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 Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures (NCT00692003), a randomized phase 3 study. The primary outcome is Number of Participants Considered Responders as Assessed During the Maintenance Period.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00692003 |
| Phase | Phase 3 |
| Condition | Epilepsy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 21 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eisai Limited |
| Results posted | Yes |
2. Clinical Question
Population
People with epilepsy and primary generalised tonic-clonic seizures were the population of interest. The registry record does not report detailed eligibility criteria or participant characteristics.
Intervention
The intervention was zonisamide, described in the study title as adjunctive treatment. The registry record does not give details of the dose or background treatments.
Comparator
The comparator was placebo. The study was randomized, double-blind and parallel-group, but the registry record does not describe the allocation procedure or the specifics of masking.
Primary question
The primary endpoint was the number of participants considered responders during the maintenance period. A responder was defined by at least a 50% decrease in primary generalised tonic-clonic seizure frequency relative to baseline. The registry record says that the sponsor terminated the study early and no formal analyses were conducted.
The study was intended to assess the efficacy and safety of adjunctive zonisamide for this seizure type. Its registered endpoint makes the treatment question concrete: it asks how many participants met a prespecified threshold for seizure-frequency reduction over the maintenance period. However, a defined endpoint is not itself an estimate of treatment effect. The record does not report analyzed responder counts, an effect estimate, uncertainty around an estimate, or a formal comparison between the randomized groups. Consequently, the registry information does not establish how the groups compared on the primary question.
3. Trial Design
The registry identifies this as a Phase 3, randomized, double-blind, parallel-group study with zonisamide and placebo interventions. The official title describes it as a multicentre study. Its registered enrollment is 21. That registry enrollment figure does not establish how many participants were assigned to each arm or included in any particular analysis.
The study started on 2008-08-01, and the primary completion date is recorded as 2008-11. Its status is TERMINATED. The registry summary says the sponsor ended the study early and that no formal analyses were conducted. The record does not explain the reason for termination beyond attributing it to the sponsor, nor does it describe whether the termination followed a prespecified rule.
The planned treatment assessment included a baseline interval and a maintenance phase. The primary endpoint description defines baseline as Week -8/-4 to Week 0 and the maintenance phase as Week 4 to Week 16. It describes response during the 12 week maintenance period. Participants were to record seizures in diaries dispensed at screening; the description says diaries were maintained through titration and maintenance until an Early termination Visit at Week 16. These are endpoint-description details and do not demonstrate that every participant completed those periods or visits.
The registry summary describes a total trial duration of 5.5-6.5 months and says participants who completed the study would be eligible for an open-label extension under a separate protocol. Whether anyone entered that extension is not reported in the registry record. Details of dose, titration schedule, allocation ratio, sites, and treatment adherence are also not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Twenty-one subjects were screened and 14 participants did not continue the study after screening. Seven participants entered the study but 1 participant did not receive any treatment. Consequently, 6 participants were enrolled and treated during the study. None of the 6 subjects completed treatment \& all discontinued due to the Sponsor's decision.
Overall Study
| Stage | Zonisamide | Placebo |
|---|---|---|
| STARTED | 5 | 1 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 5 | 1 |
Reasons for not completing this period:
| Reason | Zonisamide | Placebo |
|---|---|---|
| Sponsor Decision | 5 | 1 |
Analysis population for the primary outcome, as defined in the registry: Due to early termination of the study by the Sponsor, no formal analyses were conducted.
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.
| Characteristic | Unit | Zonisamide | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 5 | 1 | 6 | |
| Age, Continuous | years | 38.4 (SD 18.66) | 27.0 (SD NA) | 36.5 (SD 17.33) |
| Sex: Female, Male: Female | Participants | 3 | 0 | 3 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Considered Responders as Assessed During the Maintenance Period, measured over Baseline (Week -8/-4 to Week 0) and Maintenance Phase (Week 4 to Week 16).
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the number of participants considered responders during the maintenance period. The endpoint description defines a responder as a participant whose primary generalised tonic-clonic seizure frequency decreased by at least 50% from baseline. The comparison of seizure frequency was based on 28-day frequency during the period from Week 4 to the Week 16 visit versus the baseline period from Week -8/-4 to randomization at Week 0. The description says response was assessed using seizure diaries kept by participants or their parent or caregiver.
This is a threshold-based endpoint: it classifies each participant as meeting or not meeting the response definition, then counts responders. In general, a threshold can make an outcome easier to interpret as a participant-level category, but it also compresses information. Participants just above and well above the threshold both count as responders, while their different degrees of change are not represented by the responder count. A separate registered secondary outcome was absolute change from baseline in 28-day seizure frequency, which addresses change on a continuous scale.
The endpoint is useful for framing the intended comparison, but the registry record reports no formal analyses. It does not report the analyzed number of responders in either group or a treatment-effect estimate. Thus, the endpoint definition is available, but a result answering the comparison is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that a randomized, double-blind, placebo-controlled study was planned to assess adjunctive zonisamide, and it defines a primary responder endpoint. It also states that the sponsor terminated the study early and that no formal analyses were conducted. The central statistical consequence is that the planned question cannot be answered from the posted results: there is no formal comparison of responder counts between the zonisamide and placebo groups.
The record does not report the number of participants who met the responder definition, the number assessed for that endpoint, or an estimate of the difference between groups. It also does not report a confidence interval or a p-value for the primary endpoint. Those omissions mean there is no reported estimate of the direction or precision of a treatment contrast. The absence of a reported analysis is not evidence that the groups had the same outcomes, and it does not establish that either group had better outcomes.
The registered enrollment is 21, but that figure should not be mistaken for an analyzed population. The adverse-event entries separately indicate participants at risk for those safety summaries; they do not establish the numbers randomized, treated, or assessed for the efficacy endpoint. The registry does not report group-specific enrollment or the number with usable seizure diaries. Therefore, the extent of missing endpoint data and the population contributing to any intended efficacy analysis are not reported in the registry record.
In general, a confidence interval communicates the range of effect estimates reasonably compatible with the data and the analysis assumptions. Without an estimate and interval, precision cannot be assessed. A p-value, if reported, would address compatibility with a specified null hypothesis under an analysis model; it would not by itself describe the size or clinical relevance of an effect. Neither is reported for the primary endpoint.
The posted safety counts are descriptive and limited. They show serious adverse events affecting 0 of 1 participants at risk in the placebo group and 0 of 5 in the zonisamide group. Other adverse events affected 0 of 1 in the placebo group and 2 of 5 in the zonisamide group. These entries do not replace the missing efficacy analysis, and the small reported at-risk counts limit how much can be inferred about safety. Death counts are not reported in the registry record.
Overall, the most defensible interpretation is that the registry describes the intended comparison and records a premature termination without formal analyses. It does not provide an analyzed efficacy result or sufficient information to judge the precision of a treatment comparison. Any broader claim about comparative effects would go beyond the results reported in the registry record.
9. Statistical Methods Explained
The statistical methods that can be described are those implied by the registered endpoint and the limited summary information. The registry record does not report the formal analysis plan, specific statistical tests, model specifications, or estimates. Any discussion of general statistical concepts below is general explanation, not a description of methods confirmed to have been used in this study.
What does the responder endpoint count?
The primary endpoint counts participants who crossed a stated threshold for reduction in seizure frequency. The threshold was a decrease of at least 50% from baseline, assessed during the maintenance period. Such an endpoint converts an individual change into a binary classification: responder or not responder. The number of responders can then be compared between randomized groups, provided the relevant counts and analysis population are available. They are not reported for this study.
In general, a binary endpoint can be summarized by the number meeting the definition and the number assessed in each group. A comparison might be expressed using a difference or ratio of response probabilities, with an interval to describe uncertainty. Those quantities cannot be reconstructed from the registry entry because the efficacy responder counts and analysis denominators are not reported. No unadjusted recalculation is available from the posted summary statistics.
Why define a baseline period?
The endpoint compares seizure frequency in the maintenance period with a baseline period. In general, a baseline reference gives a way to define within-participant change. A comparison between randomized groups is still needed to distinguish the observed change under one assignment from change under the comparator. Changes from baseline within a single group do not, by themselves, estimate the difference attributable to the assigned treatment, because change can also reflect factors shared across groups or time.
The endpoint description identifies the periods used for the comparison, but the registry record does not report participant-level frequency data, group summaries, or an analyzed comparison. It also does not report how incomplete diary entries were handled, how baseline frequency was calculated when diary information was incomplete, or whether any adjustments were planned.
What would uncertainty measures add?
In general, a confidence interval adds information about the precision of an estimated group contrast. A narrow interval indicates more precision under the chosen analysis assumptions; a wide interval indicates less. The interval does not guarantee that the true effect lies within its bounds, and its interpretation depends on the method used. Because no primary-effect estimate or confidence interval is reported, the precision of the intended comparison cannot be evaluated.
A hypothesis test may produce a p-value, but a p-value is not a measure of the probability that a treatment works, nor does it convey the size of an effect. Its interpretation depends on the analysis and the hypothesis being tested. The record reports no formal analyses and no primary endpoint p-value. The statistical plan, including any planned test or model, is not reported in the registry record.
How should the planning illustrations be understood?
The sample-size assumptions describe planning illustrations based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. Such calculations are planning scenarios rather than outcomes from the trial. In general, a planning calculation asks what sample size might be needed under chosen assumptions; it does not describe the evidence generated by participants in a completed analysis. It is not observed power.
The registry record provides no analyzed effect estimate for the primary endpoint, and the endpoint was not reduced to a single comparison. It therefore does not provide a reported primary-effect result on which to base an interpretation of the intended comparison. The registry record does not report the trial's own sample-size justification or statistical plan. Any planning illustration must be kept distinct from a formal result of this terminated study.
What does early termination mean statistically?
Early termination and the absence of formal analyses leave the efficacy question unresolved in this registry entry. In general, a smaller or incomplete dataset can yield less precise estimates, but the record does not report enough about participant flow or endpoint data to quantify that issue for this study. No conclusion about the impact of termination on estimates can be made from the information recorded.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures: the primary responder count and the secondary outcome of absolute change from baseline in 28-day primary generalised tonic-clonic seizure frequency. It records zero analyses. The sponsor terminated the study early, and the endpoint description states that no formal analyses were conducted.
When a study assesses multiple outcomes or makes multiple comparisons, multiplicity can arise: the chance of at least one apparently notable result can increase if many hypotheses are tested without an appropriate plan. In general, a statistical plan may define a primary hypothesis, a testing order, or an adjustment strategy. The registry record does not report whether such procedures were planned for this study. Because no formal analyses were conducted, there are no reported outcome-specific tests or estimates to interpret.
The endpoint description mentions seizure diaries, but completeness of those records and the handling of missing diary data are not reported in the registry record. The record also does not specify an efficacy analysis population, such as whether analyses were intended to include all randomized participants or only participants with evaluable data. It does not report participant disposition, exclusions, protocol deviations, or the number assessed for either outcome.
These gaps matter because endpoint counts and denominators depend on who was included and how incomplete observations were treated. Without those details, readers cannot assess whether the intended analysis population was preserved, whether missingness could have affected the results, or whether the secondary outcome was analyzed. The available record supports no adjustment or missing-data procedure being attributed to the study.
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 |
|---|---|---|---|
| Placebo | 0 | 1 | 0.0% |
| Zonisamide | 0 | 5 | 0.0% |
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 |
|---|---|
| Placebo | 0 of 1 |
| Zonisamide | 2 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Zonisamide |
|---|---|---|---|
| Fatigue | General disorders | 0 of 1 | 1 of 5 |
| Gait disturbance | General disorders | 0 of 1 | 1 of 5 |
| Nasopharyngitis | Infections and infestations | 0 of 1 | 1 of 5 |
| Urinary tract infection | Infections and infestations | 0 of 1 | 1 of 5 |
| Dizziness | Nervous system disorders | 0 of 1 | 1 of 5 |
| Postictal headache | Nervous system disorders | 0 of 1 | 1 of 5 |
The registry lists serious adverse events for participants at risk in each group. In the placebo group, 0 of 1 participants at risk were affected; in the zonisamide group, 0 of 5 participants at risk were affected. These are counts of affected participants, not a complete account of the kinds of events, their timing, or their relationship to treatment. No serious adverse-event terms are listed.
For other adverse events, the registry lists 0 of 1 participants at risk in the placebo group and 2 of 5 in the zonisamide group. These counts should be read in the context of the reported at-risk groups and the terminated study. They are not a comprehensive comparison of safety, and they do not establish how likely an event would be in a larger or different population. The registry record does not report event-level descriptions, severity details, or whether participants experienced more than one event.
Death counts are not reported in the registry record; a blank or null entry should not be interpreted as a count of zero. In general, when event counts and denominators are limited, estimates of event frequency are imprecise and comparisons are difficult to interpret. The posted safety information is descriptive, with no formal analysis reported.
12. What the Result Does, and Does Not, Mean
The study record documents a randomized, double-blind, placebo-controlled trial intended to examine adjunctive zonisamide for primary generalised tonic-clonic seizures. It specifies a responder endpoint based on a decrease of at least 50% in seizure frequency during maintenance relative to baseline. This makes the planned outcome and comparison question clear.
What the record does not provide is an analyzed answer. It states that the sponsor terminated the study early and that no formal analyses were conducted. Responder counts, group comparisons, effect estimates, confidence intervals, and p-values for the primary outcome are not reported in the registry record. Therefore, these results do not show whether the zonisamide and placebo groups differed on the primary endpoint or how precisely any difference might have been estimated.
The registry enrollment of 21 is not a substitute for endpoint data. It does not tell readers how many participants were assigned to each group, how many completed the maintenance period, or how many contributed usable diary information. The safety entries give at-risk counts for their own summaries but do not define the efficacy analysis population.
In general, an absence of a formal result is different from evidence of no effect. It is also different from evidence of benefit or harm. No treatment conclusion can be drawn from a defined endpoint alone, and the limited adverse-event counts do not resolve the efficacy question. Any statement that the trial demonstrated or ruled out a comparative effect would exceed the registry record.
The study is best understood as a registered clinical question with a documented endpoint and limited descriptive safety information, but without a formal efficacy result. The record does not report why the sponsor terminated the study, nor does it provide details that would support a more specific account of how termination affected the planned analysis.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction in clinical-trial interpretation: a carefully stated endpoint is not the same as a reported statistical result. The registry defines a responder using a clear threshold and identifies the baseline and maintenance periods. Those details explain what the study intended to measure, but they do not provide the responder counts or a comparison between randomized groups.
For biostatistical interpretation, the termination status and absence of formal analyses are central. A reader cannot infer an effect estimate from the existence of a trial, from its registered enrollment, or from its endpoint definition. Nor can the reported adverse-event counts answer the efficacy question. This record therefore demonstrates why interpretation must begin with whether an analyzable result is actually reported.
It also highlights the role of denominators and analysis populations. The registry gives at-risk counts for adverse-event summaries, but it does not report the population assessed for the primary endpoint. Without group-specific efficacy counts and denominators, no responder comparison can be reconstructed. Without a reported uncertainty measure, precision cannot be assessed even if the endpoint itself is well defined.
Finally, planning calculations and trial results answer different questions. In general, planning illustrations rely on assumptions about an effect and a design; they are not observed evidence and are not observed power. Keeping that distinction clear prevents a planning scenario from being mistaken for a finding. The record's main statistical contribution is thus to document the intended comparison and endpoint, while its early termination and lack of formal analysis leave the comparative question unanswered.
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.
Several trial-specific limitations follow directly from the registry entry. The study status is TERMINATED, and the primary endpoint description states that the sponsor's early termination meant no formal analyses were conducted. As a result, the registry record does not report responder counts, a comparison between groups, or an effect estimate with a measure of uncertainty. This prevents assessment of both the direction and precision of the planned efficacy comparison.
The registry enrollment is 21, but arm-specific enrollment and participant flow are not reported in the registry record. It is not possible to determine from this entry how many participants were randomized, received study intervention, completed maintenance, or had evaluable seizure diaries. The adverse-event at-risk counts are limited and are not a substitute for an efficacy analysis population.
The endpoint relies on seizure diaries. The record describes how diaries were intended to be maintained but does not report diary completeness, rules for deriving frequency when records were incomplete, or methods for handling missing observations. It also does not report the statistical analysis plan, analysis population, or specific test or model. The reason for early termination is not reported in the registry record beyond attribution to the sponsor.
The safety entries do not include event terms for serious adverse events, and death counts are not reported in the registry record. The other adverse-event counts are descriptive and do not provide a detailed event profile or a formal comparison. Together, these limitations mean that the registry supports a description of the planned trial and a small amount of safety information, but not a formal assessment of efficacy or a comprehensive evaluation of safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures — NCT00692003.
- Registry record last updated 2017-03-14; status last verified 2017-02.
- Results first posted 2012-10-12.
- 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
This Phase 3 study was randomized, double-blind, parallel-group and described as multicentre. It compared adjunctive zonisamide with placebo for primary generalised tonic-clonic seizures. The registry lists enrollment as 21, a start date of 2008-08-01, primary completion in 2008-11, and status TERMINATED.
The primary endpoint was the number of participants meeting a responder definition during maintenance: a decrease of at least 50% in seizure frequency relative to baseline. The record says the sponsor terminated the study early and no formal analyses were conducted. It therefore does not report an analyzed efficacy comparison. The posted safety counts are limited, and death counts are not reported in the registry record.