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 Study to Assess the Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures (CATZ Extension Study) (NCT01136954), a na phase 3 study. The primary outcome is Treatment Emergent Non-Serious Adverse Events With Greater Than 5% Frequency.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01136954 |
| Phase | Phase 3 |
| Condition | Partial Seizures |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 144 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eisai Limited |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns pediatric participants with partial seizures who were treated with one or two other anti-epileptic drugs. The registry’s safety population includes subjects who entered the study and received at least one dose of study drug. The registry record does not provide further age details or a breakdown of who completed the extension.
Intervention
Zonisamide was used as an adjunctive treatment during an open-label extension. The stated purpose was to assess long-term safety and efficacy when zonisamide was added to existing anti-epileptic drug treatment. The duration recorded for the primary safety endpoint is Week 1 through Week 59.
Comparator
There was no randomized comparator during the extension. The two adverse-event groups are labelled according to whether participants received placebo or zonisamide during the core study; both groups are labelled as receiving zonisamide in the extension. These groups are not a like-for-like control comparison.
Primary question
The primary endpoint concerns treatment-emergent non-serious adverse events with greater than 5% frequency. It counts participants experiencing an event, rather than repeated episodes in the same participant. Although the registry identifies this endpoint, its analyzed result is not reported in the registry record. Seizure-frequency outcomes are listed as secondary outcomes, but their analyzed results are also not reported in the registry record.
3. Trial Design
This is a Phase 3, open-label extension study, described as following a double-blind, randomized, placebo-controlled, multi-centre core study. The extension itself is recorded as a single-group study with no masking and no allocation. Its intervention is zonisamide. Enrollment is recorded as 144, and the study status is completed. The recorded study dates are 2008-07 for study start and 2012-01 for primary completion.
The distinction between the core study and the extension is important. The extension’s group labels distinguish participants by the treatment they received during the core study: zonisamide or placebo. In the extension, both labels include zonisamide. The registry’s own caution is that this is not a randomized comparison and the groups are not a like-for-like control comparison. Their adverse-event counts should therefore be read as descriptive information about the listed groups, not as a randomized estimate of a treatment contrast.
The stated purpose is to assess long-term safety and efficacy of adjunctive zonisamide in pediatric subjects receiving one or two other anti-epileptic drugs. The registry does not report the extension’s detailed visit schedule, dose regimen, eligibility criteria, or the number of participants who completed follow-up. Such details are not reported in the registry record. The primary endpoint’s timeframe is Week 1 through Week 59, but that alone does not establish how long each participant was observed.
The record describes a safety population consisting of all subjects who entered the study and received at least one dose of study drug. The analyzed population for seizure-frequency outcomes, and any other analysis populations, are not reported in the registry record. The record does not state a sample-size justification or the extension’s planned statistical analysis methods.
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.
Overall Study
| Stage | Zonisamide(Placebo During Core Study) | Zonisamide (Zonisamide During Core Study) |
|---|---|---|
| STARTED | 72 | 72 |
| COMPLETED | 48 | 51 |
| NOT COMPLETED | 24 | 21 |
Reasons for not completing this period:
| Reason | Zonisamide(Placebo During Core Study) | Zonisamide (Zonisamide During Core Study) |
|---|---|---|
| Adverse Event | 3 | 2 |
| Withdrawal by Subject | 6 | 2 |
| Lack of Efficacy | 14 | 13 |
| Physician Decision | 0 | 1 |
| Other | 1 | 3 |
Analysis population for the primary outcome, as defined in the registry: Safety Population (all subjects who entered the study and received at least one dose of study drug)
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 During Core Study) | Zonisamide (Zonisamide During Core Study) | Total |
|---|---|---|---|---|
| Participants analysed | 72 | 72 | 144 | |
| Age, Customized: 6-11 Years | Participants | 34 | 33 | 67 |
| Age, Customized: 12-18 Years | Participants | 38 | 39 | 77 |
| Sex: Female, Male: Female | Participants | 32 | 41 | 73 |
| Sex: Female, Male: Male | Participants | 40 | 31 | 71 |
6. Primary Endpoint
The registry lists the primary outcome as Treatment Emergent Non-Serious Adverse Events With Greater Than 5% Frequency, measured over Week 1 through Week 59.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled “Treatment Emergent Non-Serious Adverse Events With Greater Than 5% Frequency.” Its unit is participants, and the registry describes the outcome as a number. The timeframe is Week 1 through Week 59. A treatment-emergent adverse event is defined as an adverse event starting on or after Day 1 and within 15 days of the last dose. For each event, a participant is counted once even if that participant experienced multiple episodes.
This participant-based approach is useful for describing how many people experienced an event, without allowing repeated episodes in one person to inflate the participant count. The endpoint focuses on non-serious events meeting the stated frequency criterion; it is not a count of every event episode. In general, an adverse-event endpoint is used to characterize safety during the period under observation, but a count by itself does not establish that study treatment caused an event.
The registry record identifies the endpoint but does not report its analyzed result. It therefore does not establish how many participants met this primary endpoint or provide an estimate of its uncertainty. Serious adverse events are presented separately in the posted results and should not be treated as the primary non-serious endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed extension study with 144 enrolled participants and a primary endpoint focused on treatment-emergent non-serious adverse events. It also lists seizure-frequency outcomes as secondary measures. However, it reports no analyses for these outcomes. The primary endpoint’s result, including a participant count for non-serious events meeting the stated frequency criterion, is not reported in the registry record. The seizure-frequency results are likewise not reported in the registry record. Consequently, the posted information does not support a quantitative conclusion about the primary endpoint or the listed efficacy outcomes.
The available adverse-event counts are descriptive. In the group labelled “Zonisamide(Placebo During Core Study),” 3 participants are listed with serious adverse events and 18 with other adverse events, with 72 at risk for each listing. In the group labelled “Zonisamide (Zonisamide During Core Study),” 7 participants are listed with serious adverse events and 25 with other adverse events, again with 72 at risk for each listing. These counts do not constitute a randomized comparison: the groups are distinguished by core-study treatment, while both are labelled as receiving zonisamide in the extension. The record explicitly cautions that the groups are not a like-for-like control comparison.
The serious-event terms listed include bronchitis, lymph gland infection, pneumonia, urinary tract infection, viral infection, and partial seizures with secondary generalisation. Each is accompanied by 1.4%. The registry does not give a group attribution for those terms in the listed information, so they should not be assigned to either extension group from these details alone. Deaths are not reported in the registry record.
General statistical interpretation: counts describe observed participants in the recorded groups. Without a reported analysis, uncertainty estimates, or an appropriate randomized contrast, the counts do not quantify a causal difference between treatments. A confidence interval, when reported, expresses the precision of an estimate under its statistical assumptions; none is reported for the primary endpoint in the registry record. The absence of reported analyses also means the degree of precision for the seizure-frequency outcomes cannot be assessed.
The group counts should not be converted into a treatment effect by comparing them directly. Participants entered the extension with different core-study treatment histories, and the record does not describe a randomized assignment to extension groups. It also does not report adjustments for baseline differences, exposure time, or other potential differences between groups. These missing details matter because the duration and circumstances of observation can influence adverse-event counts. The available figures are best read as counts recorded for the two labelled groups, not as evidence that one core-study history led to a higher or lower risk in the extension.
9. Statistical Methods Explained
What does a participant count represent?
The primary endpoint uses participants as its unit. For an adverse event, this means the count represents people who experienced that event under the endpoint definition, rather than the total number of episodes. The registry explicitly states that each participant is counted once for each event even if multiple episodes occur. This distinction matters: a participant with repeated episodes may contribute once to a participant count for that event, while an episode-based measure would record each episode separately. The posted serious and other adverse-event figures are also counts of affected participants in the respective groups.
The title of the primary endpoint restricts it to non-serious adverse events with greater than 5% frequency. It should not be confused with the serious adverse-event counts listed separately. The registry defines a treatment-emergent event by its timing: it must start on or after Day 1 and within 15 days of the last dose. This definition identifies events within a specified treatment-related observation window; it does not by itself prove that treatment caused the event.
What can a single-group extension establish?
The extension is recorded as a single-group, open-label study with no masking and no allocation. General statistical principle: an open-label study does not conceal treatment assignment from participants or study personnel, while a randomized controlled comparison uses random assignment to create groups intended to be comparable at baseline. The extension record does not describe randomized assignment to the two groups shown in the adverse-event results. Those labels refer to prior core-study treatment, and both groups are described as receiving zonisamide in the extension. Therefore, the group counts are descriptive rather than a randomized estimate of the effect of zonisamide versus a control during the extension.
General statistical principle: when groups differ in treatment history or other characteristics, their outcomes can differ for reasons other than the treatment being studied. A direct numerical contrast between their counts would not address such differences. The registry’s warning that the arms are not a like-for-like control comparison is therefore central to interpretation. No adjusted comparison or model-based estimate is reported in the registry record.
How should the seizure-frequency outcomes be read?
The secondary outcomes include the percentage of participants with a decrease from baseline in 28-day seizure frequency of =50%(Responder), the median change from Study 312 baseline in 28-day seizure frequency, and the median percent change from Study 312 baseline. These are distinct summaries: one describes a responder category, while the other listed measures describe changes in seizure frequency. The registry record does not report analyzed values for them. It also does not report how baseline values, missing observations, or repeated measurements were handled.
General statistical principle: a median describes the middle of an ordered set of observations and can be useful when data are skewed or contain extreme values. A responder outcome turns a continuous change into a category defined by a threshold, which can be easier to interpret but discards information about the size of changes within each category. These concepts explain the kinds of measures named in the registry; they do not establish any result for this study.
What do significance levels and planning calculations mean?
General statistical principle: a significance level is a prespecified rule for judging how unusual data would be under a stated null hypothesis. A two-sided test allows evidence in either direction. The record’s planning-assumption description refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation for planning illustrations. Those assumptions are described as planning illustrations based on an observed effect, not as the study’s own design. The registry record does not report a sample-size justification for the trial or analyses of the primary endpoint.
Planning calculations are not observed power. They ask how many participants might be needed under specified assumptions to detect an effect of a chosen size. The record describes the effect to detect as a stated fraction of an observed effect, but the analyzed primary effect is not reported in the registry record. A planning illustration cannot replace the missing trial result, and it does not show that the study had a particular probability of detecting an effect after the fact.
General statistical principle: over-dispersion occurs when variation in count data exceeds what a simple probability model assumes. It can make standard errors too small if ignored. The registry record does not report a count model or an over-dispersion assessment for this study, so no such method should be attributed to its analysis.
Why do analysis populations and missing-data methods matter?
The stated safety population includes all subjects who entered the study and received at least one dose. This definition clarifies who contributes to the safety description, but it does not specify the population used for efficacy outcomes. Nor does the registry record explain how participants with incomplete follow-up or missing seizure diaries were handled. General statistical principle: missing observations can affect an estimate when the participants with available data differ systematically from those without data. Without a reported method and counts of missing observations, the consequences cannot be assessed from the registry record.
The record lists four outcome measures and reports zero analyses. It does not give a multiplicity strategy, such as a prespecified hierarchy or adjustment for testing multiple outcomes. General statistical principle: examining multiple outcomes can increase the chance of finding an apparently notable result by chance if each is interpreted independently. Whether and how that issue was addressed is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures, including the primary safety endpoint and three secondary seizure-frequency outcomes. It reports no analyses. A plan for handling multiple outcomes or multiple statistical tests is not reported in the registry record. General statistical principle: when several outcomes or hypotheses are examined, the chance of an apparently notable result by chance can increase if each is assessed separately. Methods such as a prespecified testing hierarchy or multiplicity adjustment can address that concern, but the record does not state whether either was used.
The safety population is defined as all subjects who entered the study and received at least one dose of study drug. The record does not report the analysis population for efficacy outcomes, numbers with missing outcome data, reasons for missingness, or a method for handling missing observations. These omissions prevent assessment of how incomplete follow-up may have affected the posted results. The number enrolled does not by itself establish how many contributed data to every endpoint.
The registry record does not report the statistical analysis plan, interim analyses, or a sample-size justification. The planning assumptions described in the record are illustrations rather than the trial’s own design. Consequently, the available information does not establish which analyses were prespecified, whether analyses changed, or how the study’s intended precision was determined.
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 |
|---|---|---|---|
| Zonisamide(Placebo During Core Study) | 3 | 72 | 4.2% |
| Zonisamide (Zonisamide During Core Study) | 7 | 72 | 9.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Zonisamide(Placebo During Core Study) | 18 of 72 |
| Zonisamide (Zonisamide During Core Study) | 25 of 72 |
Most frequent serious adverse event terms
| Event term | Organ system | Zonisamide(Placebo During Core Study) | Zonisamide (Zonisamide During Core Study) |
|---|---|---|---|
| Bronchitis | Infections and infestations | 0 of 72 | 1 of 72 |
| Lymph gland infection | Infections and infestations | 1 of 72 | 0 of 72 |
| Pneumonia | Infections and infestations | 1 of 72 | 0 of 72 |
| Urinary tract infection | Infections and infestations | 1 of 72 | 0 of 72 |
| Viral infection | Infections and infestations | 0 of 72 | 1 of 72 |
| Partial seizures with secondary generalisation | Nervous system disorders | 0 of 72 | 1 of 72 |
| Status epilepticus | Nervous system disorders | 0 of 72 | 1 of 72 |
| Ventricular extrasystoles | Cardiac disorders | 0 of 72 | 1 of 72 |
| Abdominal pain | Gastrointestinal disorders | 1 of 72 | 0 of 72 |
| Foot fracture | Injury, poisoning and procedural complications | 0 of 72 | 1 of 72 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Zonisamide(Placebo During Core Study) | Zonisamide (Zonisamide During Core Study) |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 6 of 72 | 9 of 72 |
| Weight decreased | Investigations | 6 of 72 | 6 of 72 |
| Headache | Nervous system disorders | 4 of 72 | 7 of 72 |
| Decreased Appetite | Metabolism and nutrition disorders | 5 of 72 | 4 of 72 |
| Bronchitis | Infections and infestations | 4 of 72 | 3 of 72 |
| Respiratory tract infection | Infections and infestations | 2 of 72 | 4 of 72 |
| Abdominal pain | Gastrointestinal disorders | 1 of 72 | 4 of 72 |
Serious events with the highest arm-level rate: bronchitis (1.4%), lymph gland infection (1.4%), pneumonia (1.4%), urinary tract infection (1.4%), viral infection (1.4%).
For the group labelled “Zonisamide(Placebo During Core Study),” the record lists 3 participants with serious adverse events and 18 with other adverse events; each listing has 72 at risk. For “Zonisamide (Zonisamide During Core Study),” it lists 7 participants with serious adverse events and 25 with other adverse events, also with 72 at risk for each listing. These are participant counts, not event-episode totals.
The group labels refer to treatment during the core study; both groups are labelled as receiving zonisamide in the extension. The registry explicitly notes that this is not a randomized comparison and the groups are not a like-for-like control comparison. The counts should therefore be read descriptively, not as evidence of a treatment-related difference. Serious-event terms listed include bronchitis, lymph gland infection, pneumonia, urinary tract infection, viral infection, and partial seizures with secondary generalisation, each at 1.4%. The record does not attribute these terms to a specific group in the listed information. Deaths are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted results describe an open-label extension in which zonisamide was used as adjunctive treatment and provide counts of participants with serious and other adverse events in groups defined by treatment during the core study. They also identify a primary endpoint for non-serious treatment-emergent events and list seizure-frequency outcomes. However, the analyzed result for the primary endpoint and the results for the secondary seizure-frequency outcomes are not reported in the registry record. The available record therefore does not show the size or precision of an estimated effect on those endpoints.
The adverse-event counts do not establish a causal treatment effect. Both extension groups are labelled as receiving zonisamide, and the groups are distinguished by prior core-study treatment. The registry specifically cautions that they are not a like-for-like control comparison. Differences in these descriptive counts cannot be interpreted as a randomized comparison of zonisamide with placebo during the extension.
General statistical principle: a study result is most informative when an estimate is accompanied by an uncertainty measure and interpreted in light of the design, endpoint definition, analysis population, and missing data. Those elements are not all reported for the primary and efficacy outcomes in this record. Counts alone do not reveal how precisely an underlying event frequency or treatment contrast has been estimated.
These findings should not be taken to establish that zonisamide does or does not change seizure frequency, or that it causes or prevents an adverse event. The record’s stated purpose is to assess long-term safety and efficacy, but the purpose of a study is not itself a result. The appropriate reading is limited to the design information and the descriptive safety counts that are actually posted, alongside the absence of reported analyses for the named primary and secondary outcomes.
13. Why This Trial Matters Statistically
This study raises several important statistical distinctions for readers of clinical trial records. First, an extension study can provide additional descriptive information about participants who continue into follow-up, but a single-group, open-label extension does not automatically preserve the randomized comparison of its core study. Here, the adverse-event groups are labelled by core-study treatment, while both are described as receiving zonisamide during the extension. The registry explicitly states that these are not like-for-like control groups.
Second, endpoint definitions shape what a reported count means. The primary endpoint is participant-based, limited to treatment-emergent non-serious adverse events with greater than 5% frequency, and uses a timing window that extends through 15 days after the last dose. Counting a participant once for each event avoids counting repeated episodes as additional people. These design details are essential for interpreting any eventual result, but the endpoint’s analyzed result is not reported in the registry record.
Third, a stated study purpose and a completed status do not substitute for outcome analyses. The registry lists seizure-frequency outcomes but does not report their analyzed values, uncertainty, or handling of missing data. This prevents readers from evaluating the magnitude and precision of any efficacy finding from the posted record. Similarly, adverse-event counts are useful descriptive information, but they do not alone provide a causal comparison.
More broadly, this record illustrates why interpretation should consider the study structure, analysis population, outcome definition, missing data, and multiplicity alongside counts. Information not reported in the registry record limits what can be concluded, even when the study’s objectives and some safety counts are available.
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 main limitation for interpreting results is that the registry record reports no analyses. The primary non-serious adverse-event endpoint is identified, but its analyzed result is not reported in the registry record. The seizure-frequency measures are listed as secondary outcomes, but their results are also not reported. No estimates of uncertainty for these outcomes are reported, so their precision cannot be assessed.
The study is recorded as an open-label, single-group extension with no allocation or masking. The adverse-event groups reflect core-study treatment history, not randomized assignment during the extension. The record itself cautions that the groups are not a like-for-like control comparison. It does not report an adjusted comparison, participant-level baseline information, or exposure-time information that could support a more controlled interpretation of group counts.
The registry defines the safety population, but does not report the efficacy analysis population, the number completing follow-up, missing-data counts, or missing-data methods. The statistical analysis plan, sample-size justification, and interim-analysis information are not reported in the registry record. A plan for handling multiple outcomes is also not reported. These omissions limit assessment of whether the reported outcomes were analyzed as intended and how robust any findings might be.
The primary endpoint concerns non-serious events meeting a frequency criterion, while the posted safety counts separately describe serious and other adverse events. The record does not provide enough detail in the listed information to map every adverse-event count to the primary endpoint definition. The listed serious-event terms are not assigned to a particular extension group. Deaths are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Assess the Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures (CATZ Extension Study) — NCT01136954.
- Registry record last updated 2016-01-25; status last verified 2015-11.
- Results first posted 2013-02-06.
- 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
NCT01136954 is a completed Phase 3, open-label extension study of adjunctive zonisamide for pediatric partial seizures. It followed a double-blind, randomized, placebo-controlled core study, but the extension is recorded as single-group, with no allocation and no masking. Enrollment was 144. The recorded study start is 2008-07, and primary completion is 2012-01.
The primary endpoint is treatment-emergent non-serious adverse events with greater than 5% frequency, measured as participants from Week 1 through Week 59. Three secondary outcomes concern seizure-frequency changes or responder status. Analyses of the primary and secondary outcomes are not reported in the registry record. Descriptive safety counts are listed for two groups defined by core-study treatment; both groups are labelled as receiving zonisamide during the extension, and the registry cautions that they are not a like-for-like control comparison.