A Study of Absorption, Metabolism, Excretion, and Absolute Bioavailability of Carbon-14-Labelled [14C] Selpercatinib (LY3527723) in Healthy Male Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Absorption, Metabolism, Excretion, and Absolute Bioavailability of Carbon-14-Labelled [14C] Selpercatinib (LY3527723) in Healthy Male Participants (NCT05630287), a non-randomized phase 1 study. The primary outcome is Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Selpercatinib in Plasma (Part 1).

2. Clinical Question

3. Trial Design

This completed Phase 1 study was open-label, non-randomized, and parallel, with two parts. Its stated purpose was to examine selpercatinib pharmacokinetics, metabolism, and routes and extent of elimination, as well as absolute bioavailability, in healthy male participants. The study record lists enrollment as 12. The trial started on 2018-08-01, and primary completion was recorded on 2018-09-24.

Part 1 investigated oral dosing with carbon-14-labelled selpercatinib. Participants received a single oral dose of 165 milligram (mg), containing approximately 40 µCi. The primary endpoint is specifically a Part 1 plasma pharmacokinetic measure. Part 2 used a different sequence: a single oral dose of 160 mg selpercatinib followed by a single intravenous dose of less than 100 µg of carbon-14-labelled selpercatinib, containing approximately 1 µCi. This design supports investigation of the study’s absorption, elimination, and bioavailability objectives, but it does not make the arms randomized treatment alternatives.

The listed primary endpoint population consists of participants who received at least 1 dose of study drug and had evaluable pharmacokinetic data. The record does not give a separate analysis population for each part, describe how participants were assigned to the parts, or provide detailed eligibility criteria beyond identifying the population as healthy male participants. The record describes the study as lasting up to 59 days for Part 1 or 46 days for Part 2, including screening and a 7-day safety follow-up. Further operational details, including any protocol deviations or changes, are not reported in the registry record.

The study is a pharmacokinetic investigation rather than a randomized efficacy comparison. Its design and objectives should therefore be read in terms of drug concentration and disposition measurements, not as evidence from a controlled comparison of clinical outcomes. The record does not report a statistical analysis plan or a rationale for the enrollment target.

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: Participants in Part 1 did not participate in Part 2, nor did participants in Part 2 participate in Part 1. Parts 1 and 2 were independent of each other and did not need to be conducted in sequential order.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of study drug and had evaluable PK data.

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: All enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Selpercatinib in Plasma (Part 1), measured over PK: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose.

The primary endpoint is the area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) for selpercatinib in Part 1. It is expressed in hour*nanogram per milliliter (h*ng/mL). In general, an area under a concentration-time curve summarizes measured drug exposure across a specified time interval. AUClast ends at the last quantifiable concentration, so it describes exposure over the observed and quantifiable portion of the concentration profile rather than necessarily representing exposure over an unlimited period.

Pharmacokinetic exposure measures are used to characterize how drug concentrations change over time after dosing. They provide a structured way to describe the amount of drug measured in plasma across the sampling period. This endpoint is relevant to the stated objective of investigating selpercatinib pharmacokinetics, but by itself it does not establish a clinical benefit, compare effectiveness in patients, or provide a complete account of metabolism and excretion.

The registry specifies a geometric mean as the endpoint summary and a geometric coefficient of variation as its dispersion measure. These summaries are suited to describing positive measurements that may vary multiplicatively: the geometric mean gives a central summary on that scale, while the geometric coefficient of variation describes relative variability. The record lists plasma sampling at predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 hours postdose. The numerical AUClast estimate and its dispersion are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods are best understood as descriptive pharmacokinetic methods rather than methods for estimating a randomized treatment effect. The record identifies AUClast as the primary endpoint and names a geometric mean and geometric coefficient of variation as its summary measures. It does not describe a formal hypothesis test, an adjusted model, or a confidence interval for the primary endpoint. Those details are not reported in the registry record.

In general, the area under a concentration-time curve combines concentration measurements across time into a summary of exposure. For AUClast, the integration stops at the time of the last quantifiable concentration. This endpoint therefore depends on observed concentration data and on which measurements can be quantified. It is distinct from a measure extrapolated beyond the last quantifiable sample. The registry’s sampling schedule identifies planned timepoints from predose through 168 hours postdose; the record does not state the exact calculation procedure, interpolation method, or handling of values below quantification limits.

A geometric mean is a central summary suited to positive data whose variation is naturally considered on a multiplicative scale. Conceptually, it summarizes the typical level after accounting for multiplicative rather than additive variation. The geometric coefficient of variation describes relative spread on that scale. These concepts can be useful when pharmacokinetic measurements are right-skewed or when variability grows in proportion to the measurement level. This is general statistical context; the registry does not report the observed distributions or explain why these summaries were selected for this endpoint.

Dispersion and precision are not interchangeable. A measure of variability describes differences among observations, while precision concerns uncertainty in an estimated summary. In general, a confidence interval expresses a range of values compatible with the data and the method used, under the assumptions of that method. The record does not report a confidence interval for AUClast, so its estimate-level precision cannot be assessed from the registry entry. A geometric coefficient of variation, even if reported, would describe variability and would not on its own provide the same information as a confidence interval.

Pharmacokinetic observations are collected at repeated timepoints after dosing. Their interpretation depends on the concentration-time profile, the sampling schedule, and the analysis rules. More frequent observations can describe changes in the profile in greater detail, but a schedule alone does not show whether the observed data were complete. The record does not state how missing samples, non-quantifiable concentrations, protocol deviations, or incomplete profiles were handled. It also does not report the method used to derive individual AUClast values before summarizing them.

The study’s non-randomized, open-label, parallel structure matters for comparisons. Randomization is a general design method for reducing systematic differences in treatment assignment; it is not reported as part of this study. Here, the registry describes different dosing procedures in the two parts and cautions that the arms are not a like-for-like control comparison. Thus, the arm structure should not be treated as if it automatically supports an unbiased randomized contrast. The primary endpoint is expressly a Part 1 measure, and the record does not identify it as a between-arm comparison.

Part 2’s oral and intravenous dosing procedures relate to the stated absolute-bioavailability objective. In general, bioavailability concerns the extent to which a dose reaches systemic circulation, and comparisons of administration routes can inform that question when analyzed using an appropriate pharmacokinetic framework. The registry record does not give the calculation formula, the outcome estimates, or the statistical uncertainty for absolute bioavailability. It is therefore possible to describe the intended design feature, but not to reconstruct the study’s estimate from the information in the record.

The registry lists 32 outcome measures and 0 analyses. This count does not itself establish that all outcomes were analyzed or that any particular multiplicity adjustment was used. The record does not describe a prespecified hierarchy among outcomes, an adjustment for multiple testing, or an interim analysis. Likewise, the enrollment listing and the observed safety counts do not provide a sample-size justification or an observed-power calculation. In general, planning calculations based on an assumed effect are design illustrations, not observed power and not evidence of the probability that a result is true.

For interpretation, the key statistical distinction is between a clearly defined endpoint and a reported estimate. The endpoint definition identifies what was intended to be summarized; it does not give the actual summary, its uncertainty, or the underlying data. Since the registry does not report those results, conclusions should remain limited to the study design, measurement plan, endpoint definition, and stated safety counts.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 32 outcome measures, but the record does not describe how the outcomes were organized for confirmatory or exploratory interpretation. It does not report a hierarchy of endpoints, a multiplicity adjustment, or a prespecified rule for interpreting multiple statistical tests. The record also lists 0 analyses. This means that the registry entry does not supply analysis results or a documented testing strategy from which multiplicity handling could be assessed.

In general, testing or estimating many outcomes can increase the chance of finding an apparently notable result by chance if results are interpreted without considering the number of analyses. Statistical approaches to multiplicity can control or describe that issue, but the appropriate approach depends on the study objectives and analysis plan. No such approach is reported in the registry record, so it should not be assumed that an adjustment was or was not made outside the information recorded.

Missing-data handling is also not reported in the registry record. The primary population is defined as participants who received at least 1 dose and had evaluable pharmacokinetic data, but the record does not state how many participants met that definition, how evaluability was determined, or how incomplete profiles and non-quantifiable samples were treated. The distinction matters because a population definition does not by itself explain how missing observations affect endpoint calculation or the resulting summary.

The record does not report an intention-to-treat population or other analysis populations beyond the stated primary endpoint population. It also does not describe sensitivity analyses for missing data, protocol deviations, or alternative endpoint calculations. These omissions limit assessment of robustness and the extent to which the endpoint estimate would depend on analysis choices. A sample-size justification and any interim analysis plan are not reported in the registry record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse event figures separately for the two arms. In the carbon-14-labelled selpercatinib arm, 0 of 6 participants at risk were recorded as affected by a serious adverse event. In the selpercatinib and carbon-14-labelled selpercatinib arm, 0 of 6 participants at risk were recorded as affected by a serious adverse event. The record lists 0 deaths in each arm.

For other adverse events, 4 of 6 participants at risk were recorded as affected in the carbon-14-labelled selpercatinib arm, and 1 of 6 in the selpercatinib and carbon-14-labelled selpercatinib arm. These are participant counts, not necessarily counts of individual events. The record does not provide event descriptions for the serious events, since no top serious terms are listed, nor does it provide detail about the types or timing of other events.

These figures are descriptive. The arms had different dosing procedures, and the registry identifies the trial as non-randomized rather than a like-for-like control comparison. The counts do not establish a causal difference between the arms or characterize risk beyond the study record. The registry does not report an inferential safety analysis, confidence intervals, or additional context about duration of observation beyond the stated safety follow-up.

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

The registry record describes a study designed to characterize selpercatinib pharmacokinetics and to investigate metabolism, excretion, and absolute bioavailability in healthy male participants. It defines a Part 1 primary endpoint based on plasma AUClast and gives the timing of planned pharmacokinetic sampling. It also describes separate dosing procedures for Part 1 and Part 2. These details explain what the study set out to measure, but they are not a substitute for the numerical results.

The posted record does not report the primary AUClast estimate, its geometric coefficient of variation, a confidence interval, or an inferential analysis. It also does not report a numerical absolute-bioavailability result or detailed metabolism and excretion findings. Therefore, the record cannot support a quantitative statement about the size of these pharmacokinetic measures or the precision with which they were estimated.

The reported safety counts show no participants recorded as affected by serious adverse events in either arm, and no deaths in either arm. Other adverse events were recorded in both arms. Such counts are useful descriptive information, but they do not establish comparative safety because the study was non-randomized and the arms followed different dosing procedures. The registry does not provide event-level descriptions or an adjusted safety comparison.

These results should not be generalized from the registry entry to patients or to clinical outcomes. The enrolled population is described as healthy male participants, and the study’s main focus is pharmacokinetic characterization. It was not a randomized efficacy trial, and the record does not report clinical benefit outcomes. The primary exposure endpoint alone would not determine whether a treatment is effective or appropriate for any individual.

The defensible interpretation is therefore bounded: the study’s structure, dosing, sampling plan, endpoint definition, and selected adverse-event counts are reported, while important numerical pharmacokinetic and analysis results are not reported in the registry record. An unreported estimate should not be mistaken for a null finding or for proof of no effect; it is simply unavailable in this record.

13. Why This Trial Matters Statistically

This study illustrates why a registry’s endpoint definition and its endpoint results must be distinguished. AUClast is clearly identified as the primary Part 1 measure, with a stated unit, summary type, dispersion measure, and sampling schedule. Those details make the intended measurement interpretable. However, without the numerical estimate and its uncertainty, the endpoint cannot answer how much exposure was observed or how precisely it was estimated.

The design also shows why study purpose matters when reading arm-level data. Part 1 used a single oral dose of carbon-14-labelled selpercatinib, while Part 2 used an oral selpercatinib dose followed by an intravenous labelled dose. These procedures align with pharmacokinetic and bioavailability objectives, but do not create a randomized comparison of otherwise interchangeable groups. The registry itself cautions that the arms are not a like-for-like control comparison.

Statistically, the record distinguishes several kinds of evidence: a measurement plan, summary specifications, and descriptive safety counts. None should be confused with an inferential treatment comparison. The record lists 32 outcome measures and 0 analyses, but does not explain multiplicity handling, missing-data methods, or a statistical analysis plan. Recognizing what is and is not documented helps prevent readers from treating design details as results.

The study is also a useful example of how pharmacokinetic research differs from clinical outcome research. Concentration-time measurements describe exposure and disposition; by themselves, they do not establish clinical benefit or answer comparative treatment questions. The registry’s limited results record makes that boundary especially important. Sound interpretation depends not only on the endpoint chosen, but also on the reported estimate, uncertainty, analysis population, and study design.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record describes a population of healthy male participants. This limits the population directly represented by the study and does not provide information about other demographic or clinical groups. The record does not give participant-level characteristics, so the range of ages or other baseline features cannot be assessed from this entry.

Enrollment is listed as 12, and the safety reporting lists 6 participants at risk in each arm. The record does not explain the basis for the enrollment target, report a sample-size justification, or show whether every participant contributed evaluable data to the primary endpoint. The endpoint population is defined by receipt of at least 1 dose and evaluable pharmacokinetic data, but the number meeting that definition is not reported in the registry record.

The study was open-label and non-randomized, and the two arms had different dosing procedures. These features mean that arm-level differences should not be interpreted as randomized treatment effects. The primary endpoint applies to Part 1, while Part 2 has a distinct dosing sequence related to the absolute-bioavailability objective. The record does not report a direct comparative analysis between the parts.

Important result and analysis details are absent. Numerical pharmacokinetic estimates, uncertainty measures, bioavailability results, metabolism and excretion results, handling of missing or non-quantifiable samples, and multiplicity methods are not reported in the registry record. The record also does not provide detailed adverse-event terms or an inferential safety analysis. These limitations constrain assessment of precision, robustness, and the completeness of the reported findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Absorption, Metabolism, Excretion, and Absolute Bioavailability of Carbon-14-Labelled [14C] Selpercatinib (LY3527723) in Healthy Male Participants — NCT05630287.
• Registry record last updated 2025-04-23; status last verified 2025-04.
• Results first posted 2025-04-23.
• 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

NCT05630287 is a completed, open-label, non-randomized Phase 1 study in healthy male participants. Its stated objectives were to examine selpercatinib absorption, metabolism, excretion, pharmacokinetics, and absolute bioavailability. The study had two parts with different oral and intravenous dosing procedures. Enrollment is listed as 12; the start date is 2018-08-01, and primary completion was 2018-09-24.

The primary endpoint was Part 1 plasma AUClast, summarized using a geometric mean and geometric coefficient of variation. Numerical results for this endpoint and the other main pharmacokinetic objectives are not reported in the registry record. The safety record reports 0 serious adverse events and 0 deaths in each arm, with other adverse events affecting 4 participants in one arm and 1 in the other. Because the study was non-randomized and the arms were not like-for-like controls, these counts are descriptive rather than a causal comparison.