A Study to Test the Long-term Use of Oral Lacosamide in Pediatric Study Participants Who Completed NCT01964560 (EP0034) or NCT00938912 (SP848) and Received Lacosamide Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Test the Long-term Use of Oral Lacosamide in Pediatric Study Participants Who Completed NCT01964560 (EP0034) or NCT00938912 (SP848) and Received Lacosamide Treatment (NCT04627285), a na phase 3 study. The primary outcome is Percentage of Participants With Treatment Emergent Adverse Events (TEAEs).

2. Clinical Question

The study asks about long-term use of oral lacosamide among pediatric participants with epilepsy who completed EP0034 or SP848 and received lacosamide treatment. It is a follow-up study, not a randomized comparison of lacosamide with a control treatment. The primary endpoint concerns the percentage of participants with treatment-emergent adverse events during the follow-up period. The registry record also reports selected serious adverse-event counts by age group.

3. Trial Design

This is a Phase 3, multicenter, open-label, single-group follow-up study sponsored by UCB Biopharma SRL. It is listed as completed, with a start date of 2020-12-28 and a primary completion date of 2025-02-12. The registry lists enrollment of 48 participants. Its stated purpose is to assess long-term use of oral lacosamide in pediatric participants with epilepsy who completed EP0034 or SP848 and received lacosamide treatment.

There is no randomized allocation or masking. The design therefore does not create a concurrent control group for estimating what would have happened to similar participants without lacosamide or under another treatment. The age-group safety counts are descriptive and do not turn the study into a controlled comparison. Differences between age groups could reflect differences in the participants or their follow-up, and the record does not report an analysis that adjusts for such differences.

The study is described as assessing long-term use, with primary-endpoint follow-up from visit 1 at Week 0 through the end-of-study visit, up to Week 214.42. That timeframe identifies the period considered for the endpoint; it does not establish that every participant was followed for the same duration. Individual follow-up durations and their distribution are not reported in the registry record.

The intervention descriptions merit care in interpretation. The study purpose describes oral solution dosed at 2 mg/kg/day to 12 mg/kg/day, while the arm description says participants received various single doses. The registry record does not resolve this difference, so a specific dosing schedule or exposure pattern should not be inferred from these descriptions. The protocol details, eligibility criteria, dose changes, and reasons for discontinuation are not reported in the registry record.

The registry lists five outcome measures and no statistical analyses. It does not report a sample-size justification, a planned interim analysis, or a statistical analysis plan. Accordingly, the enrollment figure should not be read as proof that the study was designed to detect a specified effect or to estimate an endpoint with a particular precision.

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: Participants who completed studies EP0034 (NCT01964560) or SP848 (NCT00938912) were offered participation in this study. The Participant Flow refers to the Safety Set (SS).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The SS consisted of all study participants who signed an ICF and took at least 1 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 SS consisted of all study participants who signed an informed consent form (ICF) and took at least 1 dose of study medication in this study.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), measured over From visit 1 (Week 0) to the end of study visit (up to Week 214.42).

The primary endpoint is the percentage of participants with treatment-emergent adverse events, expressed as a percentage of participants. An adverse event is defined in the registry as an unfavorable or unintended medical occurrence temporally associated with use of a medicinal product, whether or not it is considered related to that product. Treatment-emergent events are defined as events that began on or after the first lacosamide dose in EP0151, or events whose severity worsened on or after that dose. Events occurring within 30 days after the final EP0151 lacosamide dose are also considered treatment-emergent.

The stated timeframe is from visit 1 at Week 0 to the end-of-study visit, up to Week 214.42. An endpoint of this kind is used to describe how often participants experience events under observation during treatment and follow-up. It is a safety measure, not by itself a measure of whether an event was caused by the study treatment. The definition explicitly allows events to count regardless of causal relationship.

The registry record does not report the overall number or percentage of participants meeting this primary endpoint, nor an uncertainty interval or statistical test for it. The selected serious-event counts reported by age group are not a substitute for the overall primary-endpoint result: they cover serious events and other events separately, while the primary endpoint is defined as the percentage with treatment-emergent adverse events.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods can be interpreted only to the extent described in the registry record. The study is single-group, open-label, and has no allocation. It lists no statistical analyses. A detailed statistical analysis plan, including the handling of missing observations, censoring, covariates, or repeated events, is not reported in the registry record. The general explanations below clarify how to read the types of information that appear; they do not imply that a particular unreported method was used.

What does a percentage of participants measure?

A percentage of participants with an event is a participant-level summary: it describes the proportion of the defined analysis population who meet the event definition during the stated observation period. This differs from an event rate, which would account for time under observation, and from a count of all event occurrences, which could include multiple events in one participant. The primary outcome is described as a percentage of participants, but the overall result is not reported in the registry record.

For safety summaries, interpretation depends on who is included in the denominator and what qualifies as an event. The primary endpoint population is described as the safety population: participants who signed an informed consent form and took at least one dose of study medication in this study. The endpoint definition additionally specifies treatment emergence relative to the first dose in EP0151 and includes events within 30 days after the final dose. The record does not provide the overall number of participants included in the primary endpoint result, because that result is not reported.

Why does the event definition matter?

“Treatment-emergent” describes timing under a prespecified definition; it does not mean that treatment caused the event. The registry definition includes events starting after the specified dose or worsening after that dose, and it includes events within the stated period after the final dose. An adverse event can be considered in the endpoint even when there is no causal relationship to the medicinal product. A reader should therefore distinguish an event occurring during the treatment-emergent window from an event assessed as treatment-related. A treatment-related analysis is not reported in the registry record.

How should counts and percentages be read?

A raw count gives the number of participants reported as affected in a group, while the at-risk count indicates the population denominator recorded for that measure. The age-stratified entries present both counts. They do not provide uncertainty intervals or adjusted comparisons. A confidence interval, in general, expresses the statistical uncertainty around an estimate under a specified model and assumptions. Without an interval or the underlying analysis, the precision of the group-specific estimates cannot be assessed from the record.

Counts of adverse-event terms may not represent separate participants. One participant can experience more than one type of event, and the registry does not clarify whether the listed terms overlap. Consequently, term-specific percentages should not be added together or interpreted as a combined participant percentage. No such combined calculation is reported.

What can a single-group design estimate?

In general, a single-group study can describe observations among participants who receive the study intervention, subject to its population definition and follow-up. It does not provide the concurrent counterfactual comparison needed to determine how the same outcomes would have differed under another treatment or no treatment. Background disease, other care, participant selection, and time can all be relevant to observed events, but their contributions cannot be separated by a single-group comparison alone. Here, the registry explicitly cautions that the arms are not a like-for-like control comparison.

Open-label means masking is absent, as recorded for this study. In general, knowledge of treatment can influence reporting or assessment, depending on the outcome and procedures. The registry record does not describe event adjudication or other procedures that would allow a more detailed assessment of this issue. No claim about the direction or size of any such influence can be made from the posted information.

What do planning calculations mean?

Sample-size calculations are planning illustrations, not observed outcomes. In general, their assumptions specify a target effect, significance level, allocation, and statistical approximation. The planning assumptions stated for calculations associated with this record include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. Such assumptions do not describe the actual design of this single-group study, and the record cautions that the arms are not a like-for-like control comparison.

A calculation based on an observed effect does not establish that the original study was designed around that effect. Nor does a planning illustration show the probability that the completed study detected a true effect. That latter concept is sometimes called observed power, but it is not an appropriate replacement for reporting the estimate and its uncertainty. No primary-endpoint effect estimate or analysis is reported in the registry record, so the stated planning assumptions cannot be used to infer an unreported treatment effect.

Why do analysis populations matter?

An analysis population defines which participants contribute to an estimate. The record describes the safety population as participants who signed an informed consent form and took at least one dose in this study. It does not report an overall primary-endpoint estimate or provide separate population definitions for each listed outcome. The enrollment figure alone should not be assumed to equal the number contributing to every outcome: participants may have different amounts of follow-up, and endpoint-specific availability is not reported. The record also does not explain how missing visits or incomplete event information were handled.

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("Lacosamide: >=2 to <4 Years", "Lacosamide: >=4 to <6 Years")
n      <- c(19, 29)
events <- c(8, 11)
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  Lacosamide: >=2 to <4 Years  19  8  42.1  20.3  66.5  23.1  63.7  23.1  63.9
ARM  Lacosamide: >=4 to <6 Years  29  11  37.9  20.7  57.7  22.7  56.0  22.7  56.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures and no statistical analyses. It does not report a statistical analysis plan describing a primary testing hierarchy, adjustment for multiple comparisons, or a strategy for choosing which outcomes to emphasize. Multiplicity refers, in general, to the increased chance of a false-positive finding when many statistical hypotheses are tested without accounting for the number of tests. Since no statistical tests are reported, there is no reported multiplicity adjustment to interpret; it would be inappropriate to infer either that testing was adjusted or that a particular adjustment was required and omitted.

Missing-data procedures are not reported in the registry record. The endpoint timeframe extends from visit 1 at Week 0 to the end-of-study visit, up to Week 214.42, but this does not establish that all participants had complete follow-up throughout that period. The record does not describe how participants who discontinued, missed visits, or had incomplete adverse-event information were handled in endpoint summaries. It also does not report a missingness analysis or sensitivity analysis.

The safety population is described as participants who signed an informed consent form and took at least one dose of study medication in this study. That definition clarifies who is eligible for the safety population, but it does not specify the analysis population or data-handling rules for every outcome. The enrollment of 48 should not be treated as the denominator for every reported measure without an explicit endpoint-specific denominator.

In general, missing information can affect interpretation when participants with incomplete follow-up differ from those with complete follow-up. The direction and size of any such effect cannot be established without details about missingness and the analysis approach. These details, along with any imputation or censoring rules, are not reported in the registry record.

12. Safety Results

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

Deaths

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: bronchopneumonia (5.3%), pneumonia (5.3%), septic shock (5.3%), epilepsy (5.3%), cardiac failure acute (3.4%).

The serious adverse-event figures are reported by age group, with an at-risk count and an affected count for serious events and for other events. Among participants aged 2 to under 4 years, 19 were at risk and 2 were affected for serious events; the other-event figures are 19 at risk and 5 affected. Among participants aged 4 to under 6 years, 29 were at risk and 5 were affected for serious events; the other-event figures are 29 at risk and 4 affected. The recorded deaths are 0 in the younger group and 2 in the older group.

These counts describe the registry entries; they do not identify causes of events or establish a causal relationship to lacosamide. The record does not report group-specific follow-up duration, timing of individual events, or uncertainty intervals. It is therefore not possible to use the counts alone to make a fair comparison of event risk between age groups. The age categories are descriptive strata, not randomized treatment groups.

The listed serious-event terms have posted percentages: bronchopneumonia, 5.3%; pneumonia, 5.3%; septic shock, 5.3%; epilepsy, 5.3%; cardiac failure acute, 3.4%; and developmental hip dysplasia, 3.4%. The record does not state whether these terms occurred in overlapping participants or give term-specific counts. They should not be combined into a single percentage or treated as an exhaustive list of serious events.

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

The results have a narrow, descriptive meaning. This completed study followed pediatric participants with epilepsy who had completed EP0034 or SP848 and received lacosamide treatment. The registry identifies treatment-emergent adverse events as the primary endpoint and reports selected serious-event counts by age group. It does not report the overall percentage meeting the primary endpoint, an estimate of uncertainty, or a statistical analysis of that endpoint.

The record does not establish that any event was caused by lacosamide. Its adverse-event definition explicitly includes events regardless of causal relationship. The single-group design also lacks a concurrent control group, so the observed event counts cannot be compared with what would have occurred in a similar group under a different treatment or no study treatment. No causal treatment effect can be estimated from the posted counts alone.

The reported age-stratified counts do not show whether groups differ in underlying risk. The registry does not provide group-specific follow-up duration, adjusted comparisons, or uncertainty intervals. Nor does it explain whether the listed serious-event terms overlap within participants. The term-specific percentages describe the posted entries, not an overall percentage of participants with any serious event.

The study’s long-term follow-up purpose and the stated endpoint window describe what was intended to be observed, not the duration experienced by each participant. The registry record does not report individual follow-up or completeness. Its dosing descriptions are also not fully aligned: the study purpose describes oral solution dosed at 2 mg/kg/day to 12 mg/kg/day, while the arm description says various single doses. The record does not resolve that ambiguity.

Accordingly, the posted information can describe selected safety observations but cannot support a treatment-versus-control conclusion, an estimate of the overall primary endpoint, or a claim about the frequency of all events across the full study population. Those outcomes are not reported in the registry record.

14. Why This Trial Matters Statistically

Long-term follow-up studies address a different statistical question from controlled trials focused on a treatment comparison. They can collect observations over an extended period among participants who have previously received treatment, and can describe events recorded during that follow-up. That descriptive role is relevant when the primary interest is ongoing observation in a defined participant group. In this study, the registry identifies a treatment-emergent adverse-event endpoint and a follow-up period extending from Week 0 to an end-of-study visit up to Week 214.42.

The design also illustrates why a clearly defined estimand and analysis population matter. A participant-level percentage depends on which participants qualify, what counts as an event, and what follow-up window applies. Here, the record defines treatment emergence and describes the safety population, but does not report the overall primary-endpoint result or its precision. Readers can identify the intended measure while recognizing that the estimate itself is unavailable in the registry record.

The study also demonstrates the interpretive limits of descriptive safety data. Age-specific counts and serious-event terms can provide information about what was recorded, but without a concurrent comparator they do not estimate a causal treatment effect. Without follow-up duration, uncertainty intervals, and information about overlap among event terms, the counts cannot answer every question about comparative risk or precision.

Finally, the inconsistent dosing descriptions and unreported statistical analysis details are important record-level context. They mark the boundary between what can be stated directly and what would require protocol or analysis documentation. Statistically, a careful account distinguishes an observed event during follow-up from causation, a raw count from a comparative estimate, and a planning calculation from the completed study’s results.

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 interpreting this record is that it does not report the overall primary-endpoint result. Although the endpoint is defined as the percentage of participants with treatment-emergent adverse events and its timeframe is stated, the corresponding overall count or percentage and its statistical uncertainty are not reported in the registry record. The registry lists five outcome measures but no statistical analyses.

The single-group, open-label design has no concurrent control group and no allocation. It therefore cannot establish a comparative treatment effect. The record itself warns that the arms are not a like-for-like control comparison. Any events observed may be temporally associated with treatment under the endpoint definition without being caused by treatment.

The record does not report individual or age-group follow-up duration, event timing, endpoint-specific missingness, or how incomplete follow-up was handled. This limits interpretation of the age-stratified counts. It also does not provide uncertainty intervals or adjusted analyses, so the precision of those descriptive figures and any differences between age groups cannot be assessed from the posted information.

The serious-event term percentages are not accompanied by term-specific counts or an explanation of whether terms overlap among participants. The listed terms therefore cannot be treated as mutually exclusive or added into a combined figure. The record also does not report detailed event adjudication procedures or a treatment-related analysis.

Finally, the study purpose describes oral solution at 2 mg/kg/day to 12 mg/kg/day, whereas the arm description says various single doses. The record does not reconcile those statements or provide a full dosing schedule. Protocol details, eligibility criteria, sample-size justification, interim analyses, and the statistical analysis plan are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Test the Long-term Use of Oral Lacosamide in Pediatric Study Participants Who Completed NCT01964560 (EP0034) or NCT00938912 (SP848) and Received Lacosamide Treatment — NCT04627285.
• Registry record last updated 2025-08-28; status last verified 2025-08.
• Results first posted 2025-08-28.
• 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

NCT04627285 is a completed, Phase 3, multicenter, open-label, single-group follow-up study sponsored by UCB Biopharma SRL. It enrolled 48 pediatric participants with epilepsy who had completed EP0034 or SP848 and received lacosamide treatment. The study purpose describes long-term oral lacosamide use; the record gives a dose range of 2 mg/kg/day to 12 mg/kg/day, while its arm description refers to various single doses.

The primary endpoint is the percentage of participants with treatment-emergent adverse events from visit 1 at Week 0 through the end-of-study visit, up to Week 214.42. The registry reports selected serious-event counts by age group and term-specific percentages, but not the overall primary-endpoint result or statistical analyses. With no concurrent control group, the reported safety figures are descriptive and do not establish causation or a comparative treatment effect.