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 Single-dose and Steady-state Pharmacokinetics of BIA 2-093 and Its Metabolites (NCT02172755), a non-randomized phase 1 study. The primary outcome is Maximum Drug Concentration (Cmax).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02172755 |
| Phase | Phase 1 |
| Condition | Epilepsy |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bial - Portela C S.A. |
| Results posted | Yes |
2. Clinical Question
Population
Healthy elderly subjects aged 65 years or more and healthy young subjects aged between 18 and 40 years.
Intervention
BIA 2-093, given as a single 600 mg dose and then as 600 mg once daily for 8 days.
Comparator
The non-randomized comparison is between the elderly and young subject groups. It is not a randomized, like-for-like control comparison.
Primary question
How does age relate to the pharmacokinetic profile of BIA 2-093 and its active metabolites, including maximum observed drug concentration?
The study’s stated purpose was to determine the effects of age on the pharmacokinetic profile of BIA 2-093 and its active metabolites. The primary outcome is maximum drug concentration, or Cmax. The registry also lists Tmax, the time of maximum observed concentration, and AUC0-t, the area under the plasma concentration-time curve to the last measurable time point, as secondary outcomes.
The registry describes healthy subjects, with separate age-based groups, rather than a study population selected for epilepsy. Epilepsy appears as the listed condition, but the record does not explain that listing. The central question is pharmacokinetic: whether the concentration profiles differ by age under the stated dosing schedule. It is not a direct test of seizure control, clinical benefit, or comparative treatment effectiveness.
The registry record does not report numerical Cmax results, age-group estimates, an estimated age-related contrast, or uncertainty around such a contrast. It therefore does not establish the direction or size of any observed age difference in the posted record.
3. Trial Design
This was a Phase 1, completed, non-randomized, unmasked, parallel study. The registry lists an enrollment of 30. The elderly group included 14 subjects aged 65 years or more, and the young group included 16 subjects aged between 18 and 40 years. The study started in 2002-06 and had primary completion in 2002-08.
Both groups were scheduled to receive the same BIA 2-093 regimen. Phase A consisted of a single 600 mg dose. Phase B consisted of 600 mg once daily for 8 days, beginning 96 hours after the Phase A dose. This arrangement allows concentration measurements after a single dose and during the repeated-dose period, according to the registry description.
Because allocation was non-randomized and the arms are defined by age, the groups are not randomized treatment arms. Age is the characteristic of interest, not an assigned study treatment. Differences between the groups could therefore reflect age or other differences between the groups; the registry record does not report adjustment methods or enough participant characteristics to assess that possibility.
The primary endpoint was maximum drug concentration, reported as a mean with standard deviation. Sampling was scheduled after the single dose on Day 1, before daily doses from Day 5 to Day 11, and after the last dose on Day 12. The registry also lists Tmax and AUC0-t as secondary outcomes. It lists 3 outcome measures but reports 0 analyses. Numerical outcome results and the analysis plan are not reported in the registry record.
The study was sponsored by Bial - Portela C S.A. Its completed status describes the study record, not whether the registry contains a full report of all planned measurements or 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 | Elderly Subjects | Young Subjects |
|---|---|---|
| STARTED | 14 | 16 |
| COMPLETED | 12 | 12 |
| NOT COMPLETED | 2 | 4 |
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 | Elderly Subjects | Young Subjects | Total |
|---|---|---|---|---|
| Participants analysed | 14 | 15 | 29 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 15 | 15 |
| Age, Categorical: >=65 years | Participants | 14 | 0 | 14 |
| Sex: Female, Male: Female | Participants | 7 | 8 | 15 |
| Sex: Female, Male: Male | Participants | 7 | 7 | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Drug Concentration (Cmax), measured over Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | ng/mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is maximum drug concentration, abbreviated Cmax, measured in ng/mL. Cmax is the highest observed concentration of a drug in the sampled blood concentration profile over the specified observation period. It is used in pharmacokinetic studies to describe peak exposure after a dose. It is distinct from the timing of the peak, which is captured by Tmax, and from an area-under-the-curve measure, which summarizes concentration across time.
The registry describes repeated sampling after the single Phase A dose: pre-dose and at ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose on Day 1. During the multiple-dose period, trough levels were scheduled before the daily dose from Day 5 to Day 11 inclusive. On Day 12, sampling was scheduled before dosing and at ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose.
Frequent sampling helps describe the concentration profile and identify its observed maximum within the scheduled measurements. The maximum observed value depends on the sampling schedule: a peak occurring between sample times may not be captured exactly. The registry also notes that BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093. It does not report numerical Cmax estimates for the parent drug or metabolites, nor does it explain how their results were analyzed together or separately.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question, dosing schedule, endpoint definition, and age-based group structure. It does not provide numerical results for Cmax or the listed secondary outcomes. In particular, there is no reported mean, standard deviation, age-group contrast, confidence interval, test statistic, or p-value for the primary endpoint. The direction, magnitude, and precision of an age-related difference therefore cannot be determined from the posted record.
The endpoint is recorded as a mean of a continuous measure, with standard deviation as its dispersion measure. These describe different features: the mean indicates the group’s average concentration, while the standard deviation describes variability among measurements or subjects, depending on the analysis unit. Without posted estimates and a clear analysis population, neither feature can be assessed for this study.
The non-randomized design is important to interpretation. The groups differ by age by design, and the registry does not report a randomized allocation process. A difference in observed concentration, if reported elsewhere, would not automatically isolate the effect of age from other group differences. The record does not report an adjusted analysis, covariates, or participant-level characteristics that would clarify whether such factors were considered.
Pharmacokinetic outcomes answer questions about drug concentration over time. They do not, by themselves, establish a clinical effect on epilepsy or another health outcome. The registry’s condition listing does not change the stated healthy-subject population or turn Cmax into a clinical efficacy endpoint.
The record’s enrollment and group descriptions give the planned or recorded study scale, but no outcome-level denominators or missing-measurement information are reported. It is not possible to tell from the registry whether all enrolled subjects contributed to every concentration summary, whether any scheduled samples were unavailable, or whether the stated means would use all scheduled observations.
Planning illustrations based on an observed effect are not observed power. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. The record does not include numerical outcome estimates or the resulting planning values in the registry record for interpretation. Such planning calculations cannot replace reporting the actual estimated effect and its uncertainty.
The appropriate reading is therefore limited: the registry records a completed pharmacokinetic study designed to examine age-related profiles under a defined regimen, but its posted record does not give the numerical primary-endpoint findings needed to judge the observed difference or its precision.
9. Statistical Methods Explained
What does Cmax represent?
Cmax is the maximum concentration observed in the sampled profile. It summarizes the peak measured concentration after dosing, while Tmax identifies when that peak was observed. AUC0-t captures exposure across the interval from dosing to the last measurable time point. These quantities describe different aspects of pharmacokinetics and are not interchangeable. A group may have a different peak, a different time to peak, or a different concentration profile over time; one measure alone does not describe every feature.
Sampling times matter because Cmax is based on observations at scheduled times. A concentration peak between samples may be missed, so the observed maximum is not necessarily the exact biological peak. The registry’s schedule includes measurements after the single dose, trough measurements during repeated dosing, and post-last-dose measurements on Day 12. This design records concentration over time, but the registry does not report the measured profiles or the resulting endpoint summaries.
What do the mean and standard deviation tell the reader?
The primary endpoint is described as a mean of a continuous measure, with standard deviation. In general, a mean gives a central summary, and a standard deviation describes the spread of observations around that mean. The standard deviation is not the same as the standard error, which describes uncertainty in an estimated mean. A confidence interval is another way to communicate uncertainty around an estimate; its width depends on factors including variability and the amount of information available. No confidence interval or standard error for Cmax is reported in the registry record.
Continuous concentration measurements can have different distributions, and the choice of summary and analysis can affect interpretation. A mean and standard deviation are descriptive summaries; they do not by themselves establish whether a group contrast is statistically distinguishable from no difference. The registry does not report a statistical test, model, transformation, or assumptions used for the primary outcome. It is therefore not possible to say which inferential approach, if any, was used.
How does the design affect comparisons?
The study is non-randomized and parallel. The groups were defined by age, and the record does not describe random assignment. In a randomized comparison, assignment can help balance measured and unmeasured characteristics on average; that protection cannot be assumed for this age-based comparison. Any contrast between groups would need to be interpreted with attention to possible differences other than age. The registry does not report baseline characteristics, adjustment variables, matching, or a model for controlling such differences.
The regimen was the same in the two groups: a single 600 mg dose followed by 600 mg once daily for 8 days, with Phase B beginning 96 hours after the Phase A dose. This common schedule makes the intended dosing conditions comparable as described, but it does not establish that all exposures, adherence, or other conditions were identical. Those details are not reported in the registry record.
What can be concluded from a p-value or a confidence interval?
In general, a p-value assesses how compatible data are with a specified statistical model and null hypothesis; it is not the probability that a hypothesis is true, nor a measure of clinical importance. A confidence interval conveys a range of estimates compatible with the data and model at a stated confidence level. Both require an estimate and an analysis framework. Neither a p-value nor a confidence interval for the primary endpoint is reported, so no significance or precision claim can be made from the registry record.
Statistical significance and magnitude are separate considerations. A small estimated difference may be precise, or an apparently substantial difference may be uncertain. Interpretation would ordinarily consider the estimated contrast, its interval, the clinical or pharmacokinetic context, and the study design. Those numerical results and contextual thresholds are not reported in the registry record.
How should planning calculations be read?
The stated sample-size assumptions describe planning illustrations, not observed power. They use a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. In general, such calculations explore how a hypothetical future study might be sized under specified assumptions. They do not show the probability that this completed study detected an effect, and they do not substitute for the observed estimate and uncertainty.
The registry record does not report its own sample-size justification, a protocol rationale, or an inferential analysis plan. It is not possible to determine whether the planning assumptions match the study’s original design decisions. The posted record also lists 0 analyses, so there is no registry-reported analytical output to connect to the endpoint definition.
What is unknown about the analysis?
The record does not state the analysis population, handling of missing concentration samples, rules for anomalous measurements, treatment of measurements below quantification limits, or whether analysis was adjusted for other characteristics. It does not describe whether parent drug and metabolites were analyzed separately or jointly. These are consequential details for pharmacokinetic interpretation, especially when profiles are sampled repeatedly. They should not be inferred from the sampling schedule alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists Cmax as the primary outcome and lists Tmax and AUC0-t as secondary outcomes. It also records 3 outcome measures overall and identifies BIA 2-194, BIA 2-195, and oxcarbazepine as metabolites of BIA 2-093. Multiple outcomes and analytes can create multiple opportunities to examine patterns. In general, multiplicity refers to the statistical consequences of making several comparisons or tests; without a stated plan, the reader cannot determine whether or how it was addressed.
The registry record does not report a multiplicity adjustment, a prespecified hierarchy of tests, or a statistical analysis plan. It does not explain whether primary and secondary outcomes were analyzed at the same time points or how comparisons across the parent compound, metabolites, dosing periods, and age groups were handled. The listed outcome schedule alone does not establish which comparisons were planned for inference.
Missing-data handling is also not reported in the registry record. The sampling schedule is extensive, but the record does not state whether every scheduled sample was collected, how unavailable or unusable samples were handled, or whether any imputation was used. It does not report outcome-specific analysis populations or explain whether all enrolled subjects contributed to every summary.
In general, missing concentration measurements can affect a profile if their absence is related to concentration, timing, or participant characteristics. The scale and direction of any such effect cannot be assessed without information about missingness and the analysis method. The registry’s count of 0 analyses and absence of numerical outcome results leave these questions unresolved; no particular missing-data or multiplicity procedure should be assumed.
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 |
|---|---|---|---|
| Elderly Subjects | 1 | 14 | 7.1% |
| Young Subjects | 0 | 16 | 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 |
|---|---|
| Elderly Subjects | 11 of 14 |
| Young Subjects | 11 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Elderly Subjects | Young Subjects |
|---|---|---|---|
| cardiovascular collapse | Cardiac disorders | 1 of 14 | 0 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Elderly Subjects | Young Subjects |
|---|---|---|---|
| Tiredness | General disorders | 8 of 14 | 8 of 15 |
| Headache | Nervous system disorders | 5 of 14 | 4 of 15 |
| Dry mouth | Gastrointestinal disorders | 4 of 14 | 3 of 15 |
| Dizziness | Nervous system disorders | 0 of 14 | 3 of 15 |
| Nausea | Gastrointestinal disorders | 2 of 14 | 1 of 15 |
| Concentration impaired | Nervous system disorders | 1 of 14 | 1 of 15 |
| Diarrhoea | Gastrointestinal disorders | 1 of 14 | 1 of 15 |
| Itching | Skin and subcutaneous tissue disorders | 1 of 14 | 1 of 15 |
| Exanthema | Skin and subcutaneous tissue disorders | 1 of 14 | 1 of 15 |
| Drowsiness | Nervous system disorders | 0 of 14 | 1 of 15 |
Serious events with the highest arm-level rate: cardiovascular collapse (7.1%).
The registry reports serious adverse events for the elderly and young subject groups separately. For elderly subjects, the serious-event figures are 1 affected among 14 at risk. For young subjects, the figures are 0 affected among 16 at risk. The record also lists other adverse events for 11 of 14 elderly subjects and 11 of 15 young subjects. These are descriptive counts from the registry, not randomized comparative estimates.
The difference between the at-risk counts in the other-adverse-event entries and the young group description means those figures should be read using the denominators stated for the relevant event category, rather than assuming the same denominator for every safety outcome. The registry does not report why the young-subject other-event denominator is 15.
Cardiovascular collapse is listed among the top serious terms at 7.1%. The registry entry does not provide enough context to establish the event’s group attribution or how that percentage was calculated. Death counts are not reported in the registry record.
These entries do not establish a causal relationship between BIA 2-093 and an event, nor do they support a controlled safety comparison. The study was non-randomized, and the record does not provide event timing, severity details beyond the serious-event categorization, exposure-adjusted rates, or an analysis of comparative risk. The figures should be treated as registry-reported safety counts, with those limitations in mind.
12. What the Result Does, and Does Not, Mean
The study addresses a pharmacokinetic question about age and the concentration profile of BIA 2-093 and its active metabolites. Its stated design compares healthy elderly subjects aged 65 years or more with healthy young subjects aged between 18 and 40 years. Both groups were scheduled to receive the same single-dose and repeated-dose regimen, and Cmax was designated as the primary endpoint.
What the registry record does not establish is the observed size or direction of any age-related difference. Numerical results for Cmax, Tmax, AUC0-t, or the metabolites are not reported in the registry record. There are no posted estimates or intervals in the record to show how precisely the groups’ concentration profiles were characterized. A study objective and measurement schedule are not evidence of a particular result.
Even if concentration differences were reported, pharmacokinetic findings would describe drug exposure, not by themselves establish a clinical benefit or harm. Cmax is not a direct measure of seizure outcomes, and the record does not report a clinical efficacy endpoint. The healthy-subject description also differs from a study of people receiving treatment for epilepsy.
The non-randomized design limits causal interpretation of age-group contrasts. The record does not report adjustment for other group differences, analysis populations, or missing-data methods. Consequently, an unadjusted difference, if encountered in another source, should not automatically be attributed to age alone. The registry record itself contains no numerical primary analysis on which to base such an interpretation.
Planning calculations based on an observed effect are illustrations for future-study sizing under stated assumptions. They are not observed power and do not fill the gap left by unreported outcome results. The useful conclusion from this record is therefore about study scope and methods: it documents a completed Phase 1 pharmacokinetic study, but not the numerical evidence needed to assess its primary comparison.
13. Why This Trial Matters Statistically
This trial is statistically relevant because it makes the distinction between a pharmacokinetic study and a clinical efficacy comparison clear. Its primary outcome, Cmax, is a continuous concentration measure collected at scheduled times. The endpoint can describe peak exposure, while Tmax and AUC0-t address timing and exposure across the measurable interval. Those summaries answer related but different questions.
The age-based, non-randomized parallel design also illustrates why design matters when interpreting a group contrast. The groups receive the same stated regimen, but age is not randomly assigned. Statistical adjustment can sometimes address measured differences, yet the registry does not report whether adjustment was used or what characteristics were considered. The design label alone cannot guarantee that an age-group contrast isolates age.
The record includes a detailed sampling schedule but does not provide endpoint estimates or analysis results. This distinction matters: extensive measurement plans do not communicate the effect’s magnitude or precision. Readers need numerical summaries, a clearly defined analysis population, and an account of uncertainty to evaluate the evidence, and these are not reported in the registry record.
The record also lists several pharmacokinetic outcomes and metabolites. In general, interpretation across multiple measurements benefits from a prespecified analysis strategy, since selective attention to some results can distort the overall picture. The registry does not report such a strategy or any multiplicity handling.
Finally, planning illustrations should be kept separate from study findings. Assumptions based on a fraction of an observed effect can inform hypothetical future sample-size planning, but they are not a measure of the completed study’s observed power. This record is a useful example of why design, measurement, analysis, and result reporting must be considered together.
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 most consequential limitation of the registry record for statistical interpretation is the absence of numerical results for the primary endpoint. Although Cmax and its measurement schedule are described, group means, standard deviations, contrasts, confidence intervals, and test results are not reported in the registry record. The magnitude and precision of the primary finding therefore cannot be assessed.
The study is non-randomized, with groups formed by age. This is appropriate to describe as an age-group comparison, but it does not provide randomized protection against differences between the groups. The registry does not report baseline characteristics or adjustment methods, so potential confounding cannot be evaluated from this record.
The study includes a single dose and a repeated-dose phase, with scheduled sampling at several time points and trough measurements. The record does not report the number of usable samples at each time, how missing or below-quantification measurements were handled, or which analysis population was used. These details are important for interpreting concentration summaries over time.
The registry identifies metabolites and secondary pharmacokinetic outcomes but does not report how they were analyzed, whether comparisons were prespecified, or how multiple analyses were handled. It also does not report a statistical analysis plan or the study’s own sample-size justification. The planning assumptions listed for illustrations should not be taken as the original design rationale.
Safety entries are descriptive, and the registry does not provide enough detail to support a causal or randomized comparison. The record also does not explain the different at-risk denominator for other adverse events in young subjects or the context for the serious-event term listed at 7.1%. These limitations apply to interpretation of the registry record, not necessarily to information that may exist outside it.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Single-dose and Steady-state Pharmacokinetics of BIA 2-093 and Its Metabolites — NCT02172755.
- Registry record last updated 2017-05-19; status last verified 2017-04.
- Results first posted 2014-12-31.
- 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
NCT02172755 is a completed Phase 1, non-randomized, unmasked, parallel study sponsored by Bial - Portela C S.A. It examined the pharmacokinetic profile of BIA 2-093 and its active metabolites in healthy elderly and young subjects. The elderly group included 14 subjects aged 65 years or more, and the young group included 16 subjects aged between 18 and 40 years.
Both groups were scheduled to receive a single 600 mg dose followed by 600 mg once daily for 8 days, with the repeated-dose phase beginning 96 hours after the single dose. Cmax was the primary outcome; Tmax and AUC0-t were listed as secondary outcomes. The registry describes a detailed concentration-sampling schedule but reports 0 analyses and no numerical primary-endpoint results.
The record supports a description of the study question and design, but it does not allow assessment of the size or precision of an age-related pharmacokinetic difference. Its non-randomized structure and unreported analysis details further limit interpretation of any group contrast.