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 Effect of BIA 9-1067 on the Pharmacokinetics of Repaglinide (NCT01536366), a randomized phase 1 study. The primary outcome is Cmax - Maximum Observed Plasma Concentration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01536366 |
| Phase | Phase 1 |
| Condition | Parkinson Disease |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 27 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bial - Portela C S.A. |
| Results posted | Yes |
2. Clinical Question
Population
The official title describes healthy volunteers, and the record lists an enrollment of 27. Parkinson Disease is also listed under conditions. The record does not explain this difference, so the listed condition should not be taken as proof that the participants had Parkinson disease.
Intervention
The intervention was BIA 9-1067 given with repaglinide during one study period. The stated purpose was to investigate CYP2C8 inhibition by BIA 9-1067. Dose details and the schedule for each drug are not reported in the registry record.
Comparator
The comparator period involved repaglinide without BIA 9-1067. Participants were assigned to one of two orders: combination first and repaglinide alone second, or repaglinide alone first and the combination second.
Primary question
The primary endpoint was Cmax, the maximum observed plasma concentration of repaglinide. The registry record identifies this measure but does not report the group or period values, or a comparative estimate. It therefore does not establish from the posted results how Cmax differed between the treatment conditions.
The statistical question is whether repaglinide’s observed maximum plasma concentration differed between the period in which it was given with BIA 9-1067 and the period in which it was given alone. In a crossover study, the same participant can contribute observations under both conditions. This can help make a comparison less dependent on differences between people, provided the analysis accounts for the paired structure and the study’s period and sequence features.
Here, the registry record describes the two treatment orders, but does not report a numerical comparison or analysis method. It also does not report a conclusion about the size, precision, or statistical significance of any difference. The posted record therefore lets readers identify the intended question and study arrangement, but not answer the pharmacokinetic comparison from outcome estimates.
3. Trial Design
This was a Phase 1, randomized, open-label crossover study. The record lists an enrollment of 27 and describes two treatment sequences. In one sequence, participants received BIA 9-1067 with repaglinide during Period 1 and repaglinide during Period 2. In the other, they received repaglinide during Period 1 and the combination during Period 2. The sequence allocation was randomized; masking is listed as none.
The crossover structure means that the planned comparison is between treatment conditions experienced in different periods, rather than simply between two groups that each remain on one treatment. The order is reversed for the two sequences. This arrangement can support a within-participant comparison, but interpretation depends on details such as period effects, possible carryover, and how paired observations were analysed. Those protocol and analysis details are not reported in the registry record.
The official title says the study involved healthy volunteers, while Parkinson Disease appears in the conditions list. The record does not resolve this inconsistency. It lists BIA 9-1067 and repaglinide as the interventions but does not report doses, administration instructions, washout interval, eligibility criteria, or the actual number of participants completing each period.
The study is marked completed. Its recorded start was 2009-06 and its primary completion was 2009-07. These registry entries describe the planned and recorded study structure; they do not, by themselves, indicate what the outcome estimates were. Although the posted page includes tables, plots, and a sample-size section, no numerical Cmax comparison or analysis result is 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.
Overall Study
| Stage | Group 1 | Group 2 |
|---|---|---|
| STARTED | 14 | 13 |
| BIA 9-1067 + Repaglinide | 14 | 10 |
| Repaglinide | 14 | 13 |
| Follow-up | 13 | 9 |
| COMPLETED | 1 | 9 |
| NOT COMPLETED | 13 | 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 | Group 1 | Group 2 | Total |
|---|---|---|---|---|
| Participants analysed | 14 | 13 | 27 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 14 | 13 | 27 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 7 | 6 | 13 |
| Sex: Female, Male: Male | Participants | 7 | 7 | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Cmax - Maximum Observed Plasma Concentration, measured over pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | ng/mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is Cmax, defined as the maximum observed plasma concentration. It is a continuous pharmacokinetic measure, reported in ng/mL, with the mean and standard deviation identified as the summary parameters. The stated sampling schedule runs from pre-dose through 24 h post-dose, with measurements at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose.
In general, Cmax summarizes the highest measured concentration in a dosing profile. It is used in pharmacokinetic studies because it describes peak exposure, while other measures can describe timing or overall exposure. The registry also lists Tmax, AUC0-t and AUC0-∞ as secondary outcomes. Those measures address different features of the concentration-time profile; Cmax is not a substitute for them.
The listed time points describe when samples were scheduled, not the results at those times. The record does not provide the observed means or standard deviations, a treatment contrast, or a confidence interval for Cmax. It also does not report how the maximum was selected when measurements were taken at multiple times. Readers can therefore understand what the endpoint was intended to measure, but cannot assess its observed magnitude or precision from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s stated pharmacokinetic question and its randomized crossover arrangement. It identifies Cmax as the primary outcome and specifies the unit, summary type, and sampling schedule. It also names three secondary pharmacokinetic outcomes: Tmax, AUC0-t and AUC0-∞. These details clarify what was intended to be measured, but they are not outcome findings.
No numerical Cmax values or comparative estimate are reported in the registry record. The record also reports zero analyses. Consequently, there is no posted estimate to describe as a higher or lower concentration, no interval showing the precision of a comparison, and no p-value with which to assess compatibility with a null hypothesis. The record does not report the means, standard deviations, number of evaluable participants for Cmax, or the analysis population. These quantities are not reported in the registry record.
General statistical context: an estimated treatment contrast describes the observed difference between conditions, while a confidence interval conveys the range of values reasonably compatible with the data and analysis. A narrow interval would indicate greater precision than a wide interval. Neither an estimate nor an interval is available, so the precision and direction of any Cmax comparison cannot be assessed. A planned endpoint and a biologically motivated study question do not establish the result.
The crossover design matters to interpretation. A comparison that uses each participant’s observations under both conditions should account for the paired structure. If a treatment-period comparison were instead analysed as if observations were independent, it could fail to use the design appropriately. The record does not say which analysis was used, whether a paired model was fitted, or whether period and sequence were considered. These omissions prevent a statistical reconstruction of the intended treatment comparison.
The study’s safety figures are separate from the pharmacokinetic endpoint. Serious adverse events are recorded as zero in both listed treatment groups, while other adverse events are reported for participants in both groups. These counts do not provide an estimate of Cmax and should not be used to infer a pharmacokinetic effect. Nor do the safety figures alone describe the full safety profile: definitions, event details, timing, and exposure periods are not reported in the registry record.
The sample-size section should be read as a planning illustration, not as evidence about this study’s observed statistical power. Its stated assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with a target effect defined as a fraction of the observed effect. The registry record does not report the underlying observed effect or the trial’s own sample-size justification. The planning illustrations therefore cannot fill the gap in the posted outcome results or establish what the trial could detect under its actual design.
In sum, the record supports a description of the question, endpoints, treatment sequence, and recorded adverse-event counts. It does not support a conclusion about the size, direction, or precision of the Cmax comparison. That distinction is central: a study design and endpoint description are not substitutes for posted estimates and their uncertainty.
9. Statistical Methods Explained
The registry record describes a continuous primary outcome summarized by a mean and standard deviation. It does not report the statistical method used to compare treatment conditions. The explanations below are general statistical context, not a description of analyses confirmed to have been performed in this study.
What the mean and standard deviation describe
For a continuous measure such as Cmax, the mean summarizes the average observed value in a set of measurements. The standard deviation describes how dispersed individual measurements are around that mean. They answer different questions: the mean describes location, while the standard deviation describes variability among observations. Neither alone gives the uncertainty in a treatment comparison. To assess the comparison, readers need an estimate of the contrast and an appropriate measure of its precision, such as a confidence interval.
The registry identifies the mean and standard deviation as the endpoint parameters, but it does not post their values. It also does not report a treatment contrast, standard error, confidence interval, or test result. A reader should not infer any of these from the endpoint definition or from the fact that the study was randomized.
Why the crossover structure matters
In general, crossover data have a within-participant structure: the same person may contribute a measurement under each treatment condition. The two measurements from one participant are usually related, so a suitable comparison should account for that pairing. Analyses can use within-person differences or a model that represents the repeated observations. The exact choice depends on the design, endpoint distribution, and prespecified analysis.
The posted sequence descriptions show that treatment order was reversed between groups. This makes period and sequence relevant considerations in a crossover study. A period effect is a difference associated with when a measurement is taken, apart from the treatment condition. Carryover refers to an effect of an earlier treatment that persists into a later period. In general, a washout interval and other design details may be relevant to assessing carryover, but the interval and any carryover assessment are not reported in the registry record. The record likewise does not say whether period or sequence effects were assessed or how they were handled.
It would be inappropriate to claim that a paired model, a particular test, or a particular adjustment was used. The registry record reports no analyses, and the analysis plan is not reported in the registry record. The design description alone cannot identify the method actually used for any sponsor analysis.
Precision and uncertainty
General statistical context: an estimate is a summary of the data, and a confidence interval expresses uncertainty around that estimate under the assumptions of the method. Greater precision is reflected by a narrower interval, while a wider interval leaves more uncertainty about the magnitude of the effect. A p-value addresses compatibility with a specified null model, but does not express the size or clinical importance of an effect. These concepts are useful when results are available; they cannot be applied to a treatment comparison that is not posted.
For this record, no confidence interval or p-value is listed. The absence of these results does not mean that the true comparison is zero, nor does it establish that a difference exists. It means the registry record does not report the information needed to assess the estimate and its uncertainty.
Distributional assumptions and transformed measures
General context: continuous pharmacokinetic measurements can have distributions for which a mean-based normal model is not a good description. Analysts may consider transformations or models suited to the data, but the choice should be justified by the endpoint, design, and analysis plan. No transformation, distributional assessment, or model specification is reported in the registry record. This page therefore cannot state whether the posted analysis used the raw scale, a transformed scale, or another approach.
Over-dispersion is a general concern when observed variability is greater than a model assumes. If a model understates variability, its uncertainty estimates can be too small. A suitable analysis should represent the variation present in the observations. The registry record does not report model diagnostics or variance assumptions, so no claim about over-dispersion or its handling can be made for this study.
Planning illustrations
The sample-size section is a planning illustration based on the observed effect, not the trial’s own design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm. These assumptions describe the illustration, not an analysis performed on the trial data.
General context: a sample-size calculation asks what amount of information might be needed for a chosen effect and assumptions. It is not an observed result, and it should not be described as observed power. The registry record does not report the trial’s sample-size justification, the effect used for its original planning, or the method by which the original enrollment target was chosen. Also, an illustration framed in terms of equal allocation between arms does not, by itself, reproduce every feature of this crossover design.
Because the registry record does not report outcome estimates, the illustration cannot be used to validate or reinterpret a Cmax result. Its role is limited to showing how planning quantities depend on the stated assumptions. The underlying observed effect and the numerical planning outputs are not described in this record’s results details.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome, Cmax, and three secondary outcomes: Tmax, AUC0-t and AUC0-∞. Cmax is described across a sampling schedule extending from pre-dose to 24 h post-dose. The record does not state whether the multiple scheduled measurements were treated as repeated observations, used to derive a single maximum, or analysed in another way. It also does not identify which outcome comparisons, if any, were formally tested.
General statistical context: when several outcomes, time points, or treatment contrasts are examined, the chance of at least one apparently unusual result can increase. A statistical analysis plan may specify a primary comparison, a testing hierarchy, or an adjustment for multiple comparisons. Whether such a strategy was used is not reported in the registry record. The presence of several listed outcomes does not establish that multiplicity was addressed or ignored.
The registry record reports zero analyses and does not provide comparative estimates, confidence intervals, p-values, or results for the secondary outcomes. It does not identify an analysis population, a missing-data method, or how many participants contributed usable measurements to each outcome. Reasons for missing measurements, withdrawals, and completion of each treatment period are also not reported in the registry record.
In general, missing data can affect both the precision and the interpretation of a treatment comparison, especially when the reason observations are missing is related to treatment or outcome. The appropriate approach depends on how much data are missing, why they are missing, and the trial design. Without participant flow and analysis details, readers cannot assess whether the available observations represent all randomized participants or how missingness was handled. No particular missing-data method should be attributed to this study on the basis of the registry record.
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 |
|---|---|---|---|
| BIA 9-1067 + Repaglinide | 0 | 24 | 0.0% |
| Repaglinide | 0 | 27 | 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 |
|---|---|
| BIA 9-1067 + Repaglinide | 7 of 24 |
| Repaglinide | 8 of 27 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BIA 9-1067 + Repaglinide | Repaglinide |
|---|---|---|---|
| Hypotension | Vascular disorders | 1 of 24 | 1 of 27 |
| Presyncope | Cardiac disorders | 1 of 24 | 0 of 27 |
| Nausea | Gastrointestinal disorders | 0 of 24 | 1 of 27 |
| Vomiting | Gastrointestinal disorders | 0 of 24 | 1 of 27 |
| Influenza like illness | General disorders | 1 of 24 | 0 of 27 |
| Cystitis | Infections and infestations | 0 of 24 | 1 of 27 |
| Oral herpes | Infections and infestations | 1 of 24 | 0 of 27 |
| Otitis externa | Infections and infestations | 0 of 24 | 1 of 27 |
| Pharyngitis | Infections and infestations | 0 of 24 | 1 of 27 |
| Vulvovaginal candidiasis | Infections and infestations | 0 of 24 | 1 of 27 |
The registry lists serious adverse events for two treatment groups. For BIA 9-1067 + Repaglinide, the record gives 0 serious adverse events among 24 participants at risk. For Repaglinide, it gives 0 among 27 participants at risk. The record also reports other adverse events for 7 of 24 participants in the combination group and 8 of 27 in the repaglinide group.
These are descriptive counts from the registry record. The denominators differ, and the record does not explain why the numbers at risk differ or how they relate to participants completing each crossover period. The treatment-order descriptions show that participants could receive both conditions in different periods; the safety entries do not explain how exposure time or treatment period was handled when assigning events to groups.
The entries indicate that no serious adverse events were recorded in these listed groups, not that the study had no adverse events. The other-event figures are not broken down by event type or severity in the information. Death counts are not reported in the registry record. The event definitions, observation window, and method for attributing events to a treatment are also not reported, so these counts should not be interpreted as a complete or adjusted comparison of safety.
12. What the Result Does, and Does Not, Mean
This record is useful for identifying a focused pharmacokinetic question: whether the maximum observed plasma concentration of repaglinide differed when repaglinide was given with BIA 9-1067 rather than alone. It documents a randomized, open-label crossover arrangement, the two treatment orders, the primary endpoint, and the listed secondary outcomes. Those details establish the study’s stated structure and measurement plan.
The record does not report the outcome estimates needed to determine what the study observed. In particular, there is no posted numerical Cmax result or comparison, no confidence interval, and no p-value. The direction and magnitude of any difference, and the precision of that estimate, are therefore not reported in the registry record. This is not evidence that the comparison found no difference; it is a limit on what can be concluded from the posted information.
General statistical context: the result of a study is not captured by its design label, sample size, or stated objective. Interpretation depends on the measured data, the analysis, and the uncertainty around the estimate. In a crossover study, it also depends on how within-participant observations and period features are handled. Those analysis details are not reported, so the reader cannot assess whether the analysis reflects the design.
The safety entries provide a separate, limited description: zero serious adverse events are recorded in each group, and other adverse events are listed for participants in both groups. These counts do not answer the Cmax question and should not be treated as a substitute for the pharmacokinetic results. Details needed for a fuller safety interpretation are not reported in the registry record.
The most defensible reading is consequently narrow. The record describes what the investigators intended to compare and some event counts, but does not provide the comparative pharmacokinetic results. The posted data as do not establish whether Cmax changed, by how much, or with what statistical precision.
13. Why This Trial Matters Statistically
This study illustrates how a crossover design frames a pharmacokinetic comparison. Instead of assigning each participant to remain in just one condition, the two recorded sequences place participants in both treatment conditions in different periods. In general, this can allow a comparison that uses within-participant information, while making the handling of pairing, period, sequence, and possible carryover important to interpretation.
It also highlights the difference between naming an endpoint and reporting its results. The registry specifies Cmax, its unit, the summary parameters, and a detailed sample schedule. It names additional measures of timing and overall exposure. Yet the record reports no analyses or numerical comparisons. A clearly defined endpoint is important, but a definition cannot show the size or precision of an observed effect.
The record is also a useful reminder that trial descriptions can contain inconsistencies or gaps. The official title refers to healthy volunteers, while Parkinson Disease is listed as a condition. The treatment orders are given, but dose, washout, analysis, and participant-flow details are not. A careful statistical reading distinguishes what the record explicitly states from what it leaves unresolved rather than filling those gaps with assumptions.
Finally, the planning illustrations have a different purpose from trial results. They show how sample-size planning can depend on assumptions about the target effect and analysis. They are not an account of the trial’s original justification and are not observed power. Keeping design, analysis, outcome estimates, safety counts, and planning calculations separate helps readers avoid treating one type of information as evidence for another.
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 principal limitation for interpretation is that the registry record does not report numerical results for the primary Cmax endpoint. It provides no treatment contrast, uncertainty interval, or test result. Although the endpoint and sampling schedule are described, no observed means or standard deviations are available. The comparative pharmacokinetic finding therefore cannot be evaluated from the record.
The analysis is also not described. The record does not report whether the comparison accounted for within-participant pairing, period, sequence, or possible carryover. It does not provide the analysis population, the number of participants with outcome data, participant flow through both periods, or methods for missing observations. The washout interval and relevant protocol details are not reported in the registry record.
There is a population-description ambiguity: the official title refers to healthy volunteers, while Parkinson Disease is listed under conditions. The record does not explain the relationship between those entries. It also does not report the doses or detailed administration schedule. These gaps limit a reader’s ability to characterize the study population and treatment exposure beyond the stated descriptions.
The safety information is limited to group-level counts. Event types, event timing, exposure periods, death counts, and the basis for the differing numbers at risk are not explained. The sample-size illustrations do not replace a trial-specific justification, which is not reported in the registry record. Together, these limitations mean that the page can describe the intended comparison and recorded event counts, but cannot independently assess the outcome estimates, analysis assumptions, or completeness of reporting.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of BIA 9-1067 on the Pharmacokinetics of Repaglinide — NCT01536366.
- Registry record last updated 2015-08-20; status last verified 2015-07.
- Results first posted 2015-08-20.
- 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
The registry record describes a completed Phase 1 randomized, open-label crossover study titled Effect of BIA 9-1067 on the Pharmacokinetics of Repaglinide in Healthy Volunteers. It lists an enrollment of 27 and two treatment sequences that reverse the order of BIA 9-1067 plus repaglinide and repaglinide alone. The stated purpose was to investigate CYP2C8 inhibition by BIA 9-1067.
The primary outcome was Cmax, reported as a mean and standard deviation in ng/mL, with sampling from pre-dose through 24 h post-dose. Secondary outcomes were Tmax, AUC0-t and AUC0-∞. The record reports zero analyses and does not report a numerical primary-outcome comparison. Serious adverse events are recorded as zero in both listed groups; other adverse events are reported for 7 of 24 and 8 of 27 participants, respectively. The population entry is unresolved: the title refers to healthy volunteers, while Parkinson Disease is listed under conditions.