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 Follow up Trial for Keppra (Levetiracetam) as Monotherapy in Patients With Newly Diagnosed Epilepsy Coming From N01175 (NCT00175903). (NCT00291655), a non-randomized phase 3 study. The primary outcome is Assessment of Safety of Levetiracetam as Per Adverse Event (AE) Reporting in Open-label Therapy Phase.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00291655 |
| Phase | Phase 3 |
| Condition | Epilepsy |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 130 |
| Arms in the primary outcome | n/a |
| Lead sponsor | UCB Pharma |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned adult participants with newly diagnosed epilepsy who had completed the therapeutic confirmatory, open-label N01175 trial and who benefited from levetiracetam monotherapy. The brief summary describes eligibility as adults “≥16 or 18 years,” so the exact age threshold is not clear from the registry record. The safety population was defined as participants treated at least once. Enrollment was 130.
Intervention
The intervention was levetiracetam, also identified in the arm description as LEV. The stated purpose was to offer continued treatment while assessing long-term safety, including adverse events and changes in body weight. The record describes an open-label therapy phase with an 18-month timeframe.
Comparator
There was no randomized comparator group. The design is identified as non-randomized and single-group, with no masking. Consequently, the record does not present a like-for-like control comparison. It cannot separate changes associated with continued treatment from changes over time or other influences.
Primary question
The primary question was descriptive: what adverse events were reported during open-label levetiracetam therapy among participants in the safety population? The registry lists counts of participants with adverse events, including serious and drug-related events, as categories to be summarized. It does not report an estimate of comparative treatment effect. The secondary outcome concerned change from baseline in body weight to withdrawal or the end of study after 18 months.
3. Trial Design
This was a phase 3, multicenter, open-label follow-up study of levetiracetam in epilepsy. The registry classifies it as non-randomized, with no masking and a single-group model. Enrollment was 130. The study status is completed; the recorded start is 2006-06 and primary completion is 2008-04.
Participants came from N01175, a therapeutic confirmatory, open-label trial of levetiracetam monotherapy. The brief summary says the follow-up offered participants who completed that study and benefited from treatment an opportunity to continue levetiracetam. This makes the study population a selected group of prior-trial completers, rather than a newly assembled sample of all people with epilepsy. The exact process for selecting or inviting participants is not reported in the registry record.
The stated goal was continued assessment of safety through adverse-event reporting and observation of weight changes. The primary outcome concerned adverse-event reporting during the open-label therapy phase, with a stated timeframe of 18 months. The secondary outcome was change from baseline in body weight to withdrawal or end of study after 18 months. The registry identifies levetiracetam as the intervention and gives no separate treatment arm for comparison.
An open-label, single-group follow-up can describe events occurring among those treated, but its design does not provide a randomized estimate of what would have happened under a different treatment or without continued treatment. Non-randomized allocation also means that any comparison with external information would not automatically be like-for-like. The registry record does not report a protocol-level explanation of the design choices, a planned sample-size justification, or details of any interim 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.
Overall Study
| Stage | Levetiracetam Open- Label Treatment |
|---|---|
| STARTED | 130 |
| COMPLETED | 115 |
| NOT COMPLETED | 15 |
Analysis population for the primary outcome, as defined in the registry: Safety population that includes all subjects that have been treated once.
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 | Levetiracetam Open- Label Treatment |
|---|---|---|
| Participants analysed | 130 | |
| Age, Continuous | years | 40.68 (SD 18.35) |
| Sex: Female, Male: Female | Participants | 58 |
| Sex: Female, Male: Male | Participants | 72 |
| Region of Enrollment: France | participants | 18 |
| Region of Enrollment: Finland | participants | 9 |
| Region of Enrollment: Poland | participants | 32 |
| Region of Enrollment: Belgium | participants | 25 |
| Region of Enrollment: Bulgaria | participants | 31 |
| Region of Enrollment: Switzerland | participants | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Assessment of Safety of Levetiracetam as Per Adverse Event (AE) Reporting in Open-label Therapy Phase, measured over during open-label therapy phase of 18 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was an assessment of levetiracetam safety through adverse-event reporting during the open-label therapy phase. Its stated timeframe was during the therapy phase of 18 months. The endpoint was expressed as the number of participants, and the description says that summaries were provided for occurrences such as any adverse event and drug-related adverse events. The listed safety population includes all participants who had been treated at least once.
Counting participants with reported events is a descriptive way to characterize what was observed in a treated group. It can communicate the number of participants recorded in an event category, but a count alone does not establish that treatment caused an event. Nor does a single-group count estimate how often the same events would have occurred under a different treatment or in the absence of treatment. Those questions require an appropriate comparison and a defined analysis.
The record also identifies change from baseline in body weight to withdrawal or end of study after 18 months as a secondary outcome. The registry record does not report a numerical result for that outcome in the registry record for this account. The primary endpoint description refers to categories of adverse events but does not provide details of the event-coding rules, the approach to repeated events, or the handling of participants who withdrew before the end of the stated timeframe.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety figures describe counts in the levetiracetam open-label treatment group. The record gives 130 participants at risk for serious adverse events and 6 affected, and 130 at risk for other adverse events and 10 affected. These are descriptive counts, not results from a comparison between treatment groups. The record also lists six serious-event terms, each reported as 0.8%: Acute coronary syndrome, Hepatic cirrhosis, Skin laceration, Grand mal convulsion, Alcoholism, and Tonsillitis.
The named terms should be read as reported categories, not as a complete account of every aspect of the safety experience. A term-specific percentage does not show whether the event was judged related to treatment, how severity was defined, whether participants had more than one event, or whether the terms represent repeated events in the same participant. Those details are not reported in the registry record. The primary outcome description indicates that categories included any adverse event and drug-related adverse events, but the registry entries do not include a numerical result for every such category.
These data do not establish a comparative risk. Since the design was single-group and non-randomized, there is no concurrent randomized control group against which to interpret the counts. In general, adverse events observed during treatment may reflect underlying illness, background occurrence, other exposures, treatment, or a combination of factors. An uncontrolled count cannot distinguish among these explanations. The selected population—participants who completed the earlier trial and benefited from treatment—also limits how broadly the observed experience can be applied.
The registry record reports no analyses, and no confidence interval, hypothesis test, or adjusted estimate is included in the registry record. A confidence interval, in general, describes the uncertainty around an estimate under specified assumptions; without a reported interval or sufficient analysis details, the precision of these safety counts cannot be assessed from the record. The counts remain useful as a description of reported events in this cohort, but they do not quantify a treatment effect or show whether the event frequency differs from another setting.
The record’s listed deaths field has no reported value. That is not evidence of zero deaths; mortality information is not reported in the registry record. Similarly, the absence of a numerical body-weight result in the registry entries should not be interpreted as no change. The registry identifies body-weight change as a secondary outcome, but the result itself is not reported in the registry record.
9. Statistical Methods Explained
Understanding the statistical meaning of this study begins with its design. The registry identifies a non-randomized, single-group, open-label follow-up. Participants received levetiracetam, and no concurrent randomized comparator is described. The primary outcome is a count-based safety summary: participants with reported adverse events. This kind of descriptive endpoint answers what was recorded in the treated group; it does not by itself estimate the effect of treatment relative to an alternative.
What does a participant count represent?
A participant count records how many people in the defined analysis population were classified in an outcome category. The registry defines the safety population as all participants treated at least once. For the posted serious-event summary, 130 were at risk and 6 were affected; for other adverse events, 130 were at risk and 10 were affected. These counts depend on how the event categories and analysis population were defined. The record does not give detailed rules for event coding, duplicate reports, or how multiple events in a participant were handled.
Participant counts and event counts are not interchangeable. A person may experience more than one event, and the registry’s endpoint is framed in terms of participants with events. The listed serious-event terms and their percentages add detail about reported categories, but do not establish the number of distinct people represented across all terms. No total across terms should be inferred from those entries. The available information also does not establish whether a participant could appear in more than one category.
Why does the design matter?
Random allocation is a method for making treatment groups comparable, on average, with respect to measured and unmeasured factors. This study is classified as non-randomized and single-group, so it has no randomized between-group contrast. As a general statistical point, an event count in a treated group can describe experience during treatment, but cannot isolate a treatment-associated difference without a suitable comparison. Changes over time, characteristics of participants, and other influences may contribute to what is observed.
The open-label nature of the study means treatment was not masked. In general, knowledge of treatment can affect reporting, assessment, and decisions about care or withdrawal. The registry record does not provide enough detail to determine how these possibilities were addressed. The population also came from people who completed the earlier N01175 trial and benefited from treatment, which is relevant to interpretation: their experience may not represent people who did not complete that study or did not benefit.
What would uncertainty measures add?
A confidence interval is a general statistical tool for expressing uncertainty around an estimated quantity. Its width reflects both the observed data and the assumptions of the analysis. A count or proportion without an interval gives limited information about precision, particularly when the event is uncommon. The registry entries do not report confidence intervals or other uncertainty measures for the safety counts. No interval should therefore be inferred from the posted figures.
Hypothesis tests and p-values address a specified statistical question under a stated model. They do not establish causation, and their interpretation depends on the design, endpoint, and analysis plan. The registry record reports 0 analyses and does not give a test result for the primary endpoint. It would be inappropriate to infer a test, statistical significance, or an adjusted effect from the descriptive counts alone.
How should event percentages be read?
The serious-event terms are each listed with a percentage of 0.8%. Those values are registry entries for named terms; they are not comparative estimates. The record does not explain whether the percentages refer to participants, events, or another calculation convention, nor does it provide a term-specific uncertainty interval. The percentages should therefore be read as reported figures, without reverse-engineering counts or assuming a denominator beyond the information explicitly stated.
Over-dispersion is a general issue in count data: observed variation can be greater than a simple statistical model expects, for example when event occurrence varies substantially between participants or when participants can have multiple events. A model that ignores such variation can understate uncertainty. This study’s primary summary is described as a number of participants, and the registry entries do not describe a model for event counts or a method accounting for over-dispersion. It is thus not possible to evaluate whether such modeling was considered.
What can the planning assumptions tell readers?
In general, a sample-size planning illustration estimates the number of participants that might be needed to detect a specified effect under stated assumptions. It is a design aid, not evidence about the result of the completed study, and it is not observed power. The record’s general planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. However, this trial is single-group, and the registry entries do not report a comparative effect estimate or an analysis from which such a planning illustration can be interpreted for this study. No sample-size justification for the trial itself is reported in the registry record.
The registry lists an 18-month timeframe for the primary safety outcome and identifies weight change through withdrawal or end of study after 18 months as secondary. A stated timeframe helps define the period relevant to outcome collection, but it does not establish that every participant was observed for the full period. Withdrawal, incomplete reporting, and differing follow-up can affect descriptive summaries. The record does not describe how these issues were handled statistically.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary safety outcome and a secondary outcome concerning change from baseline in body weight to withdrawal or end of study after 18 months. It also lists two outcome measures and reports 0 analyses. The registry entries do not describe a statistical analysis plan, a hierarchy among adverse-event categories, or adjustments for evaluating multiple outcomes or categories. Whether multiplicity was addressed is therefore not reported in the registry record.
Multiplicity is a general concern when many outcomes, event types, timepoints, or subgroup comparisons are examined. The more opportunities there are to identify an apparently unusual result, the more important it is to distinguish prespecified analyses from exploratory ones and to explain any adjustment strategy. The listed serious-event terms are descriptive entries; they should not be treated as independently tested findings because no tests are reported.
Missing-data methods are also not described. The safety population includes all participants treated at least once, but the record does not state how participants with incomplete follow-up, missing event information, or early withdrawal contributed to each summary. The secondary outcome’s timeframe explicitly allows follow-up to withdrawal or end of study, but the method for handling missing weight measurements is not reported in the registry record. In general, missingness can affect interpretation when the reason data are absent is associated with health status, treatment experience, or the outcome itself.
The registry does not report an intention-to-treat analysis population or other analysis-population definitions beyond the safety population. It is therefore not possible to assess whether the outcome summaries used a population different from the stated safety set, or whether participants were excluded from particular analyses. These omissions limit assessment of the analysis process, but do not change the descriptive nature of the posted safety counts.
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 |
|---|---|---|---|
| Levetiracetam Open- Label Treatment | 6 | 130 | 4.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Levetiracetam Open- Label Treatment | 10 of 130 |
Most frequent serious adverse event terms
| Event term | Organ system | Levetiracetam Open- Label Treatment |
|---|---|---|
| Acute coronary syndrome | Cardiac disorders | 1 of 130 |
| Hepatic cirrhosis | Hepatobiliary disorders | 1 of 130 |
| Skin laceration | Injury, poisoning and procedural complications | 1 of 130 |
| Grand mal convulsion | Nervous system disorders | 1 of 130 |
| Alcoholism | Psychiatric disorders | 1 of 130 |
| Tonsillitis | Infections and infestations | 1 of 130 |
| Foot fracture | Injury, poisoning and procedural complications | 1 of 130 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Levetiracetam Open- Label Treatment |
|---|---|---|
| Weight increased | Investigations | 7 of 130 |
| Weight decreased | Investigations | 3 of 130 |
Serious events with the highest arm-level rate: acute coronary syndrome (0.8%), hepatic cirrhosis (0.8%), skin laceration (0.8%), grand mal convulsion (0.8%), alcoholism (0.8%).
The registry reports 6 participants affected by serious adverse events among 130 at risk, and 10 affected by other adverse events among 130 at risk, in the levetiracetam open-label treatment group. These are category counts, not a comparison with an untreated or alternative-treatment group. They describe what the record classified in the treated cohort.
Six serious-event terms are listed, each with a reported value of 0.8%: Acute coronary syndrome, Hepatic cirrhosis, Skin laceration, Grand mal convulsion, Alcoholism, and Tonsillitis. The record does not state whether the listed terms were considered related to levetiracetam, whether they occurred in separate participants, or whether any participant had multiple terms. The terms should not be added together or treated as a count of distinct participants.
The deaths field has no reported value. It should not be read as a zero count. The record also does not give uncertainty intervals or detailed information on how serious events were defined and coded. In general, safety counts are most informative when interpreted alongside event definitions, follow-up completeness, attribution rules, and an appropriate comparison. Those details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The result information supports a limited, descriptive conclusion: the registry records adverse-event counts and named serious-event terms among participants receiving open-label levetiracetam in a single-group follow-up. The primary purpose was safety assessment through adverse-event reporting, and the record gives a defined safety population of participants treated at least once. It does not provide a randomized comparison or a reported statistical analysis of treatment effect.
That distinction matters. An event occurring during treatment is not, by timing alone, proof that treatment caused it. Without a comparable control group and a prespecified comparative analysis, the observed counts cannot show whether the events were more or less frequent than they would have been under another condition. Nor do they establish a causal explanation for any individual event. The listed terms and percentages are registry descriptions, not evidence of a treatment-related mechanism.
The study’s participants had completed the earlier N01175 trial and were described as having benefited from levetiracetam. This selected follow-up group may differ from people who did not complete the earlier trial or did not benefit. The findings should therefore be interpreted in the context of that population, rather than assumed to represent every person with epilepsy or every setting of levetiracetam use.
The record identifies body-weight change as a secondary outcome but does not report a numerical result for it in the registry entries. The absence of that result cannot be interpreted as no change. Likewise, a blank deaths field does not establish that no deaths occurred. The registry record does not report the relevant information.
Overall, the posted data describe safety events recorded in the study cohort. They do not establish comparative safety, treatment efficacy, or a causal relationship between levetiracetam and any event. The precision and completeness of the event estimates also cannot be judged fully because uncertainty measures and detailed follow-up and missing-data methods are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates the value and limits of a follow-up safety cohort. Continuing observation after a therapeutic trial can document adverse events during longer-term treatment in people who entered the follow-up. The registry’s primary outcome is explicitly safety-focused, and its event counts offer a direct description of what was recorded in the treated group.
Statistically, the design determines what those counts can answer. A single-group, non-randomized study can characterize events in its participants, but it does not create a randomized counterfactual. Without a concurrent comparator, differences attributable to treatment cannot be separated from background occurrence, participant characteristics, or changes over time. The open-label design also makes transparent reporting of event definitions and ascertainment methods especially relevant, yet those details are not reported in the registry record.
The study also highlights the importance of defining the analysis population. The registry specifies a safety population consisting of everyone treated at least once, while the cohort itself came from participants who completed N01175 and benefited from treatment. These descriptions clarify who the findings concern, while also identifying a selected population that may not represent other patients.
Finally, descriptive counts are not a substitute for uncertainty estimates or a prespecified analysis. The registry reports no analyses, and the available information does not include confidence intervals, comparative estimates, or detailed missing-data methods. Readers can use the recorded counts as a summary of reported events, while recognizing that the record does not establish comparative risk or explain how completely outcomes were captured. The statistical importance lies in matching the conclusion to the design and the information actually reported.
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 central limitation is the absence of a randomized comparator. The study is classified as non-randomized and single-group, so the reported adverse-event counts cannot quantify a difference between levetiracetam and another treatment or no treatment. The open-label design further means that the record does not establish blinded event assessment.
The follow-up population was selected from participants who completed N01175 and benefited from treatment. This limits generalizability to people who did not complete that earlier study or did not benefit. The brief summary describes adults as “≥16 or 18 years,” leaving the exact age threshold unclear in the registry record.
The primary outcome is described as a number of participants with adverse events, but detailed event definitions, coding procedures, attribution rules, and handling of repeated events are not reported. The record also does not describe the completeness of follow-up or how withdrawals and missing event information were handled. Although the primary timeframe is during open-label therapy over 18 months, the record does not establish that all participants contributed the same observation period.
No analysis results, confidence intervals, or hypothesis tests are reported in the registry entries. The secondary body-weight outcome is named, but its numerical result is not reported in the registry record. The deaths field is blank rather than a reported count. Finally, a sample-size justification, interim-analysis plan, and detailed statistical analysis plan are not reported in the registry record. These gaps limit assessment of precision, outcome ascertainment, and analytic choices.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Follow up Trial for Keppra (Levetiracetam) as Monotherapy in Patients With Newly Diagnosed Epilepsy Coming From N01175 (NCT00175903). — NCT00291655.
- Registry record last updated 2015-05-18; status last verified 2015-04.
- Results first posted 2009-11-13.
- 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
NCT00291655 is a completed phase 3, multicenter, open-label follow-up study of levetiracetam in participants with epilepsy who came from N01175. The registry classifies the design as non-randomized and single-group, with no masking. Enrollment was 130; the recorded start was 2006-06 and primary completion was 2008-04.
The primary outcome assessed safety through adverse-event reporting during an 18-month open-label therapy phase. The safety population included participants treated at least once. The secondary outcome concerned change from baseline in body weight to withdrawal or end of study after 18 months.
The posted safety figures include 6 participants affected by serious adverse events among 130 at risk, and 10 affected by other adverse events among 130 at risk. Six serious-event terms are each listed as 0.8%. The registry reports 0 analyses. It does not provide a randomized comparison, and the counts are descriptive rather than estimates of comparative treatment effect.