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 A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304) (NCT01146951), a randomized phase 3 study. The primary outcome is Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01146951 |
| Phase | Phase 3 |
| Condition | Lennox-Gastaut Syndrome |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 66 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Eisai Limited |
| Results posted | Yes |
2. Clinical Question
Population
Participants with Lennox-Gastaut syndrome were enrolled. The registry reports 66 participants overall. For the primary outcome, the listed analysis population is the full analysis set, with 28 participants in the rufinamide group and 30 in the placebo group. The registry’s description of exclusions from that set is incomplete, so the full details of who was eligible for analysis are not reported in the registry record.
Intervention
The intervention was rufinamide (E2080), described in the study summary as combination therapy. The arm description does not give additional details about the treatment regimen, and those details are not reported in the registry record.
Comparator
The comparator was placebo. The study is identified as placebo-controlled, randomized, parallel-group, and quadruple-masked. The registry does not explain which roles were included in the masking.
Primary question
The primary question concerned percent change in tonic-atonic seizure frequency per 28 days from the baseline observational period to the end-of-treatment period. The reported comparison assessed whether the distribution of this outcome differed between the rufinamide and placebo groups.
The primary outcome combines tonic and atonic seizures into one frequency measure. The registry’s brief study summary frames the study as seeking to confirm superior efficacy of rufinamide combination therapy compared with placebo. The posted primary analysis gives a rank-based comparison of the two groups, rather than a comparison of means.
Four secondary outcomes are listed: achieving a 50% reduction in tonic-atonic seizure frequency, percent change in total seizure frequency, percentage change in seizures other than tonic-atonic seizures, and Clinical Global Impression of Change. Their results are not included in the available primary-result details, so their estimates and the conclusions that could be drawn from them are not reported in the registry record.
3. Trial Design
The study is listed as a phase 3 randomized trial with a parallel-group design and quadruple masking. It compared rufinamide (E2080) with placebo in Lennox-Gastaut syndrome. The sponsor is Eisai Limited. The registry lists the study as completed, with enrollment of 66; the start is recorded as 2010-06 and primary completion as 2011-08.
The primary outcome used an observational baseline period of 28 days and an end-of-treatment period of 28 days. Seizure frequency was recorded in a seizure diary. The registry states that seizure classification followed the International League Against Epilepsy classification, and that the person recording the diary monitored the participant and recorded seizures consistently during the study. Other details of the treatment schedule, duration beyond the outcome’s stated periods, allocation procedure, and masking procedures are not reported in the registry record.
The primary outcome analysis included 28 participants assigned to rufinamide and 30 assigned to placebo. The registry describes the analysis population as a full analysis set, but its definition is cut off after listing some exclusions. The precise rules used to determine inclusion in this set are therefore not reported in the registry record.
The registry lists five outcome measures and 11 analyses. It identifies four secondary outcomes in addition to the primary outcome, but the results for those secondary measures are not present in the available results. The listed primary comparison uses a Wilcoxon (Mann-Whitney) method and reports a Hodges-Lehmann estimate, a 90% confidence interval, and a p-value. The registry does not report a detailed statistical analysis plan, sample-size justification, interim-analysis plan, or multiplicity procedure.
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: Of n= 66 who started Observation Period, 7 discontinued from study. Primary reasons were deviation of the inclusion/ exclusion criteria (n=5), untoward event before study treatment (n=1) \& other (n=1). Of 59 participants, 58 were included in full analysis set (FAS). 1 participant (E2080 group) was excluded due to inappropriate diagnosis of disease.
Overall Study
| Stage | Rufinamide (E2080) | Placebo |
|---|---|---|
| STARTED | 29 | 30 |
| COMPLETED | 25 | 29 |
| NOT COMPLETED | 4 | 1 |
Reasons for not completing this period:
| Reason | Rufinamide (E2080) | Placebo |
|---|---|---|
| Adverse Event | 4 | 1 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) is defined as participants who were registered for the Treatment Period and excludes those listed below. Participants who did not meet the inclusion criterion related the target disease, participants who did not take the study drug, participants without any evaluable efficacy data after the start of study treatment.
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: One subject from the Rufinamide (E2080) group was excluded from the FAS because of the inappropriate diagnosis of the disease, dropping the total number from 29 to 28 participants.
| Characteristic | Unit | Rufinamide (E2080) | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 28 | 30 | 58 | |
| Age, Continuous | years | 16.0 (SD 7.1) | 13.9 (SD 6.1) | 14.9 (SD 6.6) |
| Sex: Female, Male: Female | Participants | 11 | 11 | 22 |
| Sex: Female, Male: Male | Participants | 17 | 19 | 36 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change in Tonic-Atonic Seizure Frequency From Baseline (Per 28 Days), measured over Baseline (28 day observational period) and End of Treatment (28 day treatment period).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | Percent Change |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was percent change in tonic-atonic seizure frequency per 28 days. Tonic and atonic seizure frequencies were added to form the tonic-atonic frequency. The baseline was the frequency during the 28-day observation period; the post-treatment value was the frequency during the 28-day treatment period. The percent change was defined as 100 multiplied by the difference between post-treatment and baseline values, divided by baseline.
Under this definition, a negative percent change indicates a lower recorded frequency in the treatment period than in the baseline period; a positive value indicates a higher recorded frequency. This direction follows directly from the registry’s formula and does not by itself establish the cause of a change.
Combining the two seizure types yields a single measure focused on tonic-atonic seizure frequency. Such a prespecified clinical measure can make a comparison more focused than treating every seizure category as the primary outcome. In general, a baseline-to-treatment change measure also provides a common scale for describing change across participants with different starting frequencies. Its interpretation depends on reliable baseline and treatment-period recording, and on the analysis population and comparison method.
The registry reports the primary outcome as a median with full range for each group and uses a rank-based between-group analysis. The reason for selecting this endpoint and the planned rationale for its summary and analysis are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The median percent change was -24.2 in the rufinamide group and -3.25 in the placebo group. The full ranges were -93.5 to 27.2 and -81.6 to 151.9, respectively. These descriptive summaries show that values varied widely within both groups, and that the observed ranges included both negative and positive changes. The medians describe the middle observations; they do not describe every participant’s experience or the shape of the entire outcome distribution.
The registry’s rank-based comparison reported a Hodges-Lehmann estimate of -26.65, with a 90% confidence interval from -40.30 to -11.80, and p = 0.003. The estimate is a location-shift summary for the comparison, not a difference between the two displayed medians. Its negative direction is consistent with lower percent-change values in the rufinamide group relative to placebo under the reported comparison. The interval gives a range of values compatible with the estimate under the method’s assumptions; it is not a range containing 90% of individual participant outcomes.
The p-value describes how incompatible the observed rank-based evidence is with the null hypothesis used by the test, assuming the analysis model and test conditions hold. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The confidence interval expresses uncertainty about the estimated group contrast. Because the registry reports a 90% interval, it should not be described as a 95% interval.
The reported interval lies entirely on the negative side of zero, while the p-value is 0.003. These findings indicate a statistically distinguishable group contrast under the reported analysis. They do not, by themselves, establish the clinical meaning of the difference, the durability of any change, or an effect for every participant. The broad ranges and differing participant counts also matter when interpreting the summaries.
This interpretation is limited to the primary endpoint and the analysis displayed in the registry. Results for the four listed secondary outcomes are not reported in the registry record. The registry also does not provide enough detail to assess all analysis choices, missing-outcome handling, or multiplicity adjustments. Those omissions limit how completely the primary result can be placed in the context of the full study.
9. Statistical Methods Explained
What does the rank-based test compare?
The registry reports a Wilcoxon (Mann-Whitney) test for the two groups. In general, this test uses the ordering of observed values rather than comparing group means directly. Values from both groups are ranked together, and the ranks are used to assess whether one group tends to have higher or lower values than the other. This approach can be useful when a continuous outcome is skewed or contains extreme observations, although it still relies on appropriate study design and independent observations.
A rank-based test is not simply a test of whether the medians differ. It assesses a broader distributional contrast. A difference in distribution shape can affect its interpretation, so a location-shift interpretation is clearest when the distributions have reasonably similar shapes. The registry reports group medians and full ranges, but does not report diagnostic checks or distribution plots in the statistical description.
What is the Hodges-Lehmann estimate?
The reported Hodges-Lehmann estimate is -26.65. In general, this estimator summarizes a between-group location contrast using pairwise differences across the two groups. It is related to the rank-based comparison and should not be read as the subtraction of the two group medians. Here, the group medians are -24.2 and -3.25, while the reported contrast estimate is -26.65. These are different summaries with different interpretations.
The direction depends on the ordering used for the groups and on the outcome scale. Since lower percent-change values represent greater decreases from baseline under the endpoint formula, the negative contrast is in the direction of lower values for rufinamide relative to placebo. This is a statistical description, not a statement about the clinical importance or cause of the observed difference.
How should the confidence interval be read?
The reported 90% confidence interval extends from -40.30 to -11.80. In general, a confidence interval is produced by a method that would cover the target parameter at its stated rate over repeated studies under the method’s assumptions. It communicates uncertainty about the estimated contrast. It does not mean that 90% of participant outcomes fall inside the interval, and it is not a probability statement about this particular estimate after the data have been observed.
The interval’s endpoints are both negative, which is consistent with a negative group contrast under the reported method. The registry does not report additional sensitivity analyses that would show how robust this interval is to alternative analysis choices.
What does the p-value contribute?
The reported p-value is 0.003. In general, a p-value measures how unusual data at least as discordant with a stated null hypothesis would be if that hypothesis and the test assumptions were true. It does not give the probability that the null hypothesis is correct, and it does not quantify clinical importance. The p-value and confidence interval address related but distinct questions: one summarizes evidence relative to a null, while the other gives an uncertainty interval for the contrast.
The registry identifies the test and p-value but does not provide the complete prespecified testing strategy. It is therefore not reported in the registry record whether this comparison was adjusted for other outcomes or analyses.
Why might ranks be useful for this outcome?
In general, seizure-frequency change measures can have uneven distributions, particularly when participant-level changes differ substantially. A rank-based method does not require the same normal-distribution model used by a simple comparison of means. It can therefore be a reasonable option for outcomes where extreme values or skewness are a concern. However, it does not eliminate the need to consider missing data, baseline comparability, outcome recording, and the analysis population.
The full ranges extend from -93.5 to 27.2 in the rufinamide group and from -81.6 to 151.9 in the placebo group. These ranges indicate that observations were dispersed, but ranges alone do not establish the distribution shape or explain why individual observations differ. The registry does not report measures such as standard deviations or a detailed account of outlying observations for this endpoint.
What can be inferred from the group summaries?
The median is a measure of central location: half of the observations lie at or below it and half at or above it, subject to the handling of ties and the sample’s size. The full range reports the smallest and largest observed values, but is sensitive to extreme observations and says little about how values are distributed between the endpoints. In general, showing both central summaries and spread helps prevent a median from being mistaken for a complete account of participant outcomes.
The reported analysis population contains 28 participants in the rufinamide group and 30 in the placebo group. The registry gives an overall enrollment of 66, but the primary analysis counts do not account for every enrolled participant. The detailed reasons and rules for this difference are not reported in the registry record. The trial’s allocation and analysis populations should therefore not be treated as interchangeable.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Wilcoxon (Mann-Whitney) | Hodges-Lehmann -26.65 | -40.30 to -11.80 | 0.003 |
The registry reports the study’s primary comparison as a Wilcoxon (Mann-Whitney) analysis with a Hodges-Lehmann estimate of -26.65, a 90% confidence interval from -40.30 to -11.80, and p = 0.003. This is the stated analysis associated with the posted primary outcome. The descriptive group results are medians and full ranges, not a separate estimate of the same contrast.
No distinct recalculated estimate is reported in the registry record, so a numerical comparison between a sponsor analysis and a separate recalculation cannot be made from these results. The record does not flag a discrepancy between analyses. The distinction is still important: an unadjusted recalculation from summary statistics, if available, would not necessarily reproduce a rank-based analysis using participant-level data. Differences in estimand, method, or available data can lead to different answers.
In general, a sponsor’s prespecified analysis is the principal result to interpret when it is documented and tied to the trial’s analysis plan. The registry does not include enough detail to establish all elements of that plan or to assess whether this analysis was prespecified. The reported primary analysis and its uncertainty should therefore be described as posted, without claiming that an unreported recalculation confirms or overturns it.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome and four secondary outcomes, and reports 11 analyses across five outcome measures. Multiple outcomes and analyses can create a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase if each is assessed without adjustment. In general, a prespecified testing hierarchy or adjustment method can help control this issue. The multiplicity strategy is not reported in the registry record.
The available primary result includes a p-value of 0.003 and a 90% confidence interval. Without the statistical analysis plan, it is not possible to determine whether this interval and p-value were part of a primary testing sequence, whether other analyses were exploratory, or whether any adjustment was planned. The four secondary outcomes are named, but their estimates and tests are not reported in the registry record. Their absence prevents a complete assessment of the pattern of outcomes.
The primary analysis population is described as the full analysis set, with 28 participants in the rufinamide group and 30 in the placebo group. The definition begins by listing exclusions but is incomplete. The registry does not report the full inclusion and exclusion rules, how missing seizure-diary observations were handled, or whether any imputation or other missing-data method was used. It is also not reported in the registry record how many participants had incomplete diary information or the reasons for any missing data.
In general, missing outcome data can affect both the estimate and its precision, especially if the likelihood of missingness is related to outcome or treatment. A full account of missingness and analysis-population rules helps readers judge whether the analyzed participants represent those randomized. The overall enrollment is 66, while the primary endpoint analysis lists 28 and 30 participants; the record does not explain this difference in full. These details limit assessment of attrition, analysis integrity, and the extent to which the primary result reflects the randomized groups.
12. 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 |
|---|---|---|---|
| Rufinamide (E2080) | 1 | 29 | 3.4% |
| Placebo | 1 | 30 | 3.3% |
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 |
|---|---|
| Rufinamide (E2080) | 27 of 29 |
| Placebo | 21 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | Rufinamide (E2080) | Placebo |
|---|---|---|---|
| Drug Eruption | Skin and subcutaneous tissue disorders | 1 of 29 | 1 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rufinamide (E2080) | Placebo |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 9 of 29 | 9 of 30 |
| Status Epilepticus | Nervous system disorders | 8 of 29 | 5 of 30 |
| Decreased Appetite | Metabolism and nutrition disorders | 6 of 29 | 2 of 30 |
| Somnolence | Nervous system disorders | 6 of 29 | 2 of 30 |
| Vomiting | Gastrointestinal disorders | 5 of 29 | 1 of 30 |
| Upper Respiratory Tract Infection | Infections and infestations | 2 of 29 | 4 of 30 |
| Dental Caries | Gastrointestinal disorders | 2 of 29 | 0 of 30 |
| Nausea | Gastrointestinal disorders | 2 of 29 | 0 of 30 |
| Rhinitis | Infections and infestations | 1 of 29 | 1 of 30 |
| Gastroenteritis | Infections and infestations | 0 of 29 | 2 of 30 |
Serious events with the highest arm-level rate: drug eruption (3.4%).
The serious adverse event counts list 1 affected participant among 29 at risk in the rufinamide group and 1 among 30 at risk in the placebo group. These are participant counts, not counts of all event episodes. With only one affected participant in each group, the figures provide limited precision for comparing uncommon events. They do not establish that the groups have the same safety profile.
The registry also lists “Drug Eruption” at 3.4% among the top serious terms. The record does not specify the group for this term in the posted details, so it should not be assigned to either group from this information alone. Other adverse events affected 27 of 29 participants in the rufinamide group and 21 of 30 in the placebo group. These broader counts are distinct from the serious adverse event counts.
Deaths are not reported in the registry record. The adverse-event figures are descriptive and do not establish causation. Interpretation is limited by the small number of serious-event participants and by the absence of further detail about event types, timing, severity, and attribution in the registry record.
13. What the Result Does, and Does Not, Mean
The posted primary analysis describes a between-group difference in percent change in tonic-atonic seizure frequency. The rufinamide group had a median change of -24.2 and the placebo group had a median change of -3.25. The rank-based comparison estimated a location contrast of -26.65, with a 90% confidence interval from -40.30 to -11.80 and p = 0.003. Together, these figures describe the direction and statistical uncertainty of the observed primary comparison.
They do not mean that every participant experienced a decrease, or that the group medians describe each participant’s outcome. The observed ranges include both negative and positive values in both groups. The estimate and interval also do not show that the outcome difference is clinically important; the registry does not report a threshold for clinical importance.
These results do not establish why the groups differed, whether the difference persisted beyond the treatment period, or what happened for outcomes not reported. The primary endpoint compares baseline with the end-of-treatment period, each defined over 28 days. The registry does not provide a longer-term result for this endpoint. It also does not report results for the listed secondary outcomes, so those outcomes cannot be used to corroborate or qualify the primary finding.
In general, a randomized, masked comparison can support a more informative assessment of group differences than an uncontrolled observation, but interpretation still depends on the conduct of the trial, outcome measurement, analysis choices, and missing data. The registry identifies randomization and quadruple masking but does not provide all procedural details needed to assess them fully. The incomplete analysis-population definition and unreported missing-data handling further limit assessment.
The result is therefore a statistical description of the posted primary endpoint comparison in the analyzed participants. It is not a guarantee of an individual outcome, a complete account of all trial outcomes, or a substitute for clinical judgment.
14. Why This Trial Matters Statistically
This study illustrates why an endpoint’s construction and its analysis method both matter. The primary measure combines tonic and atonic seizure frequencies and expresses change relative to a baseline period. Because negative values correspond to a decrease under the stated formula, the direction of the group contrast can be interpreted from the endpoint definition. Without that definition, a negative estimate might be easy to misread.
The comparison also demonstrates why a group-level estimate should not be confused with a pair of group medians. The reported Hodges-Lehmann estimate comes from a rank-based method and summarizes a different feature of the data than the medians. The confidence interval and p-value add information about uncertainty and compatibility with a null hypothesis, but neither replaces consideration of the observed spread or the clinical importance of the contrast.
The registry’s result also highlights the value of complete reporting. The overall enrollment is 66, while the primary analysis includes 28 and 30 participants. The full analysis-set definition, missing-data handling, multiplicity approach, and results for the secondary outcomes are not reported in the registry record. Those elements are important for understanding how the primary finding fits into the study’s complete evidence.
For biostatisticians and clinical researchers, the practical lesson is to read endpoint definition, estimand, analysis population, test, effect estimate, and uncertainty together. A statistically clear result can still have limits when the wider analysis plan and outcome set are not available. The record supports interpretation of the posted primary comparison, while leaving important questions about the broader study analysis unresolved.
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 registry record does not provide a complete definition of the full analysis set. It begins listing exclusions, but the description ends before the full set of rules is given. Although 66 participants were enrolled, the primary endpoint results include 28 in the rufinamide group and 30 in the placebo group. The record does not fully explain the difference between enrollment and the analyzed population.
Missing-data methods are not reported in the registry record. For an endpoint derived from seizure diaries, completeness and consistency of recording are relevant to interpretation. The registry describes diary recording and classification, but does not report how incomplete diaries, missed observations, or participants without evaluable outcomes were handled in the primary analysis.
The registry names four secondary outcomes and reports 11 analyses, but the results for the secondary outcomes are not included in the posted outcome details. A multiplicity plan and interim-analysis plan are not reported in the registry record. The stated statistical analysis plan, sample-size justification, and rationale for selecting the primary method are also not reported. This makes it difficult to assess the full scope of testing and the planning assumptions behind the study.
The primary results give medians, full ranges, and a rank-based contrast, but do not include a detailed description of the outcome distribution or participant-level data. The treatment regimen and fuller details of randomization and masking are not reported in the registry record. The safety details are also limited: deaths are not reported, and the group attribution of the listed serious term is not specified in the posted details. These limitations do not negate the reported comparison, but they constrain how fully it can be evaluated.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304) — NCT01146951.
- Registry record last updated 2018-01-24; status last verified 2018-01.
- Results first posted 2013-11-21.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry describes a completed, randomized, parallel-group, quadruple-masked phase 3 study sponsored by Eisai Limited. It enrolled 66 participants with Lennox-Gastaut syndrome and compared rufinamide (E2080) with placebo. The study start is recorded as 2010-06 and primary completion as 2011-08.
The primary endpoint was percent change in tonic-atonic seizure frequency per 28 days, from a 28-day baseline observational period to a 28-day treatment period. The reported rank-based comparison gave a Hodges-Lehmann estimate of -26.65, a 90% confidence interval from -40.30 to -11.80, and p = 0.003. The analysis included 28 participants in the rufinamide group and 30 in the placebo group.
Four secondary outcomes are listed, but their results, the full analysis-population definition, missing-data handling, and multiplicity approach are not reported in the registry record. These omissions limit a complete appraisal of the trial while leaving the posted primary comparison interpretable on its stated terms.