This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Post-Authorization Safety Study to Assess the Safety of Vimpat as add-on Therapy in Patients With Partial-onset Seizures (NCT00771927), a registered phase not stated study. The primary outcome is The Incidence of Predefined Cardiovascular Treatment-Emergent Adverse Events (TEAEs) in Epilepsy Patients With Partial-onset Seizures While on Vimpat or Any Other add-on Antiepileptic Drug (AED) Treatment During the Study.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00771927 |
| Phase | Phase not stated |
| Condition | Epilepsies, Partial |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 1005 |
| Arms in the primary outcome | n/a |
| Lead sponsor | UCB Pharma |
| Results posted | Yes |
2. Clinical Question
Population
Epilepsy patients aged 16 years and older with partial-onset seizures who were uncontrolled on their current therapy. The primary outcome population is the Safety Set. The registry record reports enrollment of 1005, but does not give a single combined analysis count for the outcome groups.
Intervention
Add-on Vimpat, whose active ingredient is lacosamide. The study describes long-term safety and tolerability during clinical use rather than assignment to treatment by a trial protocol.
Comparator
Other approved antiepileptic drugs used as add-on therapy in patients with partial-onset seizures uncontrolled on current therapy. Allocation is not stated, and the arms are not a like-for-like control comparison.
Primary question
What number of predefined cardiovascular treatment-emergent adverse events was reported during the period from baseline up to 12 months among patients receiving add-on lacosamide or another add-on antiepileptic drug?
The predefined cardiovascular events were atrioventricular block, syncope, bradycardia, and PR prolongation, identified through specified MedDRA Preferred Terms. A treatment-emergent event began on or after the first intake of the add-on treatment and could be counted through 30 days after the last intake.
A secondary outcome concerned predefined psychiatric treatment-emergent adverse events. Although the registry lists both outcome areas, it does not report analyses for either. The clinical question is therefore about what the study set out to monitor; the record does not provide an analyzed cardiovascular or psychiatric comparison from which to estimate how often these outcomes occurred in either group.
3. Trial Design
This is a completed, non-interventional post-authorization safety study. The registry identifies UCB Pharma as sponsor and describes the study as an assessment of long-term safety and tolerability of Vimpat, or lacosamide, when used as add-on therapy. The study began in 2008-10, and primary completion was recorded in 2012-03. The registry reports enrollment of 1005.
The population was epilepsy patients aged 16 years and older with partial-onset seizures who were uncontrolled on current therapy. One group was treated with add-on lacosamide; the other was treated with another approved antiepileptic drug as add-on therapy. The registry does not state how treatment was allocated. This is not a randomized comparison, and the arms are not a like-for-like control comparison. Differences between the groups could reflect who received each treatment and the circumstances of routine care, as well as any differences in reported events.
The primary outcome was the number of predefined cardiovascular treatment-emergent adverse events from baseline up to 12 months. The registry also lists predefined psychiatric treatment-emergent adverse events as a secondary outcome. The primary outcome population is identified as the Safety Set. The record does not describe additional eligibility details, follow-up procedures, or the statistical analysis plan.
The registry lists zero analyses. That means the record does not display an analyzed result for the primary outcome or the secondary outcome; it does not establish whether analyses were conducted outside the registry record. The posted safety summaries give adverse-event counts for the treatment groups, but these summaries do not supply the missing outcome-specific cardiovascular or psychiatric analyses.
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: Patient procedures and assessments were performed in the frame of the current standard practice at the discretion of the treating physician. Each patient was followed for the initial 12 months of add-on AED treatment. A Safety Follow-Up Visit is recommended for any patient who terminates add-on AED treatment before the end of the study period.
Overall Study
| Stage | Lacosamide | Other AED |
|---|---|---|
| STARTED | 511 | 493 |
| COMPLETED | 256 | 256 |
| NOT COMPLETED | 255 | 237 |
Reasons for not completing this period:
| Reason | Lacosamide | Other AED |
|---|---|---|
| Adverse Event | 100 | 105 |
| Lack of Efficacy | 70 | 42 |
| Lost to Follow-up | 46 | 46 |
| Withdrawal by Subject | 16 | 17 |
| Other reason | 23 | 27 |
Analysis population for the primary outcome, as defined in the registry: Safety Set (SS) population
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 Safety Set (SS). Safety Set includes all patients who have signed a data consent form, provided Baseline characteristic data, and received treatment at least once.
| Characteristic | Unit | Lacosamide | Other AED | Total |
|---|---|---|---|---|
| Participants analysed | 511 | 493 | 1004 | |
| Age, Categorical: <=18 years | Participants | 20 | 14 | 34 |
| Age, Categorical: Between 18 and 65 years | Participants | 467 | 434 | 901 |
| Age, Categorical: >=65 years | Participants | 24 | 45 | 69 |
| Age, Continuous | years | 39.8 (SD 13.58) | 42.3 (SD 15.38) | 41.0 (SD 14.54) |
| Sex: Female, Male: Female | Participants | 266 | 282 | 548 |
| Sex: Female, Male: Male | Participants | 245 | 211 | 456 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Asian | Participants | 5 | 4 | 9 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 481 | 464 | 945 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 24 | 22 | 46 |
| Weight | kilogram | 75.5 (SD 18.10) | 75.7 (SD 17.68) | 75.6 (SD 17.89) |
| Height | centimeter | 170.4 (SD 10.97) | 169.5 (SD 9.24) | 170.0 (SD 10.18) |
| Body Mass Index (BMI) | kilogram per square meter | 26.0 (SD 5.89) | 26.2 (SD 5.25) | 26.1 (SD 5.59) |
6. Primary Endpoint
The registry lists the primary outcome as The Incidence of Predefined Cardiovascular Treatment-Emergent Adverse Events (TEAEs) in Epilepsy Patients With Partial-onset Seizures While on Vimpat or Any Other add-on Antiepileptic Drug (AED) Treatment During the Study, measured over From Baseline up to 12 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Treatment-Emergent Adverse Events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of predefined cardiovascular treatment-emergent adverse events during the period from baseline up to 12 months. The event set includes atrioventricular block, syncope, bradycardia, and PR prolongation, identified using specified MedDRA Preferred Terms. The registry defines treatment-emergent events as those beginning on or after the first intake of add-on treatment and through 30 days after the last intake.
Monitoring a predefined event set is a way to focus safety surveillance on events of particular interest in a post-authorization study. The endpoint is recorded as a number of events, rather than a rate or a statistical contrast. The registry record does not explain whether repeated events in one participant were counted separately or how any event totals were summarized across participants. It also does not report the cardiovascular endpoint results by treatment group.
The registry lists the Safety Set as the outcome population. This identifies the population intended for the primary safety assessment, but the record does not define its membership or explain how participants with incomplete follow-up were handled. As a result, the outcome description clarifies what was to be monitored, but not how completely the endpoint was observed or how precisely any group-specific result was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a safety question, a defined cardiovascular event set, and a follow-up window, but it does not report the primary endpoint results. It lists zero analyses. There is therefore no posted estimate of the number of cardiovascular treatment-emergent adverse events in either group, and no reported comparison between add-on lacosamide and other add-on antiepileptic drugs for this endpoint. The same limitation applies to the listed psychiatric secondary outcome: its results are not reported in the registry record.
The adverse-event summaries are not substitutes for the missing endpoint analysis. They list serious and other adverse-event counts by group, but do not identify those counts as the predefined cardiovascular endpoint. In the lacosamide group, the serious adverse-event summary reports 78 affected among 511 at risk, and the other adverse-event summary reports 359 affected among 511 at risk. In the Other AED group, the corresponding figures are 64 among 493 at risk for serious adverse events and 299 among 493 at risk for other adverse events. These are descriptive safety summaries; they do not establish a treatment effect or an adjusted comparison.
The record also lists serious-event terms and percentages, including convulsion at 3.4%, grand mal convulsion at 2.2%, epilepsy at 1.4%, partial seizures at 1.0%, headache at 0.8%, and dizziness at 0.8%. Those terms describe the listed serious-event profile; they should not be read as results for the predefined cardiovascular endpoint. The record does not specify the denominator or further calculation details for these listed percentages.
Because allocation is not stated and the study is non-interventional, treatment groups may differ in ways that influence both treatment choice and adverse-event reporting. The registry explicitly cautions that the arms are not a like-for-like control comparison. No confidence intervals, hypothesis tests, adjusted estimates, or analysis methods are reported. Consequently, the posted summaries do not quantify statistical uncertainty around a cardiovascular comparison, and they do not support a causal interpretation of differences in the general adverse-event counts.
The study is recorded as completed, but completion does not mean that all planned results are available in the registry. The defensible reading is limited to the study's stated safety objectives and the descriptive adverse-event figures that are actually reported. The cardiovascular and psychiatric outcome findings, and the statistical precision of any comparison for those endpoints, are not reported in the registry record.
9. Statistical Methods Explained
The registry describes a non-interventional safety study rather than a randomized trial. In a randomized comparison, treatment allocation is determined by a study process designed to make groups comparable in expectation. Here, allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. In general, an observed difference between non-randomized groups can reflect treatment, differences in the patients receiving treatment, differences in follow-up, or a combination of these factors. The record does not report adjustment methods that would address such differences.
What does a count endpoint represent?
The primary endpoint is expressed as the number of predefined cardiovascular treatment-emergent adverse events. A count records how many events are identified under the endpoint definition. It is not automatically the same as the number of participants who experienced an event: a participant could, in principle, experience more than one event. The registry does not explain whether repeated events were counted separately, nor does it report an event rate or a group-specific endpoint count. It is therefore important not to infer participant-level risk from the endpoint label alone.
For context, general methods for count outcomes can differ depending on how the data are collected. If observations vary more than a simple count model expects, over-dispersion can matter: uncertainty may be larger than a model that assumes tightly clustered counts would suggest. Repeated events within participants can also make observations dependent rather than independent. These are general statistical considerations, not methods confirmed for this study; the registry record does not report a count model, an over-dispersion assessment, or a repeated-event method.
How should the comparison be understood?
A direct comparison of the lacosamide and Other AED groups would need to account for the study's non-interventional design and the fact that allocation is not stated. In general, a crude difference compares observed group summaries without accounting for other factors. An adjusted comparison attempts to account for measured characteristics, but can only address factors that were collected and modeled appropriately. No adjusted estimates or covariates are reported. Since the primary endpoint results themselves are absent, no recalculated comparison can be made from the registry information described.
A confidence interval, in general, expresses the precision of an estimate under specified assumptions. A narrower interval indicates greater precision than a wider interval, but neither establishes that an association is causal. No confidence interval for the cardiovascular endpoint is reported in the registry record. No hypothesis test or p-value for that endpoint is reported either. The absence of these statistics means that statistical precision and evidence against a null hypothesis cannot be assessed from the posted outcome record.
What do the planning assumptions mean?
The record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The planned effect to detect is described as a stated fraction of the observed effect. For time-to-event planning, the method is described as calculating a total number of events using Schoenfeld; other planning results are described as participants per arm. Numerical planning estimates are not reported in the registry record.
In general, such calculations explore what study size would be needed under chosen assumptions. They are not observed power, do not describe the actual precision of an outcome result, and do not show that the original study was designed using those assumptions. The registry does not report its own sample-size justification, or establish that the planning illustration was part of the original study design. The observed effect needed as the basis for the illustration is not available in the reported primary endpoint results.
What can be inferred from the safety summaries?
The serious and other adverse-event summaries give counts affected and counts at risk for each group. In general, a count affected is a descriptive measure, and its interpretation depends on the registry's definitions and reporting procedures. The displayed figures should not be treated as an analysis of the primary cardiovascular endpoint, because the record does not identify them as such. Nor do the group summaries adjust for the non-randomized treatment allocation. The registry does not report whether the summaries include all follow-up or how incomplete observations were handled.
The listed serious-event term percentages are also descriptive. Percentages can be difficult to compare without knowing the denominator, rules for repeated events, and whether the same participant could contribute to more than one term. Those details are not reported in the registry record. The appropriate statistical reading is therefore to retain the reported counts and percentages as summaries, while avoiding conclusions about comparative risk, endpoint-specific effects, or causal safety differences.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary cardiovascular adverse-event outcome and a secondary psychiatric adverse-event outcome, for two outcome measures. It lists zero analyses. No results for either outcome are reported in the registry record, and no statistical plan for choosing, prioritizing, or testing outcomes is described.
When several outcomes are tested, general statistical practice may consider multiplicity: the more tests performed, the greater the chance of at least one false-positive finding if each test is interpreted in isolation. Methods such as adjustment or a prespecified hierarchy can address this issue, but the registry does not report whether any multiplicity strategy was planned or used. With no endpoint analyses posted, it is not possible to assess how multiplicity affected the reported findings.
The primary outcome population is named as the Safety Set. The record does not define the Safety Set or give the number included in the primary endpoint analysis. It also does not report missing-data amounts, reasons for missingness, imputation, censoring, or sensitivity analyses. Those omissions prevent assessment of how incomplete follow-up may have affected the safety summaries or intended endpoint comparison.
In general, missing observations can matter when the likelihood of being observed is related to treatment or outcome. The direction and size of any resulting bias depend on the missingness pattern and analysis choices; neither can be inferred from the information reported. The registry record also does not state whether interim analyses took place or describe a statistical analysis plan. These points should be treated as unreported rather than assumed to have been absent from study conduct.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Lacosamide | 78 | 511 | 15.3% |
| Other AED | 64 | 493 | 13.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Lacosamide | 359 of 511 |
| Other AED | 299 of 493 |
Most frequent serious adverse event terms
| Event term | Organ system | Lacosamide | Other AED |
|---|---|---|---|
| Convulsion | Nervous system disorders | 16 of 511 | 17 of 493 |
| Grand Mal Convulsion | Nervous system disorders | 3 of 511 | 11 of 493 |
| Epilepsy | Nervous system disorders | 7 of 511 | 3 of 493 |
| Headache | Nervous system disorders | 3 of 511 | 4 of 493 |
| Partial Seizures | Nervous system disorders | 1 of 511 | 5 of 493 |
| Dizziness | Nervous system disorders | 4 of 511 | 1 of 493 |
| Status Epilepticus | Nervous system disorders | 3 of 511 | 1 of 493 |
| Hyponatraemia | Metabolism and nutrition disorders | 1 of 511 | 2 of 493 |
| Seizure Cluster | Nervous system disorders | 2 of 511 | 1 of 493 |
| Depression | Psychiatric disorders | 2 of 511 | 1 of 493 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lacosamide | Other AED |
|---|---|---|---|
| Dizziness | Nervous system disorders | 108 of 511 | 45 of 493 |
| Fatigue | General disorders | 81 of 511 | 61 of 493 |
| Headache | Nervous system disorders | 53 of 511 | 26 of 493 |
| Diplopia | Eye disorders | 52 of 511 | 18 of 493 |
| Nausea | Gastrointestinal disorders | 47 of 511 | 23 of 493 |
| Vertigo | Ear and labyrinth disorders | 44 of 511 | 11 of 493 |
| Convulsion | Nervous system disorders | 21 of 511 | 15 of 493 |
| Depression | Psychiatric disorders | 13 of 511 | 20 of 493 |
| Tremor | Nervous system disorders | 20 of 511 | 12 of 493 |
| Vision Blurred | Eye disorders | 18 of 511 | 13 of 493 |
Serious events with the highest arm-level rate: convulsion (3.4%), grand mal convulsion (2.2%), epilepsy (1.4%), partial seizures (1.0%), headache (0.8%).
The registry's safety summary lists serious adverse events and other adverse events separately for the lacosamide and Other AED groups. For lacosamide, 78 participants were affected by serious adverse events among 511 at risk, and 359 were affected by other adverse events among 511 at risk. For Other AED, 64 were affected by serious adverse events among 493 at risk, and 299 were affected by other adverse events among 493 at risk. These are descriptive counts, not the primary cardiovascular endpoint results.
The serious-event terms listed include convulsion (3.4%), grand mal convulsion (2.2%), epilepsy (1.4%), partial seizures (1.0%), headache (0.8%), and dizziness (0.8%). The registry record does not report the denominator or detailed calculation rules for these percentages. It also does not report deaths in the safety summary.
Because allocation is not stated and the groups are not a like-for-like control comparison, these figures should not be interpreted as a causal comparison of treatment safety. They do not show the frequency of the predefined cardiovascular or psychiatric endpoint. Those endpoint results are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The study's purpose was to evaluate long-term safety and tolerability of add-on lacosamide in epilepsy patients with partial-onset seizures who were uncontrolled on current therapy. Its primary safety question focused on predefined cardiovascular treatment-emergent adverse events, with a psychiatric adverse-event outcome also listed. The registry record defines the event window and identifies the Safety Set as the primary outcome population.
What the posted record does show is that the study was completed, that enrollment was 1005, and that descriptive serious and other adverse-event summaries were recorded for the lacosamide and Other AED groups. It also lists several serious-event terms with percentages. These figures can be read as reported safety descriptions, but not as the missing cardiovascular endpoint analysis.
The record does not provide outcome-specific cardiovascular or psychiatric counts, estimates of comparative effects, confidence intervals, or hypothesis tests. It does not report an adjusted analysis. Thus, the available information cannot establish how the predefined endpoint differed between groups, how precisely a difference was estimated, or whether any observed group difference was attributable to treatment. The non-interventional design and unstated allocation further limit causal interpretation.
These limitations are about what can be concluded from the registry record, not proof that an outcome did or did not occur, or that analyses were never conducted outside the record. A completed study can have results that are not posted in the outcome fields. The appropriate conclusion is that the registry describes the study's monitoring objectives and includes general adverse-event summaries, while the primary and secondary endpoint findings are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates an important distinction in safety research: a stated outcome is not the same as a reported result. The registry defines a clinically focused cardiovascular event set, specifies a treatment-emergent window, and names the population for the primary assessment. Those details make the intended monitoring question understandable. Yet without outcome-specific findings, a reader cannot assess the frequency, comparative pattern, or precision of the endpoint result.
The non-interventional design also highlights why comparative safety summaries need careful interpretation. Patients receiving different add-on therapies may not be comparable at baseline or during follow-up. The record does not state how treatment was allocated and explicitly cautions that the arms are not a like-for-like control comparison. Descriptive differences between group summaries therefore cannot be treated as effects caused by the medicines.
The record also distinguishes event counts from broader adverse-event summaries. Serious and other adverse-event counts, and the listed serious-event terms, offer some descriptive information, but do not answer the predefined cardiovascular or psychiatric questions. Keeping these outcome definitions separate helps prevent a general safety summary from being mistaken for a specific endpoint analysis.
For biostatistical interpretation, the missing elements matter: endpoint results, analysis methods, uncertainty estimates, and information about missing observations are not reported in the registry record. The study is a useful example of how design, outcome definition, reporting completeness, and causal interpretation jointly determine what can be learned from a safety record.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation for interpreting this study is that the registry lists zero analyses and does not report results for the primary cardiovascular endpoint or the secondary psychiatric endpoint. The serious and other adverse-event summaries do not fill that gap, because they are not identified as analyses of either predefined outcome. No confidence intervals, hypothesis tests, or adjusted estimates are reported.
The study is non-interventional, treatment allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. The record does not describe adjustment for differences between treatment groups, so any causal interpretation of their descriptive summaries would be unsupported. The record also does not report details of the sample-size justification, interim analyses, or statistical analysis plan.
The Safety Set is named for the primary outcome, but its membership is not defined in the record. Missing-data amounts and handling, follow-up completeness, repeated-event counting, and the denominator for the listed serious-event percentages are not reported in the registry record. Deaths are not reported in the safety summary. These gaps limit interpretation of both the endpoint and the broader adverse-event descriptions.
The registry describes a planning illustration based on an observed effect, but does not report numerical planning estimates or the endpoint results underlying such an effect. Those planning assumptions should not be mistaken for the original study design or for observed statistical power. Overall, the available record supports a description of the study's aims and some general safety summaries, but not a precise or causal comparison of the predefined outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Post-Authorization Safety Study to Assess the Safety of Vimpat as add-on Therapy in Patients With Partial-onset Seizures — NCT00771927.
- Registry record last updated 2014-10-27; status last verified 2013-05.
- Results first posted 2013-04-22.
- 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.
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18. Record Summary
NCT00771927 is a completed, non-interventional post-authorization safety study sponsored by UCB Pharma. It enrolled 1005 and evaluated add-on lacosamide in epilepsy patients aged 16 years and older with partial-onset seizures who were uncontrolled on current therapy, alongside a group receiving another approved add-on antiepileptic drug.
The primary outcome was the number of predefined cardiovascular treatment-emergent adverse events from baseline up to 12 months. A predefined psychiatric adverse-event outcome was also listed. The registry record lists zero analyses, and results for these outcomes are not reported in the registry record. Descriptive serious and other adverse-event figures are present, but they are not the missing endpoint analyses. Allocation is not stated, and the groups are not a like-for-like control comparison.