’s description of a planning illustration specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect defined as a fraction of an observed effect. Those assumptions describe an illustration, not the design of this single-group study. The study has no two-arm randomized comparison in the registry record, and no numerical illustration results are reported in the information available for interpretation. They should not be mistaken for an observed power calculation or a trial-specific design justification.

Overall, the statistical information supports a limited description of the study design and safety counts. It does not include a reported primary endpoint analysis, uncertainty estimates, a test, or a model. General statistical principles can clarify what those missing elements would mean, but they cannot supply study-specific results absent from the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Levetiracetam")
n      <- c(398)
events <- c(381)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Levetiracetam  398  381  95.7  93.2  97.5  93.3  97.3  93.3  97.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists nine outcome measures, including a primary safety outcome and secondary seizure-frequency and response outcomes. It lists zero analyses. No numerical results or inferential tests for the listed seizure outcomes are reported in the registry record. A planned hierarchy among secondary outcomes, a multiplicity adjustment, and a rationale for the number of outcomes are not reported in the registry record.

General explanation: when several outcomes are tested, the chance of finding at least one apparently positive result can rise unless the analysis plan accounts for multiple testing. Adjustments or a clear distinction between confirmatory and exploratory outcomes can help readers interpret results. Here, no analysis procedures are posted, so it is not possible to determine whether multiplicity was addressed. Because no outcome analyses are listed, there are no reported p-values to evaluate in that context.

The safety population is described as participants from N01221 and N01020 who received investigational products at least once. The record does not report how missing outcome data, incomplete follow-up, withdrawals, or participants with unavailable seizure diaries were handled. It also does not report whether the primary endpoint analysis used all participants in the safety population or a different analysis population.

Interim analyses and stopping rules are not reported in the registry record. A detailed statistical analysis plan, including model choice, covariate adjustment, event coding rules, and methods for incomplete data, is also not reported. These absences mean that the reported safety counts can be read descriptively, but the record does not permit evaluation of analysis choices or their potential effects on statistical inference.

12. 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: epilepsy (1.3%), status epilepticus (1.3%), pneumonia (1.0%), anticonvulsant toxicity (0.8%), skin laceration (0.8%).

The safety record lists 64 participants affected by serious adverse events among 398 at risk, and 369 participants affected by other adverse events among 398 at risk. These are counts of participants, not counts of all events, and the categories should be read as reported rather than interpreted as a comparison between treatments. The record does not provide a concurrent control group.

The listed serious adverse-event terms and percentages are Epilepsy, 1.3%; Status Epilepticus, 1.3%; Pneumonia, 1.0%; Anticonvulsant Toxicity, 0.8%; Skin Laceration, 0.8%; and Abortion Induced, 0.5%. These selected entries do not describe every event or show how often an individual participant experienced repeated events. The registry record does not report deaths. It also does not provide enough detail to infer causal attribution from these terms or to compare event risk with another treatment.

General explanation: serious adverse events are a safety classification, while an adverse event is a broad report of an untoward medical occurrence. The record’s primary endpoint counts participants with at least one treatment-emergent adverse event, and it does not require a causal relationship with treatment. Interpretation should therefore distinguish recorded occurrence from evidence that treatment caused an event.

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

The registry record describes a completed, open-label, single-group follow-up study of levetiracetam in people with partial-onset seizures who had completed an earlier study. It identifies treatment-emergent adverse events as the primary endpoint and provides some safety counts. It does not post a numerical result or statistical analysis for the primary endpoint, and it lists no analyses. Numerical results for the secondary seizure outcomes are not reported in the registry record.

The safety counts document participants recorded as affected by serious and other adverse events. They do not, on their own, establish whether events were caused by levetiracetam. The primary endpoint definition explicitly includes events whether or not they have a causal relationship with the pharmaceutical product. No randomized control group is available to estimate what event occurrence might have been under a different treatment. Consequently, the record does not support a comparative safety conclusion.

The study’s long-term follow-up purpose is relevant to describing events observed during continued treatment, but the registry record does not specify actual follow-up duration for each participant. Counts accumulated over a period that could extend up to Month 60 should not be treated as if every participant had identical observation time. The record does not report a person-time analysis or another adjustment for different follow-up.

The secondary outcomes describe questions about seizure frequency and response during the first 16-week period. Without posted numerical results, it is not possible to describe the direction or magnitude of any change, or how precisely a change was estimated. The fact that an outcome was specified does not mean its result is available or that a treatment effect was established.

In general, a study result can support an inference only to the extent that the design, measurements, analysis, and uncertainty estimates allow. Here, the available information supports a description of the design and listed safety observations. It does not establish efficacy, a causal effect, or comparative risk. Those conclusions would require evidence and analyses not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable as a long-term, single-group follow-up rather than a randomized comparison. Its design frames the data as observations among participants continuing into follow-up after earlier studies. That makes the distinction between descriptive safety information and a comparative treatment effect central to interpretation.

The primary endpoint is participant-level occurrence of at least one treatment-emergent adverse event over an extended study period. This endpoint offers a direct way to record whether participants experienced an event, while leaving other questions—such as event frequency, timing, recurrence, duration, and causal attribution—unanswered unless additional analyses are reported. The registry record does not post those analyses.

The study also illustrates why an outcome definition and an outcome result are different things. Several secondary seizure measures are specified, including seizure frequency and response status, but numerical results and analyses are not listed. The presence of defined outcomes alone cannot indicate whether they changed or how precisely a change was estimated.

Enrollment of 398 and the listed safety counts give descriptive context, but without a concurrent comparison group, a detailed statistical analysis, and uncertainty estimates, they cannot establish relative effects. The absence of a reported sample-size justification or analysis plan further limits assessment of how the study was intended to support statistical inference.

For biostatistical interpretation, the important lesson is to keep the design, endpoint, and available analysis aligned: counts from an uncontrolled follow-up can describe recorded events, but they cannot by themselves answer a comparative causal question. The registry record leaves efficacy analyses and several details of safety analysis unreported, so conclusions should remain bounded by the information it records.

15. 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 main limitation for interpretation is the absence of a randomized comparator. The study is listed as single-group, open-label, and without masking. Its safety counts therefore describe events recorded among treated participants, not differences against a concurrent control group. They cannot isolate treatment effects from other explanations for events or changes over time.

The registry record does not post a numerical result or statistical analysis for the primary endpoint. It also lists no analyses for the secondary seizure outcomes. Consequently, estimates of treatment effect, statistical uncertainty, and outcome-specific results cannot be assessed. The listed adverse-event counts do not include an inferential comparison or a reported confidence interval.

Follow-up is described as continuing to the follow-up visit, up to Month 60 and until the time of approval granted, but actual participant-level follow-up duration is not reported in the registry record. The record does not report an event rate adjusted for time at risk, or explain how incomplete follow-up was handled. It also does not report withdrawals, missing outcome data, or methods for dealing with unavailable seizure-frequency information.

Additional protocol and analysis details are not reported in the registry record. These include a sample-size justification, detailed statistical analysis plan, interim analyses, multiplicity methods, and further procedures for defining or coding endpoint events. The record also does not provide event-level detail sufficient to assess timing, recurrence, or causal attribution for the selected serious adverse-event terms.

These limitations do not negate the descriptive information that is posted, but they constrain what can be inferred from it. The study can be described as a long-term follow-up with recorded safety counts; the record does not support a quantitative claim about comparative safety or efficacy.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Long Term Follow up Administration Study of L059 (Levetiracetam) in Epilepsy Patients With Partial Onset Seizures — NCT00367432.
• Registry record last updated 2020-11-13; status last verified 2015-04.
• Results first posted 2012-01-16.
• 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.

19. Record Summary

NCT00367432 is a completed phase 3, multicenter, open-label, single-group follow-up study of levetiracetam in people with partial-onset seizures who completed an earlier study. Enrollment was 398. The study began in 2006-07 and had a primary completion date of 2010-12. Participants received oral tablets twice daily at an individual dose ranging from 500 to 3000 mg/day.

The primary endpoint was the number of participants with at least one treatment-emergent adverse event during the study period, up to Month 60 and until the time of approval granted. The safety record lists 64 participants affected by serious adverse events and 369 affected by other adverse events, among 398 at risk. It lists no analyses. Numerical results for the primary endpoint and secondary seizure outcomes are not reported in the registry record. The study has no concurrent randomized comparator, so the posted counts are descriptive rather than estimates of comparative treatment effects.