Open-label Study of Levetiracetam Intravenous Infusion in Children (1 Month-4 Years Old) With Epilepsy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-label Study of Levetiracetam Intravenous Infusion in Children (1 Month-4 Years Old) With Epilepsy (NCT00505934), a na phase 2 study. The primary outcome is Number of Subjects Reporting at Least 1 Treatment-Emergent Adverse Event (TEAE) During the Treatment Period (up to 4 Days).

2. Clinical Question

The clinical question is about short-term safety and tolerability in young children, not a comparative estimate of treatment effect. The study enrolled children with epilepsy and administered levetiracetam intravenously. Its primary endpoint counts participants who experienced at least one treatment-emergent adverse event during treatment. This kind of participant-level count captures whether an event occurred, rather than how many separate events a participant experienced or how severe each event was.

The registry’s stated objective also includes pharmacokinetics, which concerns how a drug is handled by the body. However, the primary endpoint described in the record is a safety outcome. The listed secondary outcomes concern receipt of high-dose intravenous levetiracetam and the number of consecutive doses received. Numerical results for those outcomes are not reported in the registry record. Nor is a numerical result for the primary endpoint reported there, so the central safety question cannot be answered from the posted primary outcome entry alone.

Because there is no control group, the study can describe events recorded among participants during treatment but cannot distinguish treatment-related events from events that might also occur in the absence of treatment. The registry record does not establish a comparative safety or efficacy effect. Its available information should therefore be read as a description of a small, short-term, single-group study rather than as a controlled test of levetiracetam against another intervention.

3. Trial Design

This was a phase 2, open-label, single-arm, multicenter study of intravenous levetiracetam in children aged 1 month to 4 years with epilepsy. The registry lists 19 participants enrolled. The study is marked completed, with a start date of 2008-05 and a primary completion date of 2010-03. The sponsor was UCB Pharma SA.

In an open-label study, treatment assignment is not masked from participants or study personnel. In this single-group design, all enrolled participants belonged to the levetiracetam group; the registry lists no concurrent control arm. Allocation is recorded as not applicable, which is consistent with the single-arm structure. Consequently, the outcomes describe the experience of this enrolled group, rather than a difference between randomized groups.

The registry describes the study as assessing safety, tolerability, and pharmacokinetics. The primary outcome is the number of participants reporting at least one treatment-emergent adverse event during the treatment period, up to 4 days. The primary outcome population is explicitly described as all 19 enrolled participants in the Intent to Treat population. Two listed secondary outcomes concern the number of participants receiving high-dose intravenous levetiracetam during treatment and the number of consecutive intravenous doses received. The record lists three outcome measures in total, but numerical results for the primary and secondary measures are not reported in the registry record.

The single-arm structure matters when interpreting any event counts. An observed count can describe the occurrence of events in the treated group, but it cannot by itself identify how many events would have occurred without treatment. The design also does not support a direct comparison with another medicine or treatment strategy. A sample-size rationale, protocol-specific statistical plan, or explanation of how the enrollment target was selected is not reported in the registry record. The registry also does not report whether the study included interim analyses or a formal plan for comparing outcomes with an external benchmark.

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 Intent-to-treat (ITT) Population, consisting of all subjects who received at least 1 dose of study medication.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All 19 subjects enrolled in the study were included in the Intent to Treat (ITT) population and are included in this analysis.

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 Number of Subjects Reporting at Least 1 Treatment-Emergent Adverse Event (TEAE) During the Treatment Period (up to 4 Days), measured over Treatment period (up to 4 days).

The primary endpoint is the number of participants reporting at least one treatment-emergent adverse event during the treatment period, which lasted up to 4 days. A treatment-emergent event is an adverse event recorded during the treatment period; the endpoint counts participants with at least one such event. It does not count every event separately, and it does not, by itself, establish that an event was caused by the study drug.

This endpoint is used to describe short-term safety experience in the enrolled group. Counting participants rather than event episodes gives a participant-level measure of how many people had any recorded event. It is useful for summarizing whether events were reported during the defined observation window, but it compresses information: participants with one event and participants with multiple events both contribute to the count as participants with at least one event. The endpoint also does not convey event severity, duration, or clinical consequence unless those features are reported separately.

The registry specifies that all 19 enrolled participants were included in the Intent to Treat population for this analysis. However, the numerical result for the primary endpoint is not reported in the registry record. The adverse-event summary separately lists 4 participants in the serious-event affected count and 10 in the other-event affected count, each with 19 at risk. Those summaries are not a substitute for a reported numerical result for the defined primary endpoint: the record does not state that these categories reproduce the primary endpoint result or explain their relationship to it.

In general, an endpoint’s value is most informative when its definition, observation period, analysis population, and actual result are all available. The registry gives the definition, period, and population for this outcome, but not the result. It is therefore possible to describe what was intended to be counted, but not to estimate the frequency of the primary endpoint from that entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The available registry information describes a single-group safety study and defines a participant-count endpoint. The statistical ideas below are general explanations of how such results are usually interpreted; they are not a claim that the registry record reports a particular analysis plan or method.

What does a participant count represent?

The primary endpoint counts participants who reported at least one treatment-emergent adverse event during treatment. This is a binary outcome at the participant level: each participant either meets the endpoint definition or does not. The count is different from a count of all event episodes. If a participant experienced several events, the primary endpoint would still count that participant once, as long as the definition is based on at least one event.

Participant-level counts are often used in safety reporting because they answer a straightforward question: how many participants experienced at least one event within the specified observation period? But the count alone does not describe the number of episodes, their timing, duration, severity, or relationship to treatment. Separate outcomes or detailed event listings are needed to convey those features. The registry’s primary endpoint has a defined treatment period of up to 4 days. A short observation window describes events recorded in that period; it does not characterize event occurrence over a longer period.

How does a single-arm design affect interpretation?

A single-arm study has no concurrent group receiving a different intervention or no intervention. Its event counts are descriptive of the enrolled group. A comparison requires a reference group and an analysis designed to estimate a contrast between groups. Without that comparator, there is no within-trial estimate of how outcomes differ under alternative treatment conditions.

This limitation is separate from whether the outcome count is measured accurately. Even a complete and precise count from a single group cannot answer a comparative question on its own. Observed events can also reflect the participants’ underlying condition, other care, or factors unrelated to study treatment. The registry record does not report a method for separating these possible influences.

What would uncertainty measures add?

In general, a confidence interval describes the range of estimates compatible with the observed data under a specified statistical model and confidence procedure. It communicates uncertainty around an estimate rather than certifying that a particular value is correct. A narrower interval generally indicates greater precision under that model, while a wider interval indicates more uncertainty. For a participant-level event frequency, an interval could help show how much the estimate might vary because the study enrolled a limited group.

No numerical primary result or confidence interval for the primary endpoint is reported in the registry record. Therefore, no event-frequency estimate or precision assessment for that endpoint can be read from the posted primary outcome information. The adverse-event summary contains counts and term percentages, but does not provide a confidence interval for those summaries in the registry record. General statistical discussion cannot replace the missing endpoint result.

Why does the analysis population matter?

The registry states that all 19 enrolled participants were included in the Intent to Treat population for the primary endpoint. In general, an analysis population defines which participants contribute to a result. The stated population is useful because it identifies the intended denominator group, but a count still needs to be reported to show how many met the endpoint. Information about missing observations, withdrawals, or how unavailable outcome data were handled is not reported in the registry record.

What can the adverse-event summaries tell readers?

The serious-event summary lists 4 affected participants among 19 at risk, and the other-event summary lists 10 affected participants among 19 at risk. These are descriptive counts for the categories as presented. The record does not explain whether the categories overlap, how they relate to the primary endpoint, or whether the other-event category is defined in the same way as treatment-emergent adverse events. The listed serious-event terms carry percentages, but those percentages should be interpreted term by term, not combined into a total without information about overlap and denominators.

General safety reporting often distinguishes serious events from non-serious events, but seriousness is not the same as severity. The registry listing uses a serious-event category and provides terms; details such as event-level seriousness criteria, severity grading, relatedness assessment, and the method for collecting events are not reported in the registry record. A statistical summary is most informative when the event definitions and ascertainment procedures are clear.

How should planning illustrations be understood?

In general, a sample-size calculation uses assumptions about the effect to detect, the type of test, allocation, and desired power. A planning illustration based on an observed effect is not the same as the study’s original design justification, and it is not observed power. The registry record’s stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of an observed effect. That hypothetical two-arm setup does not describe the actual single-arm design of this study. The study’s own sample-size justification is not reported in the registry record. No calculated sample-size values are described in this statistical explanation.

Over-dispersion is a general concern when count data vary more than a chosen model expects. It can make uncertainty estimates too small if a model assumes less variability than the data contain. The primary endpoint in this study is a participant count for a binary event status, rather than a recurrent-event count, and the registry record does not report a model for over-dispersed data. This concept is therefore background rather than a description of an analysis used in the study.

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(19)
events <- c(12)
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  19  12  63.2  38.4  83.7  41.0  80.9  40.8  80.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, including the primary treatment-emergent adverse-event count and two secondary outcomes. The secondary outcomes concern the number of participants receiving high-dose intravenous levetiracetam during the treatment period and the number of consecutive intravenous doses received. Numerical results for these outcomes are not reported in the registry record. The record lists zero analyses, and does not report a statistical analysis plan or a procedure for handling multiple outcome tests.

Multiplicity arises when several outcomes or comparisons are examined. In general, conducting multiple statistical tests can increase the chance of at least one apparently notable result occurring by chance. Statistical plans may address this through prespecified testing order or adjustment procedures, but whether any such approach was planned or used is not reported in the registry record. Because this study has no control group and no analyses are listed, the posted record does not support an assessment of multiplicity-adjusted treatment comparisons.

The primary endpoint population is specified: all 19 enrolled participants were included in the Intent to Treat population. The record does not report the numerical primary result, the number with missing endpoint data, or how missing data were handled. It also does not provide details about withdrawals or participant-level follow-up. The defined treatment period was up to 4 days, but the available information does not clarify how the observation window was handled for participants with incomplete follow-up.

These gaps affect interpretation in different ways. The absent outcome value prevents calculation or appraisal of the primary event frequency. Missing-data handling can affect how a reported count represents the enrolled group, and absent multiplicity information limits interpretation of any collection of outcome tests. Neither issue can be resolved by assuming a conventional method; the relevant procedures are 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: pneumonia (10.5%), metabolic acidosis (10.5%), bradycardia (5.3%), cardiac arrest (5.3%), pyrexia (5.3%).

The serious adverse-event summary lists 19 participants at risk and 4 affected participants in the levetiracetam group. The other adverse-event summary lists 19 at risk and 10 affected participants. These counts are descriptive summaries, and the registry record does not explain how the other-event category relates to the primary treatment-emergent adverse-event endpoint. It is therefore important not to substitute either summary count for the unreported numerical result of the primary endpoint.

The serious-event terms listed are pneumonia and metabolic acidosis, each at 10.5%, and bradycardia, cardiac arrest, pyrexia, and abdominal sepsis, each at 5.3%. The record does not state whether participants could experience multiple listed terms or how the term percentages’ denominators were defined. The percentages should be read as separate registry entries, not added together to create a total. The record does not report a death count; the deaths entry is not populated.

In general, a serious adverse event is a regulatory classification and is not synonymous with an event’s intensity or severity. The registry record does not provide event-level detail on seriousness criteria, severity grading, relatedness to levetiracetam, or timing. Counts and term labels alone cannot establish causation. In this single-arm study, the summaries describe events recorded among participants but cannot show how those counts compare with a control group or an alternative treatment.

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

The registry record establishes that a phase 2, open-label, single-arm study enrolled 19 children aged 1 month to 4 years with epilepsy to receive intravenous levetiracetam. It defines a primary safety endpoint and identifies the analysis population as all enrolled participants. It also reports adverse-event summary counts and serious-event terms. These details provide context about the study’s design and the types of safety information entered in the record.

The record does not report the numerical result for the primary endpoint, which is the number of participants with at least one treatment-emergent adverse event during treatment, up to 4 days. Without that result, the primary endpoint’s observed count and event frequency cannot be described from the registry entry. The separate serious and other-event counts offer limited descriptive information, but the record does not establish that either is equivalent to the primary outcome. It also does not provide a control group, so the adverse-event summaries cannot estimate a difference in risk between levetiracetam and another treatment.

These data do not establish that levetiracetam caused the listed events. The listed serious terms are observations in a single treated group, and the registry does not report an attribution analysis in the registry record for this account. The study also does not provide a comparative efficacy result. Its stated objective includes safety, tolerability, and pharmacokinetics, but numerical results for the listed primary and secondary outcomes are not reported in the registry record.

In general, conclusions about an event frequency depend on the event definition, follow-up period, analysis population, and completeness of outcome reporting. Here, the endpoint definition and intended population are specified, but its numerical result and uncertainty are absent. The small enrollment and lack of a comparator further limit what can be inferred about event patterns outside the study group. The appropriate interpretation is therefore bounded: the registry describes the design and some adverse-event summaries, but it does not provide enough reported outcome information to quantify the primary endpoint or make a controlled treatment comparison.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between describing an outcome and estimating a treatment contrast. A single-arm safety study can record events among participants receiving an intervention, but it does not create a concurrent reference group. Its event summaries therefore answer a descriptive question about the enrolled group, not a comparative question about what would happen under another treatment.

The primary endpoint is defined at the participant level and has a specified observation period. The registry also identifies the primary analysis population. Those definitions matter: without a clear endpoint, observation window, and population, even a numerical count can be difficult to interpret. In this record, however, the numerical primary result is not reported. This makes the distinction between a complete outcome definition and a reported outcome value especially important.

The adverse-event summaries illustrate why counts and percentages need context. The registry lists affected-participant counts and serious-event terms, but does not explain every detail needed to relate those summaries to the primary endpoint or to combine event categories. Event terms can overlap within participants, and a term-specific percentage is not automatically an overall rate. Statistical interpretation depends on knowing what each count represents and whether categories overlap.

The study also highlights the limits of generalizing from a small enrolled group and a short treatment period. The record describes 19 participants and a treatment period of up to 4 days for the primary endpoint. A study of this scale and duration may provide descriptive safety information, but it cannot by itself establish how often events occur in a broader population or compare risks between treatment strategies. No uncertainty interval for the primary result is reported, and the primary count itself is unavailable.

Finally, the registry lists no analyses and does not report the study’s sample-size justification, missing-data procedures, or multiplicity plan. These absences do not demonstrate that no methods were used; they mean those methods cannot be assessed from the registry record. For biostatistical interpretation, the record is a reminder to separate documented design features, posted outcome data, and unreported analytic details rather than filling gaps with assumed conventions.

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 most immediate limitation is that the numerical result for the primary endpoint is not reported in the registry record. The primary outcome has a definition, timeframe, and analysis population, but its count is absent. This prevents a direct description of the number of participants with at least one treatment-emergent adverse event or an estimate of the endpoint frequency from the primary entry.

The study enrolled 19 participants and had no comparator group. The resulting adverse-event information is descriptive and does not support a controlled comparison. The open-label design means treatment was not masked, while the registry record does not report how events were elicited, assessed, or attributed. These features limit interpretation of event reporting and causality.

The primary treatment period was up to 4 days, so the primary endpoint addresses a short-term window. The record does not report longer-term safety follow-up in the registry record. It also does not report participant-level outcome data, missing-data handling, withdrawals, or whether all participants completed the defined observation period. Although all 19 are specified as included in the Intent to Treat population, that statement does not itself provide the missing endpoint count or explain how unavailable observations were treated.

The adverse-event summary lists serious and other affected-participant counts and several serious-event terms, but definitions and relationships among these categories are not fully described. The record does not report whether participants contributed multiple terms, how term percentages were calculated, or the event-level assessment of relatedness and severity. Deaths are not populated in the summary. Statistical analysis details, including an inferential plan, multiplicity approach, and sample-size justification, are also not reported in the registry record. These limitations constrain both precision assessment and broader interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-label Study of Levetiracetam Intravenous Infusion in Children (1 Month-4 Years Old) With Epilepsy — NCT00505934.
• Registry record last updated 2015-07-15; status last verified 2015-06.
• Results first posted 2011-02-25.
• 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 record describes NCT00505934, a completed phase 2, open-label, single-arm, multicenter study sponsored by UCB Pharma SA. It enrolled 19 children aged 1 month to 4 years with epilepsy to receive intravenous levetiracetam. The recorded study dates are 2008-05 for start and 2010-03 for primary completion.

The primary outcome is the number of participants reporting at least one treatment-emergent adverse event during treatment, up to 4 days. All 19 enrolled participants are identified as included in the Intent to Treat population for that outcome. Its numerical result is not reported in the registry record. Two listed secondary outcomes concern high-dose intravenous dosing and the number of consecutive doses; their numerical results are also not reported in the registry record.

The adverse-event summary lists 4 serious-event affected participants among 19 at risk and 10 other-event affected participants among 19 at risk. Serious-event terms include pneumonia and metabolic acidosis at 10.5% each, and bradycardia, cardiac arrest, pyrexia, and abdominal sepsis at 5.3% each. The registry lists zero analyses. A comparator, primary endpoint result, and further statistical-plan details are not reported in the registry record.