Absorption, Distribution, Metabolism and Excretion of [14C]-Labeled BIA 9-1067 and Metabolites: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Absorption, Distribution, Metabolism and Excretion of [14C]-Labeled BIA 9-1067 and Metabolites (NCT01515891), a na phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax).

2. Clinical Question

This is a descriptive pharmacokinetic study, not a randomized comparison of treatments. Its stated purpose was to determine the absorption, metabolism, and excretion of BIA 9-1067. The named secondary outcomes were time to maximum plasma concentration (Tmax), area under the plasma-concentration time curve until the last quantifiable sampling point (AUC0-t), and area under the curve with extrapolation to infinity (AUC0-∞).

The registry record lists four enrolled participants. It does not report numerical results for Cmax or the named secondary outcomes, so the clinical question cannot be answered from the posted outcome results. The record also does not describe a patient outcome or a comparison of clinical benefit. Its focus is the disposition of the radiolabeled drug and its metabolites after a single oral administration.

3. Trial Design

The registry describes a phase 1, open-label, single-group study with no masking and no randomized allocation. It lists enrollment of 4 and an intervention consisting of BIA 9-1067. The official title specifies a single-dose oral administration in healthy male subjects; the intervention description specifies 100 mg of BIA 9-1067 labeled with 90 µCi (3.33 MBq) of [14C].

There is no comparator arm, so this design does not estimate a between-group treatment contrast. Instead, its stated purpose is to characterize absorption, metabolism, and excretion following the administration. The registry describes collection of whole blood samples for total radioactivity, plasma samples for total radioactivity, and plasma samples for analysis of BIA 9-1067 and its metabolites.

The listed primary outcome is mean maximum plasma concentration (Cmax), with standard deviation as the dispersion measure and ng-eq/mL as the unit. The listed timeframe includes a pre-dose measurement and post-dose sampling through 264 hours. The registry also names Tmax, AUC0-t, and AUC0-∞ as secondary outcomes. However, numerical outcome values are not reported in the registry record.

The registry lists Parkinson Disease as a condition, while the official title describes healthy male subjects. It does not explain this difference. The record identifies the study as completed and lists its phase, design, intervention, and planned outcome measures, but does not report a detailed protocol, eligibility criteria, or analysis population. Those details 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.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Plasma Concentration (Cmax), measured over 24 hours:pre-dose and 1, 1.75, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, and 264 hours post-dose.

The primary endpoint is maximum plasma concentration (Cmax), reported as a mean in ng-eq/mL, with standard deviation identified as the measure of dispersion. Cmax represents the highest measured concentration over the relevant sampling period. In pharmacokinetic work, it is used to describe the peak concentration observed after administration; it is not, by itself, a measure of clinical benefit or harm.

The registry describes measurements involving total radioactivity in whole blood and plasma, as well as BIA 9-1067 and its metabolites in plasma. The listed sampling schedule begins with a pre-dose sample and includes post-dose collections through 264 hours. This schedule gives context for the concentration measurement, but the registry does not report the numerical Cmax result or clarify which analyte-specific result is presented as the primary outcome.

Mean and standard deviation summarize different features of a continuous measure. The mean describes its average, while the standard deviation describes how spread out individual observations are around that average. General statistical interpretation requires both the underlying results and their context; neither is available as a numerical primary-endpoint result in the registry record. Accordingly, the endpoint’s purpose can be described, but its observed magnitude and variability cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary outcome as a continuous measure summarized by a mean and standard deviation. It identifies Cmax as the measure, ng-eq/mL as its unit, and specifies sampling from pre-dose through 264 hours after dosing. These are outcome and measurement details. The registry does not report the numerical estimate, its standard deviation, or an inferential analysis.

What does a mean describe?

General statistical explanation: a mean is an average across observations. In this setting, it would summarize the participants’ measured maximum plasma concentrations. The mean alone does not show whether individual observations were similar or widely dispersed. The standard deviation is a descriptive measure of that spread. It does not directly express the precision of the mean, which depends on the amount of information and the analysis assumptions.

How should a confidence interval be understood?

General statistical explanation: a confidence interval presents a range of values compatible with an estimate under a specified statistical procedure. Its width communicates precision: a narrower interval indicates greater precision under that procedure, while a wider interval indicates less. This is not the same as a range containing every participant’s observed value. No confidence interval is reported for the listed outcomes, so precision cannot be quantified from the registry record.

What would a p-value add?

General statistical explanation: a p-value is a measure calculated under a particular statistical model and null hypothesis. It does not state the probability that a hypothesis is true, nor does it measure the size or practical importance of an effect. In a single-group pharmacokinetic description, the relevant estimand and any null hypothesis would need to be specified before a p-value could be interpreted. No p-value or analysis is listed in the registry record.

Why does the study design shape interpretation?

General statistical explanation: a single-group study measures participants who received the intervention but has no concurrent control group for estimating a between-group difference. Open-label status means masking is not identified; the registry explicitly lists masking as none. These design features do not prevent descriptive measurement, but they define what kinds of comparisons the study can support. In this record, the stated goal is absorption, metabolism, and excretion characterization rather than a randomized treatment contrast.

What do the pharmacokinetic measures represent?

General statistical explanation: Cmax describes the maximum concentration measured over a sampling period. Tmax describes the time at which the maximum concentration is reached. AUC summarizes concentration over time; AUC0-t covers the interval to the last quantifiable sampling point, while AUC0-∞ includes extrapolation to infinity. These measures answer different descriptive questions. Their interpretation depends on the analyte, collection schedule, and analysis procedures. The registry names the measures but does not report their numerical results or a detailed method for deriving them.

How should planning illustrations be treated?

General statistical explanation: a sample-size planning illustration asks how many participants might be needed under stated assumptions to detect a target effect. It is not a measure of observed power, and it does not replace the actual outcome estimate or its uncertainty. The record’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. Those assumptions concern a hypothetical two-arm planning calculation and do not turn this single-group study into a randomized comparison. The registry does not report a trial-specific sample-size justification.

Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. When that happens, model-based uncertainty estimates can be too small if the extra variability is ignored. The registry record does not identify an over-dispersion assessment or a model used for the listed outcomes, so no such adjustment can be evaluated.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("BIA 9-1067")
n   <- c(4)
m   <- c(482.98)
sp  <- c(265.26)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  BIA 9-1067  4  482.980  265.260  60.892  905.068

11. Multiplicity, Missing Data and Analysis Populations

The registry names a primary outcome and three secondary outcomes, but a multiplicity strategy is not reported in the registry record. General statistical explanation: when several outcomes or hypotheses are tested, the chance of at least one false-positive result can increase if each is assessed without accounting for the collection of tests. A prespecified strategy can define which outcome is primary, how secondary findings are interpreted, and whether adjustments are used. The registry identifies the outcome roles but does not report a testing hierarchy or adjustment method.

Missing-data methods are not reported in the registry record. The listed sampling schedule does not establish whether every planned sample was collected, whether any measurement was unusable, or how missing observations were handled. The numerical outcome results are not reported, so the extent of missingness cannot be assessed from the posted results.

The analysis population is also not reported in the registry record. Enrollment is listed as 4, but the record does not state how many participants contributed to each outcome analysis or define an analysis set. It would be inappropriate to assume that every enrolled participant was included in every pharmacokinetic summary.

The registry lists zero analyses. It therefore supplies no reported model, estimation procedure, or inferential results for the primary or secondary outcomes. These omissions limit assessment of multiplicity, missing-data handling, and analysis-population choices. They do not establish that such procedures were absent from study conduct; they mean that they are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 4 participants at risk for serious adverse events and reports 0 affected. For other adverse events, it lists 4 participants at risk and 3 affected. These are participant counts in the registry’s safety fields, not rates recalculated. The record does not list serious adverse-event terms, and the field for top serious terms is empty.

Serious and other adverse events are separate categories in the posted safety information. The counts should not be combined or treated as a complete account of every event unless the registry provides that detail. The record does not report event descriptions for the other adverse events, their timing, severity, duration, or relationship to the intervention. Deaths are not reported in the registry record.

General statistical explanation: a count of affected participants gives limited information without event definitions, follow-up details, and the underlying participant-level context. The safety entries do not establish whether an event was caused by the intervention. They also do not provide comparative safety evidence, because the study has a single group and no comparator. These figures should therefore be read as registry-reported counts, not as a causal comparison or a complete safety profile.

13. What the Result Does, and Does Not, Mean

The registry record describes a small, single-group pharmacokinetic study of radiolabeled BIA 9-1067. It identifies the primary measure, Cmax, and names secondary measures intended to describe timing and exposure. It also records the intervention as a single oral dose of 100 mg labeled with 90 µCi (3.33 MBq) of [14C]. These details establish the study’s focus and the measurements it planned to report.

The posted record does not report numerical results for Cmax, Tmax, AUC0-t, or AUC0-∞. It therefore does not show the observed concentration, time-to-maximum, exposure estimates, or variability. The absence of those values means their magnitude and precision cannot be assessed from this record. It should not be interpreted as a zero result or as evidence that no measurements were made.

The design does not include a comparator group or randomized allocation. As a result, the record does not provide a comparative treatment estimate. Its stated purpose is to characterize absorption, metabolism, and excretion, not to test a clinical treatment effect. No conclusion about clinical benefit or harm follows from the listed pharmacokinetic endpoints alone.

The safety entries report no participants with serious adverse events and three participants affected by other adverse events, among four at risk in each category. The record does not provide terms for the serious adverse events, details for the other events, or deaths. These counts are useful as registry entries but cannot support a detailed assessment of event type, timing, or cause.

Overall, the record supports a description of the design, dose, intended pharmacokinetic measures, and limited safety counts. It does not supply the outcome estimates needed to characterize observed pharmacokinetics or their uncertainty. The distinction between a planned measure and a reported result is essential to interpreting what this study record can establish.

14. Why This Trial Matters Statistically

This study is statistically relevant because it illustrates the difference between defining a measurement and reporting its result. The registry specifies Cmax as a continuous primary outcome, identifies a mean and standard deviation as its summary, and names three secondary pharmacokinetic measures. Yet numerical values for those outcomes are not reported in the registry record. A clearly named endpoint is not enough to assess its observed magnitude or precision.

The single-group design also illustrates how study structure determines the estimand. Without a comparator arm, the study does not estimate a randomized between-group contrast. Its stated purpose is descriptive: to assess absorption, metabolism, and excretion after a single oral dose. Statistical interpretation should follow that purpose rather than treating the record as a comparative clinical trial.

The record also shows why outcome summaries and analysis details matter together. A mean can describe an average, and a standard deviation can describe spread, but readers need the actual values and clear information about the analysis population and handling of missing observations to judge the findings. Those analysis details are not reported in the registry record.

Finally, the safety fields show how counts can be informative yet limited. The record reports 0 participants with serious adverse events and 3 with other adverse events among 4 at risk. Without event descriptions and follow-up context, those counts remain a narrow summary rather than a complete account of safety. This study is a useful example of why design, outcome definition, numerical reporting, and analysis transparency all contribute to statistical interpretation.

15. 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 main limitation for interpretation is that the registry record does not report numerical results for the primary or secondary pharmacokinetic outcomes. Without those values, the observed concentrations, exposure measures, variability, and precision cannot be assessed. The registry lists zero analyses, so it also does not report inferential results for these measures.

The study has a single group, no randomized allocation, and no comparator. It can therefore be described as a pharmacokinetic assessment, but it does not provide a controlled treatment contrast. Enrollment is listed as 4, which also means the posted record concerns a small participant group; the record does not provide detail on how representative that group is.

The official title describes healthy male subjects, while the registry lists Parkinson Disease as a condition. The record does not clarify this difference. It also does not report detailed eligibility criteria or an analysis population. The intervention and sampling description are present, but the analyte-specific numerical endpoint results are not reported.

Multiplicity procedures, missing-data handling, and a trial-specific sample-size justification are not reported in the registry record. The safety information is limited to participant counts: event descriptions for other adverse events are not given, serious-event terms are not listed, and deaths are not reported. These limitations constrain interpretation of both pharmacokinetic findings and safety, but they should not be read as proof that unreported methods or observations did not exist.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Absorption, Distribution, Metabolism and Excretion of [14C]-Labeled BIA 9-1067 and Metabolites — NCT01515891.
• Registry record last updated 2015-01-09; status last verified 2014-12.
• Results first posted 2015-01-09.
• 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.

19. Record Summary

The registry identifies NCT01515891 as a completed phase 1, open-label, single-group study with enrollment of 4. Its official title describes healthy male subjects receiving a single oral administration of radiolabeled BIA 9-1067. The intervention description specifies 100 mg with 90 µCi (3.33 MBq) of [14C].

The primary outcome is mean Cmax in ng-eq/mL, with standard deviation listed as the dispersion measure. Secondary outcomes are Tmax, AUC0-t, and AUC0-∞. Numerical results for these outcomes are not reported in the registry record, and the record lists zero analyses.

The safety entries report 0 serious adverse events among 4 at risk and 3 participants with other adverse events among 4 at risk. Serious-event terms and deaths are not reported in the registry record. The record lists Parkinson Disease as a condition but does not explain its relationship to the healthy male population described in the official title.