Study to Assess Absolute Bioavailability (ABA) of TAK-906 and to Characterize Mass Balance, Pharmacokinetics (PK), Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Absolute Bioavailability (ABA) of TAK-906 and to Characterize Mass Balance, Pharmacokinetics (PK), Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male Participants (NCT04454918), a na phase 1 study. The primary outcome is Period 1: Absolute Bioavailability Based on Ratio of Dose Normalized Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞ ) for TAK-906.

2. Clinical Question

This is a pharmacokinetic study rather than a trial designed to compare clinical outcomes between treatments. Its central purpose was to characterize how much TAK-906 reaches the circulation after oral dosing relative to intravenous dosing, using plasma exposure as the basis for the comparison. The study also assessed mass balance after oral radioactive [14C]-TAK-906, with urine and feces identified as the collection routes of interest.

The registry lists additional pharmacokinetic outcomes, including maximum observed plasma concentration, time to maximum concentration, exposure through the last quantifiable concentration, the extrapolated portion of exposure, terminal half-life, apparent distribution volume, apparent clearance, and total radioactivity at the end of the infusion. These measures describe different aspects of concentration over time and drug disposition. They do not substitute for a reported primary bioavailability estimate.

The record describes a small study in healthy male participants and does not report a clinical efficacy question. Its design is suited to describing pharmacokinetic properties under the stated study conditions; it does not establish how the findings apply to other populations or treatment settings.

3. Trial Design

The registry classifies NCT04454918 as a Phase 1, single-group study with no masking. Allocation is listed as not applicable. Enrollment was 6, and the condition is listed as healthy volunteers. The study is marked completed. Its listed start date is 2020-07-30 and its primary completion date is 2020-09-30.

The procedures covered two related objectives. In Period 1, the study assessed absolute bioavailability using a single oral 50 mg TAK-906 capsule and a single intravenous 100 μg [14C]-TAK-906 microtracer dose. The registry describes pharmacokinetic sampling from pre-dose through multiple post-dose time points up to 96 hours. In Period 2, the study assessed mass balance after a single oral solution dose of 50 mg [14C]-TAK-906, with urine and feces identified as the relevant routes for measuring recovery.

The brief summary describes a 7-day washout between the Period 1 dosing and the Period 2 assessment. Thus, the study involved sequential procedures in the same study group, not independent randomized groups assigned to competing treatments. The registry’s arm descriptions name the dosing regimens, but the primary design is identified as single-group; the arm labels should not be interpreted as evidence of a like-for-like control comparison.

The primary endpoint was defined for TAK-906 in Period 1 as percent absolute bioavailability, expressed as a geometric least squares mean ratio with a 90% confidence interval. The endpoint uses dose-normalized AUC from time zero to infinity. The registry also lists 40 outcome measures, including several pharmacokinetic measures for TAK-906 and metabolite M23. It records no analysis entries. The statistical plan, sample-size justification, and any interim analyses are not reported in the registry record.

The study’s purpose and design are descriptive and pharmacokinetic. The registry does not present an efficacy comparison, a randomized treatment contrast, or a parallel untreated group. Findings from the procedures should therefore be read in the context of the specific doses, routes, sampling periods, and healthy male population described in the 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: Healthy male participants were enrolled in this study to receive TAK-906 capsule followed by radio-labelled TAK-906 intravenous (IV) infusion on Day 1 of Treatment Period 1 and radio-labelled TAK-906 oral solution on Day 1 of Treatment Period 2. There was a 7-day Washout Period between the two periods.

Treatment Period 1 (Day 1)

Washout Period (Day 2 to 8)

Treatment Period 2(Day9[Day1of Period2])

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) Set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile (e.g., exposure to treatment, availability of measurements and absence of major protocol violations). Participants who received the oral dose of TAK-906 50 mg capsules followed by \[14C\]-TAK-906 100 μg \[approximately 1 μCi\], IV infusion in Period 1 were evaluated for this outcome measure.

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: Safety Set included all participants who received at least one dose of the study drug.

6. Primary Endpoint

The registry lists the primary outcome as Period 1: Absolute Bioavailability Based on Ratio of Dose Normalized Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞ ) for TAK-906, measured over Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Treatment Period 1.

The primary endpoint is percent absolute bioavailability of TAK-906 after oral dosing. Bioavailability concerns the proportion of a dose that enters the circulation. The registered calculation compares dose-normalized exposure after oral and intravenous administration, using AUC from time zero to infinity. The intravenous AUC is normalized to a 50 mg dose, and the result is expressed as a geometric least squares mean ratio multiplied by 100.

AUC represents the area under the plasma concentration-time curve. It summarizes measured drug exposure across time rather than describing concentration at only one sampling point. Dose normalization is used because the oral and intravenous administrations differ in dose: comparing exposure in relation to dose makes the routes interpretable on a common basis. The geometric least squares mean is the registered summary measure, and the 90% confidence interval is intended to describe uncertainty around that estimate.

The endpoint is useful for characterizing oral absorption relative to intravenous exposure under the study conditions. It is a pharmacokinetic measure, not a direct measure of clinical benefit or harm. Interpretation depends on the concentration measurements, the exposure estimates, and the analysis population specified for the endpoint.

The registry record describes how the endpoint was defined but does not report its numerical estimate or confidence interval. Consequently, the posted record does not establish the observed absolute bioavailability value or the precision of that estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered endpoint is based on a ratio of dose-normalized exposure. Understanding the components clarifies what the planned statistic measures, while keeping separate the endpoint definition from results that are not reported in the registry record.

What does AUC represent?

AUC is the area under a plasma concentration-time curve. In general, it summarizes exposure over the period represented by the concentration measurements. The primary outcome uses AUC from time zero to infinity, written as AUC∞. Because the full concentration-time profile may not be directly observed at every time, an AUC∞ estimate can include an extrapolated portion after the last quantifiable concentration. The registry lists the percent extrapolated as a secondary outcome, but does not report its result.

Why normalize by dose?

The oral and intravenous doses in Period 1 are different: the oral capsule dose is 50 mg, while the intravenous microtracer dose is 100 μg. Dose normalization expresses exposure in relation to the administered dose so the route-specific exposure estimates can be compared on a common basis. The endpoint description states that the intravenous AUC∞ was normalized to a 50 mg dose. The calculation then forms the oral-to-intravenous dose-normalized exposure ratio and multiplies it by 100 to express percent absolute bioavailability.

This ratio is designed to describe relative systemic exposure after oral versus intravenous administration. It is not simply a comparison of raw concentrations, and it is not a direct measure of clinical effects. Its interpretation rests on the study’s pharmacokinetic measurements and the calculation specified in the endpoint definition.

What do the geometric least squares mean and confidence interval convey?

The primary parameter is a geometric least squares mean. In general, geometric summaries are useful for quantities that are positive and may be analyzed on a logarithmic scale. A least squares mean is a model-based summary rather than necessarily a raw arithmetic average. The registry identifies this parameter and a 90% confidence interval, but it does not report the model details or the resulting estimate.

In general, a confidence interval describes uncertainty around an estimated quantity under the analysis assumptions. It is not a guarantee that the true value lies within the interval, nor is it a measure of the clinical importance of a result. Without the numerical estimate and interval, neither the magnitude nor the precision of the primary finding can be assessed from the registry record.

How do the other pharmacokinetic measures complement AUC?

The registry lists several secondary outcomes for TAK-906 and metabolite M23 after oral administration. Cmax is the maximum observed plasma concentration, while Tmax is the time at which that maximum is reached. AUClast summarizes exposure from time zero through the last quantifiable concentration. AUC%Extrap describes the proportion of AUC∞ that is extrapolated. Terminal disposition half-life describes the terminal phase of the concentration decline.

The record also lists apparent volume of distribution during the terminal elimination phase and apparent total plasma clearance for TAK-906. These are pharmacokinetic parameters derived from concentration and disposition information; the “apparent” labels reflect the stated oral-route parameterization. Ceoi is the plasma total radioactivity concentration at the end of the intravenous infusion. Together, such measures can describe concentration peaks, overall exposure, terminal behavior, and radioactivity after dosing. The registry does not report their numerical results.

Why can over-dispersion matter in count outcomes?

In general, count data may vary more than a simple statistical model expects. This is called over-dispersion, and it can make standard errors or confidence intervals too small if the model does not allow for the extra variability. That general issue may matter in analyses of event counts, but the registry record does not report a count-model analysis for this study. No particular model or adjustment for over-dispersion should therefore be attributed to the investigators.

What is reported about the analysis population?

The primary endpoint population is described as the pharmacokinetic set. It includes participants who complied sufficiently with the protocol and displayed an evaluable pharmacokinetic profile, with examples including exposure to treatment, available measurements, and absence of major protocol violations. The description further identifies participants who received the oral TAK-906 50 mg capsules. This is an eligibility definition, not a report of how many participants were included in the endpoint analysis.

The registry record does not report the actual analysis count, participant-level exclusions, or the treatment of missing or unevaluable measurements. It lists no analysis entries. That absence means the registry record does not supply an analysis result; it should not be taken as evidence that no analysis was performed outside the registry entry.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 40 outcome measures, including the primary bioavailability outcome and multiple pharmacokinetic outcomes. The record does not report a multiplicity procedure, such as an adjustment to account for testing several outcomes, nor does it state how the outcomes were organized into confirmatory and exploratory analyses. The statistical plan is not reported in the registry record. It is therefore not possible to determine from this record how multiplicity was handled or what inferential status was intended for the secondary outcomes.

The primary endpoint description identifies a pharmacokinetic set, defined by sufficient protocol compliance, an evaluable pharmacokinetic profile, and receipt of oral TAK-906 50 mg capsules. The registry does not report the number of participants in that set, participant flow into the analysis, or the reasons any participant might have been excluded. Although enrollment is reported as 6, that value does not establish the endpoint analysis count.

The handling of missing concentration measurements, incomplete profiles, values below quantification, or other missing data is not reported in the registry record. The record also does not state whether any sensitivity analyses were conducted to assess the impact of missing or unevaluable data. These omissions matter because exposure estimates depend on the availability and interpretation of concentration measurements over time.

The registry lists no analysis entries. This describes what is recorded in the registry, not necessarily the full set of work performed by the study team. The outcome count and absence of analysis entries do not establish whether analyses were conducted, how they were adjusted, or whether results were submitted elsewhere.

11. Safety Results

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

Deaths

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 reports serious adverse event counts separately for the two listed dosing groups. In the TAK-906 50 mg plus [14C]-TAK-906 100 μg group, 6 were at risk and 0 were reported with serious adverse events; 0 deaths were reported. In the [14C]-TAK-906 50 mg group, 6 were at risk and 0 were reported with serious adverse events; 0 deaths were reported.

For other adverse events, the record reports 0 affected in the TAK-906 50 mg plus [14C]-TAK-906 100 μg group and 2 affected in the [14C]-TAK-906 50 mg group. These are registry counts, not estimates of comparative risk. The listed groups correspond to study dosing, not randomized parallel arms, and the record does not describe a like-for-like control comparison.

The registry does not list serious adverse event terms. The reported absence of serious events and deaths is limited to the entries and study population represented in the record. It should not be interpreted as evidence that an event could not occur, or as a comparative safety conclusion. The record does not provide further detail about the type, timing, or severity of the other adverse events.

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

The study was designed to characterize TAK-906 pharmacokinetics and mass balance in healthy male participants. Its primary question concerns absolute bioavailability after oral dosing, estimated by comparing dose-normalized AUC∞ following oral and intravenous administration. The registry record supplies the endpoint definition and study procedures but not the numerical primary result. It therefore does not show the observed bioavailability estimate or its confidence interval.

The record also does not report numerical results for the listed secondary pharmacokinetic outcomes or for the Period 2 mass-balance assessment. Without those results, the degree of exposure, the concentration-time profile, the recovery of radioactivity, and the precision of the estimates cannot be described from the registry record.

The safety entries show no reported serious adverse events or deaths in either listed dosing group, and report other adverse events in the [14C]-TAK-906 50 mg group. These counts are descriptive and do not establish a treatment difference. The study has no separate randomized control group, and the registry identifies it as a single-group study.

More generally, pharmacokinetic findings from this study would describe the tested doses and routes under the recorded study conditions. They would not, by themselves, establish clinical efficacy, long-term safety, or how results apply to populations other than the healthy male participants described. Those broader questions are not answered by the endpoint definition or the posted safety counts.

13. Why This Trial Matters Statistically

This trial illustrates how a pharmacokinetic study can compare oral and intravenous exposure to estimate absolute bioavailability. The route comparison is based on AUC∞ normalized for dose, rather than on an unadjusted comparison of the administered amounts. This distinction is important when the objective is to characterize the fraction of an oral dose reaching the circulation relative to an intravenous reference.

The design also connects two different pharmacokinetic aims. Period 1 addresses bioavailability using oral TAK-906 and an intravenous radioactive microtracer. Period 2 addresses mass balance after an oral radioactive solution, with urine and feces named in the study purpose. The registry’s secondary outcomes span concentration peaks, total exposure, terminal disposition, clearance, distribution, and radioactivity. Together, these measures represent different parts of a drug-disposition profile rather than a single clinical outcome.

The record is also a useful reminder that a clearly defined endpoint is not the same as a reported result. The primary measure and its confidence-interval form are described, but the numerical estimate and interval are not reported in the registry record. Without them, readers cannot assess the observed magnitude or precision of the bioavailability estimate.

Finally, the single-group, nonrandomized structure limits comparative interpretations. The dosing groups should not be treated as randomized controls, and the safety counts should be read descriptively. Enrollment is reported as 6, but the record does not report the primary analysis count or a sample-size justification. These details constrain what can be concluded from the registry entry.

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 entry does not report the primary absolute bioavailability estimate or its 90% confidence interval. It also does not report numerical results for the listed secondary pharmacokinetic outcomes or the mass-balance assessment. As a result, the central quantitative findings cannot be evaluated from the registry record.

The study is described as single-group, with allocation not applicable and no masking. There is no randomized parallel control group, so the listed dosing groups do not support a like-for-like treatment comparison. The registry safety counts are descriptive and should not be interpreted as comparative estimates.

The study enrolled 6 healthy male participants. The record does not report how many participants contributed to each analysis, the participant flow, or any exclusions from the pharmacokinetic set. Although that set is defined by protocol compliance and evaluable pharmacokinetic profiles, the actual analysis population is not reported in the registry record.

The record does not describe the handling of missing or unevaluable measurements, the statistical model details, multiplicity procedures, or sensitivity analyses. It also does not report a sample-size justification or interim analyses. These omissions leave uncertainty about the analysis process beyond the endpoint definition and the stated analysis-population criteria.

Generalizability is limited by the stated population and study purpose: healthy male participants in a Phase 1 pharmacokinetic and mass-balance study. The registry record does not establish how findings would apply to other populations or clinical settings. It also does not provide the detailed types or timing of the other adverse events reported.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Assess Absolute Bioavailability (ABA) of TAK-906 and to Characterize Mass Balance, Pharmacokinetics (PK), Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male Participants — NCT04454918.
• Registry record last updated 2022-03-07; status last verified 2021-12.
• Results first posted 2022-03-07.
• 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.

18. Record Summary

NCT04454918 is a completed Phase 1, single-group study of TAK-906 in healthy male participants. Enrollment was 6. The study assessed absolute bioavailability using oral TAK-906 and an intravenous [14C]-TAK-906 microtracer in Period 1, then assessed mass balance after oral [14C]-TAK-906 solution in Period 2.

The primary endpoint was percent absolute bioavailability based on a dose-normalized AUC∞ ratio, reported as a geometric least squares mean with a 90% confidence interval. The numerical primary result is not reported in the registry record. The registry lists 40 outcome measures and no analysis entries.

No serious adverse events or deaths are reported for either listed dosing group. Other adverse events are reported for 2 participants in the [14C]-TAK-906 50 mg group and none in the TAK-906 50 mg plus [14C]-TAK-906 100 μg group. The design does not provide a randomized control comparison.