Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-MD1003 in Healthy Male Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-MD1003 in Healthy Male Subjects (NCT04223232), a na phase 1 study. The primary outcome is Mass Balance Recovery of Total Radioactivity: CumAe (Urine).

2. Clinical Question

The study also planned pharmacokinetic assessments involving MD1003, bisnorbiotin, biotin sulfoxide, and total radioactivity. Listed measures include timing and magnitude of plasma concentrations, areas under concentration curves, and the terminal elimination parameter lambda-z. These measures describe different aspects of concentration over time; they do not create a controlled comparison. With a single group and no comparator, the main statistical task is descriptive characterization of recovery and concentrations after the dose. The registry record does not establish whether the observed urinary recovery captures all routes of elimination, and the primary endpoint alone should not be treated as a complete account of whole-body mass balance.

3. Trial Design

This is a completed Phase I study with a single-group, nonrandomized, open-label design. The registry lists an enrollment of 6 and describes a single-center investigation in healthy male subjects. The intervention is a single oral dose of 100mg of [14C]-MD1003. The study title and summary identify its focus as mass balance recovery, metabolite profiling, and metabolite identification after dosing. Radioactivity was to be followed in blood, urine, and faeces.

Because there is one group, there is no randomized treatment allocation and no like-for-like control arm. The design is suited to collecting descriptive information after administration, including the amount of radioactivity recovered through specified routes and the time course of measured plasma concentrations. An open-label design means the study is not masked; the registry lists masking as none. The record does not report a blinding procedure, and none should be inferred.

The primary endpoint is cumulative urinary total-radioactivity recovery, summarized as a mean and standard deviation. Measurements are described from pre-dose through 312 hours post-dose, with collection times at 0/12/24/48/72/96/120/144/168/192/216/240/264/288/312 hours. Secondary outcomes include Tlag, Tmax, Cmax, AUC measures, the percentage of AUC extrapolated beyond the last measurable concentration, and lambda-z for specified analytes. The record lists 26 outcome measures and 0 analyses.

The study start and primary completion dates are recorded as 2019-12-10 and 2020-01-22, respectively. It is marked completed. The registry record does not report the rationale for the enrollment size, eligibility criteria beyond the healthy male population description, the handling of incomplete collections, or a detailed statistical analysis plan. Its sample-size illustrations are planning exercises based on a two-arm equal-allocation assumption, whereas the actual trial is single-group; those illustrations are not a description of observed allocation or observed power.

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

Reasons for not completing this period:

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 Mass Balance Recovery of Total Radioactivity: CumAe (Urine), measured over Pre-dose to 312 hours post-dose.

The primary endpoint is cumulative amount of total radioactivity excreted in urine, expressed in mg equiv. The registry specifies a mean as the summary measure, with standard deviation as the measure of dispersion, over the period from pre-dose to 312 hours post-dose. Urine measurements are listed at 0/12/24/48/72/96/120/144/168/192/216/240/264/288/312 hours.

Mass-balance studies track radiolabeled material to describe recovery after administration. A radiolabel allows measurement of total radioactivity, which can include the administered compound and radioactive material associated with its metabolites. Urinary recovery is therefore useful for describing one route by which radioactivity leaves the body over the observation period. It does not, by itself, identify every chemical species contributing to the measured radioactivity or describe recovery in other routes. The registry also notes that radioactivity was followed in blood and faeces, but the primary endpoint is specifically urinary cumulative recovery.

The mean describes the central level of recovery across participants, while the standard deviation describes how dispersed participant values are around that mean. These summaries answer different questions: a mean alone would not show how similar or variable individual recoveries were. The primary endpoint’s numerical mean and standard deviation, and any participant-level values, are not reported in the registry record. Consequently, the definition and intended role of the endpoint can be described, but the amount recovered and its observed variability cannot be interpreted from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation begins with the design. This trial has a single group, no random allocation, no masking, and no separate comparator. Its main role is descriptive: to characterize measurements after a single dose. In a comparative trial, an effect estimate may be expressed as a contrast between groups. Here, there is no such randomized contrast. The primary endpoint is instead a participant-level quantity summarized across the enrolled group by a mean and standard deviation.

What does a mean describe?

For a continuous outcome such as cumulative radioactivity in urine, the mean gives the arithmetic average across the observations included in the analysis. It provides a compact summary of the group’s central level. It does not show the full distribution, reveal whether values are clustered or widely spread, or describe the time pattern unless separate time-specific results are given. In this registry record, the primary endpoint’s mean is not reported, so its level cannot be interpreted.

What does the standard deviation add?

The standard deviation describes the spread of participant values around the mean. A small standard deviation relative to the mean can indicate less between-participant variation in the measured outcome; a larger one can indicate more variation. Such interpretation depends on the scale and distribution of the measurement. The registry identifies standard deviation as the dispersion measure, but its numerical value is not reported. Thus, variability cannot be characterized from the endpoint definition alone.

How is cumulative recovery interpreted?

A cumulative amount sums recovery up to a specified collection time. The listed schedule proceeds from pre-dose through 312 hours post-dose. In general, serial cumulative measurements can show how recorded recovery builds over the observation period. That description depends on observed values at each time; the schedule by itself does not establish the shape or completeness of a recovery curve. The primary endpoint is urine-specific. Although the study summary says radioactivity was followed in blood, urine, and faeces, the primary outcome does not combine those routes into a single reported mass-balance result.

What do the pharmacokinetic summaries represent?

The secondary outcomes list several kinds of plasma measures. Tlag is the time before the first measurable concentration, Tmax is the time of maximum plasma concentration, and Cmax is that maximum concentration. AUC is an integral-like summary of concentration over a stated interval and represents exposure over time. The record distinguishes AUC from time zero to the last measurable concentration from AUC extrapolated to infinity for MD1003 and total radioactivity. It also lists the percentage of AUC extrapolated beyond the last measurable concentration, and AUC from 0 to 12 for the listed analytes. Lambda-z is a parameter describing the terminal portion of a concentration-time profile. These measures are not interchangeable: some describe timing, some a peak, and some accumulated exposure. Their actual estimates are not reported in the registry record.

What do uncertainty summaries tell readers?

In general, an interval estimate such as a confidence interval communicates uncertainty around an estimated quantity, subject to the model and sampling assumptions used. It is not the range containing every individual observation. A standard deviation instead describes observed spread in the data. Neither can be inferred merely from the number enrolled. The record does not provide a confidence interval for the primary endpoint, and the mean and standard deviation are also not reported. There is therefore no basis for describing the precision of the observed urinary recovery.

How should the planning illustrations be understood?

The record describes sample-size calculations as planning illustrations based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is framed as a stated fraction of the observed effect. These are planning assumptions, not a feature of this study’s actual design: the trial has a single group rather than two equally allocated arms. Such calculations do not provide observed power, do not establish that the trial was adequately powered for its descriptive purpose, and do not replace outcome estimates. The record does not report the protocol’s sample-size justification.

What cannot be assessed from the listed methods?

The registry record lists 26 outcome measures and 0 analyses. It does not report a detailed analysis plan, an inferential model, a method for handling values below assay limits, or an approach to missing observations. Those choices can matter for pharmacokinetic summaries and cumulative recovery. The record also does not state whether any interim analysis occurred. No such method or procedure should be inferred from the fact that outcomes and a schedule are listed.

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("MD1003")
n   <- c(6)
m   <- c(70.9)
sp  <- c(16.9)
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  MD1003  6  70.900  16.900  53.165  88.635

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 26 outcome measures, including the primary urinary-recovery endpoint and secondary pharmacokinetic summaries for MD1003, bisnorbiotin, biotin sulfoxide, and total radioactivity. Looking at many outcomes creates a multiplicity issue when researchers make multiple statistical tests: the chance of at least one apparently unusual result can increase as the number of tests grows. In general, a prespecified primary endpoint helps distinguish the main study question from secondary descriptive questions. The registry identifies a primary endpoint, but does not report an adjustment method for multiple testing or a detailed hierarchy for interpreting secondary outcomes. It lists 0 analyses, so inferential tests and their multiplicity handling are not reported.

The registry record does not report how missing urine collections, incomplete time points, or other missing measurements were handled. In general, missingness can affect cumulative recovery if unobserved collections contribute to the total, and missing concentration observations can affect pharmacokinetic summaries. The impact depends on when and why data are missing and on the analysis method; neither the pattern nor method is reported.

The analysis population is also not described beyond the enrolled group of 6 healthy male subjects. The record does not state how many participants contributed to the primary endpoint or whether any participants were excluded from particular outcome analyses. It does not report a per-protocol or other analysis-population definition. Consequently, the listed enrollment should not automatically be taken as the denominator for every outcome. These omissions limit assessment of selection, completeness, and reproducibility of the reported analyses.

12. 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 6 participants at risk for serious adverse events and 0 affected by serious adverse events. It also reports 6 at risk for other adverse events and 2 affected. Deaths are reported as 0. The record does not list any top serious adverse-event terms. These counts describe the adverse-event fields recorded for this study; they are not estimates from a comparison with an untreated group.

In general, a count of participants affected is different from a count of event episodes: one participant can potentially experience more than one event, and a participant count alone does not describe event duration, intensity, or causal attribution. The record’s figures do not identify the terms for the 2 other adverse events, their severity, timing, or relationship to study treatment. The absence of listed serious-event terms does not provide details about all events, and the zero serious-event count should be read alongside the small group size and the study’s descriptive purpose.

These figures summarize recorded events in a small group of healthy male subjects after a single dose. They do not support a comparative safety estimate, since there is no control arm. The registry record does not report additional detail needed to characterize the events or assess how completely they were collected.

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

The study addresses a pharmacokinetic and mass-balance question: what urinary recovery and related concentration measures are observed after a single oral dose of radiolabeled MD1003 in healthy male subjects? Its single-group design and tracking of radioactivity in blood, urine, and faeces are aligned with descriptive characterization rather than a randomized comparison. The primary endpoint is clearly specified as cumulative urinary total-radioactivity recovery, with a mean and standard deviation over a stated collection period.

What the registry record does not establish is the observed amount recovered. The primary mean and standard deviation are not reported, nor are numerical results for the listed secondary outcomes. Therefore, the record does not allow readers to quantify urinary recovery, characterize its observed variability, or assess the listed concentration measures. The completed status is not itself a finding.

The design also does not answer whether MD1003 is more effective than another treatment or whether it changes a clinical outcome. No comparator is included, and the listed population consists of healthy male subjects. The study’s focus is recovery, metabolism, and pharmacokinetic description, not a treatment-effect comparison in a patient population.

In general, the value of a mass-balance study is that the radiolabel can help track total radioactivity through sampled routes and inform characterization of compounds and metabolites. But urinary recovery alone is not equivalent to total recovery across all routes, and radioactivity does not by itself identify the chemical identity of every measured component. The registry describes measurement in other biological materials and metabolite profiling, but does not report the numerical findings needed to draw conclusions about those processes.

The record supports a precise description of study structure, population, dose, endpoint, and planned measurement schedule. It does not support claims about the magnitude of recovery, the completeness of mass balance, the extent of metabolism, or comparative benefit and risk. Those questions require outcome details not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a well-defined measurement plan and an interpretable numerical result. The registry identifies the primary endpoint, units, summary measure, dispersion measure, and collection schedule. These details make clear what investigators intended to quantify: cumulative urinary excretion of total radioactivity after a single dose. Yet the primary numerical mean and standard deviation are not reported in the registry record. A carefully specified endpoint cannot substitute for its observed values.

It also demonstrates why the design must shape the statistical question. A single-group, nonrandomized study has no concurrent comparator. Its summaries can describe what was recorded in participants after dosing, but they cannot by themselves estimate a randomized treatment contrast. That distinction remains important even when the study includes several pharmacokinetic outcomes and a defined dosing procedure.

The small enrollment of 6 makes transparency about individual data, missing collections, and analysis populations especially useful for interpreting descriptive summaries. The registry record does not report those details. In general, small descriptive studies can provide focused information about measurement and biological disposition, but the degree of uncertainty and applicability depends on results and methods that are not available in this record.

Finally, the record’s planning illustrations assume equal allocation between two arms, while the registered trial is single-group. Recognizing this mismatch prevents planning calculations from being misread as a description of the actual study. Nor should such calculations be presented as observed power. Statistically, the key lesson is to keep the endpoint, design, analysis, and interpretation aligned: here, the record defines a descriptive mass-balance question, but does not report the numerical outcomes needed to answer it.

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 primary limitation for interpreting the posted information is that numerical outcome results are not reported in the registry record. The primary endpoint’s mean and standard deviation are absent, as are numerical results for the listed secondary outcomes. This prevents assessment of the observed amount of urinary recovery, variability among participants, or precision of the estimates.

The trial itself enrolled 6 healthy male subjects and used a single-group, open-label, nonrandomized design. With no comparator, the study cannot provide a controlled contrast. The population description also limits the scope of direct interpretation: findings from healthy men would not automatically represent other populations. The registry does not report further eligibility details, so the degree of participant selection cannot be assessed.

The endpoint concerns urinary recovery, while the study summary also describes tracking radioactivity in blood and faeces. The primary endpoint alone does not establish total recovery across routes. The registry record does not provide the numerical results needed to evaluate overall mass balance, and it does not provide metabolite-identification findings in the registry record recorded for this analysis.

Further limitations arise from unreported analysis details. The record does not describe how incomplete collections or missing measurements were handled, which analysis population was used for each outcome, or whether any measurements were excluded. It does not report a detailed statistical analysis plan or the treatment of multiplicity across 26 outcome measures. The record lists 0 analyses, so no inferential methods or statistical comparisons are available for evaluation.

Finally, the sample-size illustrations use two-arm equal allocation assumptions despite the actual single-group design. They should not be treated as evidence of the trial’s design rationale or observed power. The protocol’s sample-size justification and any interim-analysis plan are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-MD1003 in Healthy Male Subjects — NCT04223232.
• Registry record last updated 2020-11-02; status last verified 2020-10.
• Results first posted 2020-11-02.
• 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 NCT04223232 as a completed Phase I study of radiolabeled [14C]-MD1003. It was open-label, nonrandomized, single-group, and conducted at a single center in 6 healthy male subjects. The intervention was a single oral dose of 100mg.

The primary endpoint was cumulative urinary excretion of total radioactivity, measured from pre-dose through 312 hours post-dose and summarized by a mean and standard deviation. The study also listed plasma pharmacokinetic outcomes for MD1003, bisnorbiotin, biotin sulfoxide, and total radioactivity. The registry lists 26 outcome measures and 0 analyses.

Serious adverse events affected 0 of 6 participants at risk; other adverse events affected 2 of 6, and deaths were 0. Numerical primary and secondary outcome results, detailed analysis methods, and missing-data procedures are not reported in the registry record.