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 Test the Pharmacokinetics, Efficacy, and Safety of Brivaracetam in Newborns With Repeated Electroencephalographic Seizures (NCT03325439), a na phase 3 study. The primary outcome is Plasma Concentration of Brivaracetam (BRV) Following First Dose on Day 1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03325439 |
| Phase | Phase 3 |
| Condition | Electroencephalographic Neonatal Seizures |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 9 |
| Arms in the primary outcome | n/a |
| Lead sponsor | UCB Biopharma SRL |
| Results posted | Yes |
2. Clinical Question
Population
Neonates with repeated electroencephalographic seizures that were not adequately controlled with previous antiepileptic drug treatment.
Intervention
Brivaracetam, given intravenously or orally. The record describes exploratory and confirmatory cohorts, but does not report how participants were distributed between them.
Comparator
There was no comparator group. The study is listed as single-group, with allocation not applicable and no masking.
Primary question
What plasma concentrations of brivaracetam were measured after the first dose on Day 1, at the specified post-infusion sampling windows?
The study’s stated purpose included evaluating brivaracetam pharmacokinetics in neonates and identifying an optimal dose in the exploratory cohort for use in confirmatory cohorts. Its primary outcome was pharmacokinetic rather than a direct comparison of seizure outcomes between treatment groups. The registry also lists secondary outcomes concerning seizure burden, response, seizure freedom, and time to reduction in seizure burden.
Because the study had no control group, its treatment observations cannot be contrasted with outcomes under another treatment or under no study treatment. The registry record does not report a randomized allocation or masking. The clinical question is therefore descriptive and exploratory: it concerns measured drug concentrations and listed seizure outcomes among participants treated in this single-group study, not an estimate of comparative treatment effect.
3. Trial Design
The registry lists this as a Phase 3, multicenter, open-label, single-arm study of brivaracetam in neonates with repeated electroencephalographic seizures. The listed enrollment is 9. The study is marked terminated. Its recorded start date is 2019-05-07, and its primary completion date is 2020-09-03; the registry record does not give a reason for termination.
The intervention record includes intravenous and oral brivaracetam. The arm description names an exploratory cohort and confirmatory cohorts, but the record does not give cohort-specific enrollment, treatment allocation, dose details, or results. The stated purpose was to evaluate pharmacokinetics and identify an optimal dose in the exploratory cohort for treatment of participants in confirmatory cohorts. The available record does not establish which cohorts contributed to the reported enrollment.
There is no like-for-like control comparison: the study is listed as single-group, allocation is not applicable, and masking is absent. These design features are important when interpreting seizure outcomes and safety events. Changes observed during treatment cannot be separated from changes that might have occurred over time or under other care using this design alone.
The registry identifies plasma brivaracetam concentration after the first dose on Day 1 as the primary outcome. Pharmacokinetic blood samples were scheduled 0.5 to 1 hour, 2 to 4 hours, and 8 to 12 hours after the infusion. The listed secondary outcomes cover response and seizure-burden measures over the early treatment period and the 96-hour evaluation period. Numerical results for these outcomes are 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: No eligible study participants were enrolled in the Confirmatory Cohorts. The study stopped prematurely due to enrolment challenges, the termination was not linked to any safety issues. The Participant Flow refers to the All Subjects Screened.
Overall Study
| Stage | Exploratory Cohort |
|---|---|
| STARTED | 9 |
| Treated | 6 |
| COMPLETED | 6 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Exploratory Cohort |
|---|---|
| Ineligibility | 3 |
Analysis population for the primary outcome, as defined in the registry: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all study participants who provided at least 1 measurable post-Baseline plasma sample (with recorded sampling time) on at least 1 post-Baseline Visit with documented study drug intake times. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. Here, 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Baseline Characteristics refer to the All Study Participants Screened Set which consisted of all study participants who had signed the Informed Consent form (ICF) and underwent the study inclusion and exclusion criteria of the current protocol. No eligible study participants were enrolled in the Confirmatory Cohorts. The study stopped prematurely due to enrolment challenges, the termination was not linked to any safety issues.
| Characteristic | Unit | Exploratory Cohort |
|---|---|---|
| Participants analysed | 9 | |
| Age, Continuous | weeks | 39.2 (SD 1.9) |
| Age, Customized: Gestational Age <37 weeks | Participants | 2 |
| Age, Customized: Gestational Age >=37 weeks | Participants | 7 |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 3 |
| Race/Ethnicity, Customized: White | Participants | 8 |
| Race/Ethnicity, Customized: Other/mixed | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Plasma Concentration of Brivaracetam (BRV) Following First Dose on Day 1, measured over Pharmacokinetic blood samples were taken 0.5 to 1 hour, 2 to 4 hours, and 8 to 12 hours after the BRV infusion on Day 1.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | nanograms per milliliter (ng/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is plasma concentration of brivaracetam, measured in nanograms per milliliter (ng/mL) after the first dose on Day 1. Samples were taken 0.5 to 1 hour, 2 to 4 hours, and 8 to 12 hours after the brivaracetam infusion. The outcome is summarized using a geometric mean and geometric coefficient of variation. The registry record describes these measurements but does not report numerical concentration results.
Pharmacokinetic measurements help characterize how drug concentrations vary over time after dosing. A geometric mean is a way to summarize measurements that vary multiplicatively; it is often useful for concentration data when values are not symmetrically distributed on the original scale. The geometric coefficient of variation describes relative dispersion around that summary. These statistics describe observed concentrations; by themselves, they do not establish a clinical effect or show that one dose is better than another.
The stated population for this outcome is the Pharmacokinetic Per-Protocol Set. Membership requires at least one measurable post-baseline plasma sample with a recorded sampling time, on at least one post-baseline visit with documented study-drug intake times. The registry record does not provide the numerical estimates, the number of participants contributing at each sampling window, or further detail about how missing samples affected the reported endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The available registry information identifies the study question and design but does not provide numerical results for the primary pharmacokinetic outcome. Although the endpoint specifies geometric mean concentration and geometric coefficient of variation at post-infusion sampling windows, no concentration estimates or interval estimates are reported in the registry record. As a result, the posted information does not show the measured concentration pattern or its precision.
The record lists 15 outcome measures and 0 analysis entries. It names secondary outcomes for early response, reductions in nonsevere and severe seizure burden, changes in average seizure burden through the 96-hour evaluation period, seizure freedom, and time to reduction in seizure burden. Those outcome definitions do not substitute for results: the registry record does not report numerical values for these measures. It is therefore not possible to describe the observed seizure outcomes from the information recorded.
Design limits the conclusions that could be drawn even if outcome values were available. The study is single-arm and open-label, with no randomized comparator. A change from baseline in a treated group would describe what happened during the observed period, but would not by itself estimate what would have happened under an alternative treatment or without brivaracetam. The absence of a control group also limits interpretation of adverse events, because events occurring during the study cannot be attributed to treatment by comparison with an untreated or differently treated group.
The registry lists enrollment of 9 and marks the study terminated. It does not report why the study was terminated, whether the planned cohorts were completed, or whether termination altered the intended analysis. The enrollment figure should not be treated as the number contributing to every endpoint: the pharmacokinetic population has its own sample eligibility requirements, and endpoint-specific denominators are not reported.
Safety entries record serious adverse events affecting 1 participant among 9 at risk, other adverse events affecting 5 among 9 at risk, and 0 deaths. Apnoea is listed as the top serious-event term at 11.1%. These figures are descriptive entries in the registry; they do not establish that brivaracetam caused an event, and they do not provide comparative safety estimates.
In short, the record supports a description of the study’s design, planned outcome measurements, and recorded safety counts. It does not support a quantitative interpretation of the primary pharmacokinetic endpoint or the listed seizure outcomes because their numerical results are not reported in the registry record.
9. Statistical Methods Explained
What does the primary summary measure?
The primary outcome uses a geometric mean to summarize plasma brivaracetam concentrations. In general, an arithmetic mean summarizes values by their additive center, whereas a geometric mean is based on multiplicative relationships and is commonly used for positive measurements that vary proportionally. This can make the summary more suitable when values are skewed on the original measurement scale. It does not remove the need to examine variability, sample counts, or the distribution of the measurements.
The geometric coefficient of variation describes relative spread around the geometric mean. In general, variability matters because a similar average can arise from measurements that are tightly clustered or widely dispersed. The registry identifies this dispersion measure but provides no numerical estimate for it. Without the concentration summaries and their uncertainty, the magnitude and precision of the pharmacokinetic findings cannot be assessed.
Why collect samples at different times?
Concentrations were scheduled at 0.5 to 1 hour, 2 to 4 hours, and 8 to 12 hours after the infusion on Day 1. In general, measurements at different times can describe how concentrations change after dosing. The registry lists these sampling windows but does not report the measured values at any window. Nor does it report whether every participant contributed a sample at each time window. The listed schedule should not be mistaken for evidence that all scheduled samples were collected.
What does the pharmacokinetic analysis population mean?
The named Pharmacokinetic Per-Protocol Set includes participants who provided at least one measurable post-baseline plasma sample with a recorded sampling time on a post-baseline visit with documented study-drug intake times. This definition makes usable sample and dosing-time information relevant to inclusion in the endpoint population. In general, per-protocol sets can differ from the enrolled group when participants lack the required measurements or documentation. The registry does not report the size of this population or how many observations contributed to each sampling window.
Missing measurements can affect interpretation if the participants with usable samples differ from those without them. The record does not report the extent or reasons for missing pharmacokinetic samples, or a missing-data method. It is therefore not possible to evaluate whether the reported endpoint, if available elsewhere, would represent all enrolled participants or only those with qualifying samples.
What can a single-group design estimate?
In general, a single-group study can describe measurements among participants who receive the study intervention. It lacks a concurrent control group to separate intervention-associated changes from other influences, such as changes over time or other care. This matters for seizure outcomes based on change from baseline: a before-and-after difference would not, on its own, establish that the intervention produced the change. In this record, the study is explicitly single-group, and numerical seizure outcome results are not reported.
The study is also open-label and has no masking. In general, lack of masking can affect expectations, care decisions, event reporting, or outcome assessment, depending on how outcomes are collected. Continuous video-electroencephalography is listed among the secondary outcome measures, but the registry record does not describe assessor masking or provide analysis details. No conclusion about the extent of any bias can be drawn from the design label alone.
How should significance testing and planning be understood?
The registry lists 0 analysis entries. It does not report statistical tests, confidence intervals, an analysis plan, or a sample-size justification. A confidence interval, in general, expresses the uncertainty around an estimated quantity under a stated statistical model; it is not a guarantee that the true value lies within the interval. Since no primary-outcome estimate or interval is recorded, precision cannot be evaluated from the registry record.
The registry’s planning assumptions describe illustrations based on an observed effect, two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. Those are planning assumptions, not evidence that the clinical study used a two-arm design: the recorded trial is single-arm. Sample-size illustrations are not observed power, and the record does not give a trial-specific sample-size justification or indicate that those assumptions were the design basis. The effect values and resulting sample-size estimates are not included in the record details, so no numerical planning estimate can be interpreted.
More generally, a planned sample size is tied to the effect size and variability assumed, the target power, the significance level, and the analysis method. If those assumptions do not match the eventual study or the clinical question, the calculation may not describe the precision achieved. The registry does not provide enough statistical-plan detail to assess such alignment for this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 15 outcome measures, including the primary pharmacokinetic outcome and secondary seizure-related outcomes. When a study examines several outcomes or several comparisons, the chance of at least one apparently unusual result can increase if each is assessed separately. Statistical approaches can address multiplicity, but the appropriate approach depends on the planned questions and analysis strategy. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a complete statistical analysis plan.
The absence of a reported multiplicity strategy should not be read as proof that none was used outside the registry. It means that the registry record does not provide enough information to assess how multiple outcomes were handled. The record lists 0 analysis entries and does not report numerical results for the primary or secondary outcomes, so neither statistical significance nor the consistency of findings across outcomes can be evaluated.
The pharmacokinetic analysis population has a stated eligibility definition: participants needed at least one measurable post-baseline plasma sample with recorded sampling time and documented study-drug intake times. The record does not state the number meeting that definition, the amount of missing data, the reasons for missing samples, or whether a separate method addressed missingness. It also does not describe analysis populations for the seizure outcomes. These omissions matter because endpoint-specific data availability may differ from enrollment, and the enrolled group should not be assumed to be the analysis denominator for every measure.
The registry does not report whether sensitivity analyses examined the effect of missing data, whether interim analyses were conducted, or whether the analysis plan changed. These items are not reported in the registry record; their absence from the record is not evidence that a particular procedure was or was not conducted.
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 |
|---|---|---|---|
| Exploratory Cohort | 1 | 9 | 11.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Exploratory Cohort | 0 of 9 |
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 |
|---|---|
| Exploratory Cohort | 5 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Exploratory Cohort |
|---|---|---|
| Apnoea | Respiratory, thoracic and mediastinal disorders | 1 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Exploratory Cohort |
|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 1 of 9 |
| Dry eye | Eye disorders | 1 of 9 |
| Ammonia increased | Investigations | 1 of 9 |
| Liver function test abnormal | Investigations | 1 of 9 |
| Oxygen saturation decreased | Investigations | 1 of 9 |
| Hyperglycaemia | Metabolism and nutrition disorders | 1 of 9 |
| Hypokalaemia | Metabolism and nutrition disorders | 1 of 9 |
Serious events with the highest arm-level rate: apnoea (11.1%).
The registry safety record lists the exploratory cohort with 9 participants at risk for serious adverse events and 1 affected, and 9 at risk for other adverse events and 5 affected. It records 0 deaths. Apnoea is the top listed serious adverse-event term, at 11.1%. These are descriptive counts and a reported percentage, not estimates from a controlled comparison.
The at-risk and affected figures describe participants with recorded events in the registry’s categories. They do not indicate whether an event was judged related to brivaracetam, whether participants experienced more than one event, or when events occurred. The registry record does not provide those details. The serious-event term and percentage should therefore be read as a safety listing, not as evidence of causation or a comparative risk.
Because the study has no control group, the safety entries cannot show whether event frequency differed from that under another treatment or usual care. The small listed cohort also means the registry counts alone cannot characterize less common risks with precision. The record does not report further safety analysis or uncertainty estimates.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a Phase 3, open-label, single-arm study of brivaracetam in neonates with repeated electroencephalographic seizures, with pharmacokinetic concentration as the primary outcome. It also records the sampling windows, the planned seizure-related secondary outcomes, enrollment of 9, termination status, and selected adverse-event counts. These details describe the study and the measurements it was intended to make.
The record does not report numerical results for the primary concentration endpoint or the listed seizure outcomes. It therefore cannot show the concentrations observed, how variable they were, or what seizure changes were recorded. Without those outcome estimates and their uncertainty, the size and precision of any observed effect cannot be assessed. The record also gives no reason for termination, no detailed treatment exposure information, and no endpoint-specific analysis denominators.
Even with outcome estimates, the single-arm design would not establish a comparative treatment effect. A treated-group observation does not reveal what would have occurred for comparable participants under a different treatment. Open-label conduct and the lack of masking are additional design features to consider, although the registry does not provide enough detail to quantify their influence.
The safety counts document events in the registry record, but do not establish that brivaracetam caused them. No control group or comparative safety estimate is reported. The appropriate reading is descriptive: the record identifies events and counts, while leaving attribution and comparative risk unresolved.
Accordingly, the information recorded supports understanding the study’s design and the scope of its planned measurements, but it does not support a numerical judgment about pharmacokinetic findings, seizure outcomes, or comparative safety. Those conclusions would require results and analysis details not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable because its primary question concerns pharmacokinetics in neonates, while its listed secondary outcomes include seizure measures. Pharmacokinetic concentration summaries and seizure outcomes answer different questions. Concentration measurements describe drug exposure at specified times; seizure outcomes describe clinical or electroencephalographic events over defined periods. A concentration result alone would not establish a seizure outcome, and a seizure outcome alone would not characterize the concentration pattern.
The single-arm design also makes the distinction between description and comparison especially important. The study can be understood as an investigation of measurements among treated participants, but it does not include a randomized control group for estimating a contrast between treatment strategies. This limitation applies to both efficacy-related outcomes and safety interpretation.
Enrollment is listed as 9, and the study is marked terminated. The pharmacokinetic endpoint has its own analysis-population criteria, so enrollment cannot be assumed to equal the number contributing to that endpoint. The registry does not report endpoint-specific denominators or numerical results. This highlights why transparent reporting of populations, missing measurements, estimates, and uncertainty is central to statistical interpretation.
The record also lists 15 outcome measures but no analysis entries. Without reported results, analysis methods, or a multiplicity approach, readers cannot determine how outcomes were estimated or how uncertainty across multiple questions was handled. The main statistical lesson is therefore not a treatment conclusion, but the need to distinguish a clearly stated measurement plan from evidence about observed outcomes.
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 registry record marks the study terminated but does not explain why. It does not report whether the termination affected recruitment, cohort completion, follow-up, or the planned analyses. The listed enrollment is 9, but the record does not give cohort-specific enrollment or endpoint-specific denominators. The exploratory and confirmatory cohort labels therefore do not establish which cohorts contributed to the recorded study population or outcome data.
The primary endpoint is defined with sampling windows and a named pharmacokinetic analysis population, but numerical concentration results, variability estimates, and uncertainty intervals are not reported. The registry also does not give the number of usable samples at each time window or the extent and handling of missing samples. These gaps prevent assessment of both the endpoint’s precision and the representativeness of the analysis population.
The registry lists seizure-related secondary outcomes but gives no numerical results for them. It does not report the statistical analysis plan, handling of multiple outcomes, interim analyses, or a trial-specific sample-size justification. The planning assumptions recorded for sample-size illustrations describe a two-arm calculation, whereas the actual design is listed as single-group; those planning assumptions should not be treated as the study design or as observed power.
Finally, the lack of a control group and masking limits causal and comparative interpretation. Safety events are listed descriptively, with no reported attribution or comparative analysis. These limitations concern what can be concluded from the registry record; they do not establish that unreported procedures or results do not exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Test the Pharmacokinetics, Efficacy, and Safety of Brivaracetam in Newborns With Repeated Electroencephalographic Seizures — NCT03325439.
- Registry record last updated 2024-04-08; status last verified 2024-04.
- Results first posted 2024-01-16.
- 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
NCT03325439 is listed as a Phase 3, multicenter, open-label, single-arm study of intravenous or oral brivaracetam in neonates with repeated electroencephalographic seizures. Enrollment is recorded as 9, and status is terminated. The recorded start date is 2019-05-07 and the primary completion date is 2020-09-03.
The primary outcome is plasma brivaracetam concentration after the first dose on Day 1, summarized by geometric mean and geometric coefficient of variation at specified post-infusion sampling windows. The record lists 15 outcome measures and 0 analysis entries, but numerical primary and secondary outcome results are not reported in the registry record.
Safety entries list 1 participant affected by a serious adverse event among 9 at risk, 5 affected by other adverse events among 9 at risk, and 0 deaths. Apnoea is listed as the top serious-event term at 11.1%. The study has no control group, so these safety figures are descriptive rather than comparative.