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 Dosing of Levetiracetam (Keppra) in Neonates (NCT01239212), a non-randomized phase 1, phase 2 study. The primary outcome is Pharmacokinetic Profile.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01239212 |
| Phase | Phase 1, Phase 2 |
| Condition | Seizures |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 7 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Children's Hospital Medical Center, Cincinnati |
| Results posted | Yes |
2. Clinical Question
Population
Neonates with seizures, described in the study objectives as term and late preterm infants. The official title refers to full term and preterm neonates. The registry record reports an enrollment of 7 and states that all participants had adequate levels drawn for analysis.
Intervention
A 50 mg/kg intravenous levetiracetam loading dose. The study also sought steady-state drug-level data in neonates who remained on maintenance doses.
Comparator
There was no comparator group. This was a non-randomized, single-group study, so the record does not provide a like-for-like control comparison.
Primary question
What pharmacokinetic profile, particularly clearance, was observed after the loading dose? Drug levels were planned at several post-dose times, with a later steady-state level if an infant remained on maintenance treatment.
The primary objective was to determine the pharmacokinetic profile of the loading dose in term and late preterm infants with seizures. Pharmacokinetics describes how drug concentrations change over time and how the body handles a drug. The stated primary outcome was clearance, expressed in ml/min/kg. The registry describes the reported measure as the median maximum clearance rate measured in each participant from levetiracetam levels at the specified time points.
The study also had secondary objectives: evaluating safety and efficacy and obtaining steady-state level data. Those objectives are not equivalent to a controlled test of clinical benefit. With one group and no comparator, the central question is descriptive: what drug-level information was obtained in the enrolled neonates, and what safety events were recorded during the study? The registry record does not report a numerical clearance estimate or a numerical efficacy result.
3. Trial Design
This was a completed Phase 1 and Phase 2 study, with a single-group model, non-randomized allocation, and no masking. The registry lists enrollment as 7. The sponsor was Children's Hospital Medical Center, Cincinnati. The study start is recorded as 2010-09 and primary completion as 2011-07.
All participants received the named intervention, levetiracetam. The intended dose was a 50 mg/kg intravenous loading dose. No untreated, placebo, or active-comparator group is described. Consequently, the design is suited to describing drug levels and observed events in the enrolled group, but not to estimating a comparative treatment effect against a control group.
Blood levels for levetiracetam and its metabolite L057 were planned at 5-20 minutes, 1-2 hours, and 6-10 hours after the dose. For infants who remained on maintenance doses, a steady-state level was to be drawn 4-7 days after the loading dose. The registry says that all participants had adequate levels drawn for analysis, but it does not state whether each participant contributed every scheduled sample or whether any participant contributed the conditional steady-state sample.
The record describes the study as completed. It does not report a randomized allocation procedure, a masking procedure, or a control arm. Sample-size justification, planned interim analyses, and a fuller statistical analysis plan are not reported in the registry record. These omissions matter when judging the precision and scope of conclusions: a small, uncontrolled pharmacokinetic study can describe measurements in its enrolled group, while it cannot provide the same comparative evidence as a randomized controlled trial.
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 | Single Arm, 50 mg/kg of Levetiracetam |
|---|---|
| STARTED | 7 |
| COMPLETED | 7 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: all participants had adequate levels drawn for analysis
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 | Single Arm, 50 mg/kg of Levetiracetam |
|---|---|---|
| Participants analysed | 7 | |
| Age, Categorical: <=18 years | Participants | 7 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 4 |
| Region of Enrollment: United States | participants | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Pharmacokinetic Profile, measured over 5-20 minutes after the dose, 1-2 hours after the dose, 6-10 hours after the dose, and possibly 4-7 days after loading dose (if infants remained on maintenance doses).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | ml/min/kg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled Pharmacokinetic Profile, with clearance reported in ml/min/kg. The registry describes the parameter as a median and the dispersion as the full range. The stated outcome is the median maximum clearance rate measured in each participant by evaluating levetiracetam concentrations at the post-dose time points using MW Pharm.
Clearance is a pharmacokinetic measure of how efficiently drug is removed from the body relative to its concentration. In general, concentration measurements taken at multiple times help characterize changes in drug levels and support estimation of the drug's disposition. Reporting clearance per kilogram expresses the measure in relation to body weight, which is relevant when dosing is specified per kilogram.
The multiple planned sampling times make the endpoint a profile over time rather than a single concentration reading. The later sample was conditional: it was planned for infants who remained on maintenance doses. The registry record does not report the numerical median clearance, the full range, or separate numeric results at the individual sampling times. It therefore describes what the endpoint was intended to measure, but does not provide the estimate needed to assess its observed magnitude or precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study addresses an important descriptive question: what levetiracetam clearance profile was observed after a 50 mg/kg intravenous loading dose in the enrolled neonates with seizures? The posted record identifies the endpoint, units, planned sampling times, and summary format. It does not include a numerical clearance result. Without that estimate or its full range, the magnitude and variability of clearance cannot be assessed from the registry record.
The design was a non-randomized single group, with no masking and no comparator. This means the observations are not a treatment-versus-control contrast. Any measured drug levels or recorded events describe the participants receiving levetiracetam in this study; the design does not isolate how those observations would differ under another treatment or no treatment. No efficacy estimate is reported in the registry record, so the secondary objective to evaluate efficacy cannot be interpreted as a posted efficacy finding.
The primary outcome was summarized using a median and full range. In general, a median describes the middle of ordered observations and is less affected than a mean by unusually high or low values. A full range gives the lowest and highest observations, but it does not show how values are distributed between those endpoints. Here, because neither the median nor range is numerically reported, even a descriptive account of the observed clearance values is unavailable.
The record states that all participants had adequate levels drawn for analysis. That statement supports the availability of levels considered adequate for the stated analysis, but it does not specify the number of samples at each time point or establish that each participant had every planned measurement. The steady-state sample was conditional on continued maintenance dosing, and the record does not say how many participants met that condition or report a steady-state result.
Safety reporting lists 0 participants with serious adverse events among 7 at risk and 0 with other adverse events among 7 at risk. These are registry counts for the listed categories; the death count is not reported. Such counts are descriptive, not a comparison with another group. With the numerical pharmacokinetic result absent and no control group, the record supports a description of the study's purpose, design, sampling approach, and posted safety counts, but not a quantified estimate of clearance or a comparative conclusion.
The registry lists one outcome measure and zero analyses. A stated endpoint is not itself a result. In general, interpretation of an estimate also depends on its precision, commonly expressed with an interval around the estimate. No confidence interval is reported in the registry record for clearance. Thus, there is no posted estimate or interval from which to judge how precisely the endpoint was measured.
9. Statistical Methods Explained
The statistical information in the registry is limited. It names a primary pharmacokinetic outcome, gives its units and summary format, and describes the sampling schedule. It does not report an analysis result or a fuller statistical analysis plan. The explanations below distinguish the endpoint's stated features from general statistical principles.
What does the endpoint summarize?
The outcome is clearance in ml/min/kg. The registry specifies a median and full range, and says that the median maximum clearance rate was measured in each participant by evaluating levels at the time points using MW Pharm. This wording describes a participant-level measure and a group summary, but it does not provide the underlying values, the numerical summary, or details of the software procedures used. No additional calculation steps should be inferred from the description.
In general, a median is the middle value after observations are ordered. It can be useful when data are skewed or when extreme observations might pull a mean away from the typical observation. A full range reports the endpoints of the observed values. It conveys how far apart the most extreme observations are, but it does not reveal whether most values cluster closely together or are spread across that interval. Because the registry contains no numerical median or range, these summaries cannot be used to characterize the observed clearance distribution.
Why collect levels at several times?
The planned samples were at 5-20 minutes, 1-2 hours, and 6-10 hours after the dose. The record also describes a steady-state sample at 4-7 days after the loading dose if an infant remained on maintenance doses. In general, repeated concentration measurements can describe how drug levels change over time. A pharmacokinetic profile can use those changes to characterize drug disposition, rather than relying on one concentration at one time.
The record says the levels included levetiracetam and metabolite L057. It describes clearance as evaluated from levetiracetam levels. It does not report a separate metabolite result. Nor does it provide concentration values, estimates for each time point, or a numerical clearance result. The later steady-state sample was conditional, so it should not be treated as a measurement collected for every participant.
What does the design allow?
In general, a single-group study can describe measurements and events in the people enrolled, but without a comparator it cannot estimate a between-group difference. Non-randomized allocation and no masking are consistent with the record's stated design; no randomized or blinded comparison is described. The lack of a control group is especially important for interpretation of safety and efficacy objectives: observed events or clinical changes cannot be contrasted with a control group's experience using this design.
The registry reports enrollment as 7 and identifies a single arm receiving the 50 mg/kg dose. The record does not report a sample-size justification. It is therefore not possible to determine from the registry why that enrollment was selected or what precision was anticipated. No interim analysis plan or fuller statistical analysis plan is reported in the registry record.
How should precision be assessed?
In general, a point estimate gives a central numerical summary, while a confidence interval describes uncertainty around an estimate under a specified statistical procedure. A narrow interval generally indicates greater precision than a wide interval, although precision does not by itself establish clinical importance. No confidence interval is reported for the clearance endpoint. Since the endpoint's numerical median and full range are also absent, neither its observed scale nor its precision can be assessed from the registry record.
With small datasets, individual observations can have substantial influence on a summary, and full ranges can be particularly sensitive to extreme observations. General statistical practice therefore considers the raw distribution and uncertainty measures alongside a central summary. The registry record does not report participant-level clearance values or a distributional plot in its outcome description, so those features cannot be evaluated from the outcome information recorded.
What is not established by the record?
The registry lists one outcome measure and zero analyses. That distinction is important: an outcome definition describes what investigators intended to measure, whereas a reported analysis supplies a result. Here, the outcome description is detailed about units, summary form, timing, and the approach to evaluating levels, but it does not provide numeric findings.
There is no reported hypothesis test, p-value, confidence interval, adjusted estimate, or comparison in the registry record. This does not establish that none were considered in other study materials; it means they are not reported in the registry record. The same caution applies to data handling, modeling choices, and any plan for multiple outcomes. These elements should not be reconstructed from the endpoint description alone.
General statistical interpretation also distinguishes variability among participants from uncertainty in a group estimate. A full range describes observed variability, whereas a confidence interval addresses uncertainty in an estimated quantity under assumptions. They answer different questions. Neither numerical summary is present for clearance in the registry record, so the reported design and endpoint can be explained, but the observed pharmacokinetic result cannot be quantified.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure: the pharmacokinetic profile, with clearance as the reported outcome. It also describes secondary objectives to evaluate safety and efficacy and obtain steady-state drug-level data. The record lists zero analyses and does not report a numerical clearance result or numeric results for the secondary objectives.
When a study evaluates multiple outcomes or makes multiple statistical comparisons, the chance of a false-positive finding can increase if each is tested separately. General methods for addressing multiplicity include defining a primary outcome in advance, adjusting inference, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, a set of hypothesis tests, or an analysis plan; no approach should be assumed.
For missing data, the record states that all participants had adequate levels drawn for analysis. It does not specify sample availability at each planned time point or describe missing-data handling. The steady-state measurement was conditional on remaining on maintenance doses, and the record does not report how many participants had that measurement. No imputation or other missing-data procedure is reported in the registry record.
The record does not define analysis populations beyond stating that all participants had adequate levels for analysis. It does not report whether an intention-to-treat, per-protocol, or other analysis population was used. These labels should not be inferred from the description of adequate levels. The endpoint information supports understanding the intended measurement, but not reconstruction of the analysis population or multiplicity procedures.
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 |
|---|---|---|---|
| Single Arm, 50 mg/kg of Levetiracetam | 0 | 7 | 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 |
|---|---|
| Single Arm, 50 mg/kg of Levetiracetam | 0 of 7 |
The registry lists one group, titled Single Arm, 50 mg/kg of Levetiracetam. It records 7 at risk for serious adverse events and 0 affected. It also records 7 at risk for other adverse events and 0 affected. The death count is not reported in the registry record, and no top serious adverse-event terms are listed.
These figures are descriptive counts in the study group. They are not a comparison with an untreated or alternative-treatment group, because the design had no comparator. The registry record does not provide event-level details, observation duration for safety, or definitions for the listed adverse-event categories. The zero affected counts therefore should be read only as the posted counts for those categories, not as evidence that no events of any kind occurred or that risk was absent.
In general, safety counts depend on what was monitored, how events were defined, and how long participants were observed. A small study can also provide limited information about uncommon events. The record's safety counts should be interpreted within those descriptive limits, without converting them into a comparative rate or a broader claim.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed Phase 1 and Phase 2 single-group study examined intravenous levetiracetam in neonates with seizures. The intervention was a 50 mg/kg loading dose. The primary objective concerned pharmacokinetics, with clearance as the stated outcome and drug levels planned at multiple times after dosing. The study also had secondary objectives concerning safety, efficacy, and steady-state levels.
What the posted record does not establish is a numerical clearance result. Although the outcome description specifies a median and full range, it does not give their values. It also does not report a numerical efficacy finding, concentration estimates, or a steady-state result. The outcome definition and sampling plan cannot substitute for observed results.
The safety record gives 0 affected for serious adverse events and 0 affected for other adverse events, with 7 at risk in each category. These counts are not a comparison with another group and do not establish absence of all possible adverse events. The death count is not reported in the registry record.
More broadly, the single-group design can describe what was measured in the enrolled participants, but cannot show how outcomes would compare under another treatment. The registry record does not report inferential analyses, confidence intervals, or a statistical plan. Consequently, it does not permit an assessment of the precision of clearance estimates or comparative effects. The study's objectives and methods are clear enough to understand the kind of evidence sought, but the posted results are insufficient to quantify the primary pharmacokinetic finding.
13. Why This Trial Matters Statistically
This study is statistically notable for the difference between a well-described measurement plan and the absence of a posted numerical outcome. The registry identifies clearance as the primary endpoint, states its units and summary form, and describes repeated post-dose levels. Yet it does not report a clearance estimate or range. For readers, this illustrates why outcome definitions and results must be distinguished: a specified endpoint explains what was intended to be measured, not what value was observed.
The study also illustrates the role and limits of an early-phase, single-group design. Repeated drug-level measurements can provide descriptive pharmacokinetic information, while a comparator is needed for a direct treatment-group contrast. The absence of randomization and masking, and the lack of a control arm, define the scope of what the design can address. Its stated questions about safety and efficacy should not be read as controlled tests of either.
The registry's safety counts are another useful example of descriptive reporting. Counts of 0 affected in the listed categories are informative as posted counts, but they do not quantify a comparative difference and do not establish that all possible events were absent. Denominators, observation details, event definitions, and the absence of a control group shape interpretation.
Finally, the record makes visible reporting gaps that affect statistical interpretation: it lists zero analyses, does not report a confidence interval or numerical clearance summary, and does not describe a fuller statistical plan. Those omissions prevent assessment of the magnitude and precision of the main pharmacokinetic endpoint. A reader can understand the intended measurement and design, but should not mistake that methodological description for a reported result.
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 primary limitation for interpreting the pharmacokinetic objective is that the registry record does not report the numerical clearance result, despite specifying the endpoint and summary method. Without the median or full range, the observed level of clearance and the variation among participants cannot be assessed. No confidence interval is reported to characterize uncertainty in an estimate.
The study had a single group and no comparator. Its non-randomized design and absence of masking further mean that the record does not describe a blinded comparative assessment. It can provide descriptive information about the enrolled group, but cannot provide a treatment-versus-control estimate. The secondary efficacy objective is not accompanied by a numerical efficacy result in the registry record.
The registry says all participants had adequate levels drawn for analysis, but does not report the number of measurements available at each scheduled time. The steady-state level was conditional on remaining on maintenance doses, and no number of participants with such a measurement or numerical steady-state result is reported. This limits assessment of completeness across the planned profile.
The record does not report a sample-size justification, interim analyses, detailed statistical analysis plan, missing-data procedure, analysis population definitions, or multiplicity strategy. It lists zero analyses. These details should be treated as unreported rather than inferred. Safety interpretation is also limited by the lack of event details and a comparator; the death count is not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dosing of Levetiracetam (Keppra) in Neonates — NCT01239212.
- Registry record last updated 2021-09-05; status last verified 2021-08.
- Results first posted 2014-09-08.
- 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.
18. Record Summary
NCT01239212 is a completed Phase 1 and Phase 2, non-randomized, single-group study titled Dosing of Levetiracetam (Keppra) in Neonates. Enrollment was 7, with no masking and no comparator group. The intervention was a 50 mg/kg intravenous levetiracetam loading dose in neonates with seizures.
The primary outcome was clearance in ml/min/kg, summarized as a median and full range, based on levetiracetam levels planned at several post-dose times. A steady-state level was planned for infants remaining on maintenance doses. The registry record does not report the numerical clearance result. Safety counts list 0 affected for serious adverse events and 0 affected for other adverse events, with 7 at risk in each category; deaths are not reported. The record lists one outcome measure and zero analyses.