Open Label Safety and Efficacy Study of Levetiracetam in Patients With Epilepsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open Label Safety and Efficacy Study of Levetiracetam in Patients With Epilepsy (NCT00160654), a na phase 4 study. The primary outcome is Number of Patients With Adverse Events (AEs).

2. Clinical Question

The study was designed to assess safety and efficacy of levetiracetam used as adjunctive therapy in adult subjects with uncontrolled partial epilepsy. Its primary endpoint concerned safety: the number of participants with adverse events during the specified observation period. The registry also lists seizure-frequency and response outcomes, but numerical results for those outcomes are not reported in the registry record.

These features frame what the results can address. A single-group safety count describes events recorded among participants during the study; it cannot by itself distinguish treatment-related events from events that would have occurred for other reasons. The registry lists six secondary outcomes involving seizure-frequency changes, response categories, illness severity, and retention. Their outcome values are not reported in the registry record, so the clinical question about efficacy cannot be answered from the numerical results recorded.

3. Trial Design

This was a Phase IV, open-label, multicenter, community-based study in Asia. The registry describes it as a single-group trial of levetiracetam in adults with uncontrolled partial epilepsy. Enrollment was 251. The recorded study start was 2003-11-24, primary completion was 2006-12-12, and status is completed.

Participants received open-label levetiracetam as adjunctive therapy. The registry summary says the optimal dose in daily clinical practice would be used; the actual dosing schedule, dose range, titration approach, and duration of individual treatment are not reported in the registry record. The title uses the brand name Keppra, while the registered intervention is levetiracetam.

Allocation is listed as not applicable, masking as none, and the model as single group. Thus, the design did not assign participants to separate randomized treatment arms, and there was no masked comparison group. The registry’s study description does not identify a concurrent control or a placebo group. This matters when interpreting observations: changes over time and event counts can be described, but the design does not isolate a treatment effect against a randomized comparator.

The primary endpoint was the number of participants with adverse events from baseline until the safety visit, which was scheduled two weeks after the last dose and up to Week 18. The registry lists six secondary outcomes: changes in partial-seizure and total-seizure frequency, 50% and 100% response at Week 16, categorized change in severity of illness, and retention at Week 16. Numerical results for these secondary outcomes are not reported in the registry record.

Enrollment is not the same as the number completing every assessment. Participant flow, withdrawals, adherence, and analysis populations are not reported in the registry record. The protocol’s sample-size justification, detailed statistical plan, and any interim analyses are also 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: Participant Flow refers to the Intend-to-treat (ITT) Set.

Overall Study

Reasons for not completing this period:

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 Intend-to-treat (ITT) Set.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Adverse Events (AEs), measured over From Baseline until Safety visit (two weeks after last dose; up to Week 18).

The primary endpoint is the number of participants with adverse events during the period from baseline until the safety visit, defined as two weeks after the last dose and up to Week 18. The registry’s definition covers an untoward medical occurrence in a participant who has received a pharmaceutical product; it explicitly does not require a causal relationship with treatment. The endpoint is therefore a measure of observed safety events, not a count restricted to events judged to have been caused by levetiracetam.

In general, a participant count is a straightforward way to describe how many people experienced at least one event during an observation period. It is different from counting every event episode: one participant may have more than one event, and the number of participants affected does not reveal how often events recurred. The record does not report an overall numerical result for the primary endpoint as titled. It does separately list 15 participants with serious adverse events and 136 with other adverse events, each among 251 at risk.

Safety endpoints are useful in a study intended to record adverse events during treatment, particularly when they are reported alongside the observation period and the number of participants at risk. However, because this study has one open-label group, the counts describe events observed in that group rather than a comparative excess over another treatment or control. The registry does not report causal assessments or an overall risk estimate with a confidence interval for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a study with one open-label treatment group and a primary endpoint expressed as a number of participants. The posted safety summaries are counts of participants affected, with 251 listed at risk for each category. The record does not report an inferential analysis of the primary endpoint or numerical results for the listed secondary outcomes.

What does a participant count represent?

In general, a count of participants with an event answers how many people experienced the event at least once during a defined period. It is not necessarily the same as the number of event episodes. If one participant experiences several episodes, a participant-level count still records that person once for the affected-participant outcome. A count also depends on the population observed and the period used to identify events, so the endpoint’s timeframe is part of its interpretation.

Here, the primary endpoint is defined over a period beginning at baseline and continuing until the safety visit, two weeks after the last dose and up to Week 18. The registry provides separate serious and other adverse-event counts, but the overall primary endpoint count is not reported in the registry record. It also does not provide details on repeat events or the handling of participants with incomplete follow-up.

What can an uncontrolled design estimate?

In general, a single-group study can describe observations in the people who received the intervention. Without a concurrent comparator, it cannot estimate a between-group contrast. In an open-label study, participants and study personnel are not masked to the intervention, and the registry lists masking as none. Event reporting and clinical assessments may be influenced by knowledge of treatment, although the registry does not report whether or how this occurred in this study.

The registry lists allocation as not applicable and the model as single group. There is therefore no randomized comparison in which chance allocation helps balance participant characteristics between treatment arms. A before-and-after outcome may be informative descriptively, but changes could also reflect factors other than treatment. No such numerical efficacy results are reported in the registry record.

How should the serious-event terms be read?

The record lists six serious-event terms with percentages. In general, a term-specific percentage describes the proportion or frequency represented by that term according to the registry’s reporting convention. The convention and calculation details are not reported in the registry record, so the listed percentages should be quoted as reported rather than reinterpreted. The terms cannot be summed to obtain a count of unique participants unless the record establishes that categories are mutually exclusive; it does not do so.

The registry reports an adverse-event definition that does not require a causal relationship to treatment. As a result, these listings describe events recorded during the study and do not, by themselves, attribute those events to levetiracetam. The record does not report case narratives, causality assessments, or a comparative analysis.

What do uncertainty and statistical significance add?

In general, an estimate is more informative when paired with a measure of uncertainty. A confidence interval indicates a range of values compatible with the data and the assumptions of the method; it does not guarantee that the true value lies within that interval. A p-value, when used, describes how incompatible data are with a specified null model under the analysis assumptions. Neither substitutes for a clear endpoint definition or an appropriate design.

No confidence interval, p-value, or other inferential result for the listed outcomes is reported in the registry record. The record lists zero analysis records. This does not establish what analyses may have been performed outside the registry; it means that analysis results are not available in the registry record for interpretation.

What is the role of planning illustrations?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, allocation, significance level, and statistical method. It is not an observed result and does not measure the probability that a completed study has found a true effect. The record’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. It also states that the calculations are illustrations rather than the trial’s own design.

Those assumptions describe a hypothetical two-arm planning framework, whereas this study is recorded as single-group. The record does not report the calculated planning values in the registry record for this analysis, and no efficacy effect estimate is reported. The illustration should therefore not be interpreted as an analysis of the observed trial or as observed power. The trial’s own sample-size justification is not reported in 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(251)
events <- c(184)
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  251  184  73.3  67.4  78.7  67.5  78.4  67.5  78.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and six secondary outcomes. They cover adverse events, seizure-frequency changes, response thresholds, categorized change in severity of illness, and retention. When several outcomes are assessed, multiplicity is a general statistical concern: repeated testing can increase the chance of at least one apparently notable result even when no adjustment is used. Whether an adjustment is appropriate depends on the analysis objectives and prespecified plan.

The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or numerical analyses for those outcomes. It lists zero analysis records. The registry record also does not report whether any interim analyses were planned or conducted, or give a detailed statistical analysis plan. These details should not be inferred from the outcome list.

Missing-data handling and analysis populations are not reported in the registry record. The record gives enrollment of 251 and lists 251 at risk in each safety category, but does not describe participant flow, missing assessments, withdrawals, or the number contributing to each secondary outcome. The listed safety denominators alone do not establish completeness of follow-up or explain how missing information was handled.

In general, missing outcomes can affect interpretation if participants with unavailable assessments differ from those with observed assessments. The registry does not describe imputation, exclusion rules, sensitivity analyses, or how partial follow-up was treated. The planned analysis population, including whether any analysis was intended to include all enrolled participants or only a defined subset, is not reported in the registry record.

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: convulsion (1.6%), dizziness (0.8%), grand mal convulsion (0.8%), bicytopenia (0.4%), adverse drug reaction (0.4%).

The registry lists 15 participants with serious adverse events among 251 at risk and 136 participants with other adverse events among 251 at risk. These are participant counts in the safety record. They should not be added together to infer a number of distinct participants, because the record does not state whether the categories overlap or how they were operationally defined.

The listed serious-event terms and reported percentages are Convulsion, 1.6%; Dizziness, 0.8%; Grand mal convulsion, 0.8%; Bicytopenia, 0.4%; Adverse drug reaction, 0.4%; and Dengue fever, 0.4%. The registry does not report whether these terms represent unique people, whether participants could have multiple terms, or the detailed event-level calculations behind the percentages. They should be read as registry listings, not as a complete account of event episodes.

The record defines an adverse event as an untoward medical occurrence that does not necessarily have a causal relationship with treatment. The counts therefore describe recorded events during the study, not events proven to have been caused by levetiracetam. No death count is reported in the registry record. Further details about severity criteria, seriousness criteria, timing, outcomes, or causality assessments are not reported in the registry record.

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

The results establish that the registry records adverse events among participants in an open-label, single-group study of levetiracetam. Specifically, the safety summaries list 15 participants with serious adverse events and 136 with other adverse events, each among 251 at risk. The record also identifies several serious-event terms with reported percentages. These observations describe the study group and its recorded safety experience.

They do not establish that levetiracetam caused any particular event. The registry’s adverse-event definition explicitly allows events without a causal relationship to treatment. The absence of a comparator also means the counts cannot be contrasted with what would have happened in a similar group not receiving levetiracetam or receiving another intervention. A causal interpretation would require evidence beyond these descriptive counts.

The record does not report an overall numerical result for the primary endpoint as titled, despite listing separate serious and other adverse-event counts. It does not provide confidence intervals or inferential analyses for these safety figures. The numerical results for the secondary seizure-frequency, response, illness-severity, and retention outcomes are also not reported in the registry record. Consequently, the outcome descriptions alone do not establish the magnitude or precision of any efficacy change.

In general, an observed count is not a prediction for every person or setting. It reflects the participants recorded in a particular study and the event definitions and follow-up used. Here, further information about participant characteristics, dose, completeness of follow-up, event assessment, and missing data is not reported in the registry record. Those gaps limit how far the observations can be generalized or compared with other settings.

The record therefore supports a descriptive reading of reported safety counts, with substantial limits on causal and comparative interpretation. It does not provide a randomized estimate of treatment benefit, a numerical estimate of treatment effect on seizure outcomes, or a precise comparative assessment of safety.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between the question it names and the evidence its design can provide. It describes an open-label, single-group study and names a safety count as the primary endpoint. The resulting participant counts are useful descriptions of events recorded during follow-up, but they are not comparative estimates because there is no randomized control group.

That distinction is important when readers encounter adverse-event counts. In general, an event occurring during treatment is not automatically an event caused by treatment. The registry’s definition makes this explicit, and the design does not include a concurrent group that could help estimate background event frequency under a comparable study process. The reported figures should therefore be read as observations in the enrolled group, not as a causal contrast.

The trial also illustrates why endpoint names and outcome results must be distinguished. The registry lists six secondary outcomes addressing seizure frequency, response, illness severity, and retention, but their numerical results are not reported in the registry record. A list of planned or registered outcomes communicates what investigators intended to measure; it does not show the magnitude, uncertainty, or direction of the observed findings.

Finally, registry reporting is part of the evidence available for statistical interpretation. Here, the analysis records are absent, and key details about missing data, analysis populations, and the statistical plan are not reported. These omissions limit the ability to assess precision, multiplicity, and outcome completeness. The trial remains interpretable as a record of a completed single-group study with reported safety counts, but its registry record does not support broader comparative conclusions.

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 absence of a randomized comparator is a central limitation for interpreting both safety and efficacy. The study is open-label and single-group, so it cannot directly estimate differences between levetiracetam and another treatment or a control condition. The registry also records allocation as not applicable and masking as none.

Numerical efficacy results are not reported in the registry record, despite the listing of secondary outcomes related to seizure frequency, response, illness severity, and retention. The overall numerical result for the primary endpoint as titled is also not reported; the registry instead lists separate serious and other adverse-event counts. No confidence intervals, p-values, or other inferential results are reported.

Participant characteristics beyond the condition and adult population described in the title are not reported in the registry record. The actual dose, treatment exposure details, participant flow, withdrawals, adherence, and completeness of follow-up are also not reported. The record does not describe missing-data methods, analysis populations, event adjudication, or detailed event definitions beyond its general adverse-event definition.

The serious-event term percentages are listed without further calculation details, and the registry does not explain whether terms can overlap across participants. The death count is not reported in the registry record. The sample-size justification, detailed statistical plan, and interim analyses are not reported in the registry record. These limitations leave the safety summaries descriptive and restrict assessment of precision, selection, and outcome completeness.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open Label Safety and Efficacy Study of Levetiracetam in Patients With Epilepsy — NCT00160654.
• Registry record last updated 2020-08-19; status last verified 2020-08.
• Results first posted 2020-08-19.
• 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

The registry describes a completed Phase IV, open-label, multicenter, community-based, single-group study in Asia of levetiracetam as adjunctive therapy for adults with uncontrolled partial epilepsy. Enrollment was 251. The primary endpoint was the number of participants with adverse events from baseline until the safety visit, two weeks after the last dose and up to Week 18.

The safety summaries list 15 participants with serious adverse events and 136 with other adverse events, each among 251 at risk. Serious-event terms and percentages are also recorded. Numerical results for the listed efficacy outcomes, the overall primary-endpoint count, and inferential analyses are not reported in the registry record.

With no randomized comparator, the findings are descriptive rather than comparative. The record does not report detailed analysis methods, missing-data handling, analysis populations, or the trial’s sample-size justification.