Mass-balance Study of [14C]-APD421 in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mass-balance Study of [14C]-APD421 in Healthy Volunteers (NCT02881840), a na phase 1 study. The primary outcome is Mass Balance.

2. Clinical Question

3. Trial Design

This was a Phase 1, completed, open-label, single-dose, single-period, single-group study. The official title describes an assessment of mass-balance recovery, metabolite profile and identification after intravenous administration of [14C] APD421 to healthy male subjects. The brief summary also identifies pharmacokinetics as an objective. The registry lists Acacia Pharma Ltd as the sponsor.

Enrollment was 6. The study is described as non-randomised, with allocation marked not applicable, masking marked none, and a single-group model. These features mean the record describes an observational sequence after administration rather than a comparison between assigned treatment groups. No control arm or placebo is listed, so the study cannot estimate a treatment difference against a concurrent comparator.

The registry records the start and primary completion as 2016-08 and the status as completed. These administrative dates do not establish how long each participant was followed or whether each participant completed every assessment. Participant flow, withdrawals, and the number contributing to the primary endpoint are not reported in the registry record.

The primary endpoint is mean recovery of radioactivity in excreta, expressed as percent excreted, with a timeframe of 168 hours and full range identified as the dispersion measure. The endpoint description specifies a single intravenous dose of carbon-14-labelled APD421. No protocol details beyond the listed design and objectives, and no statistical analysis plan, are reported in the registry record. In particular, the rationale for the enrollment target is not reported there.

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 Mass Balance, measured over 168 hours.

The primary endpoint is the mean recovery of radioactivity in excreta after a single intravenous dose of carbon-14-labelled APD421. It is expressed as percent excreted and the stated timeframe is 168 hours. Because the administered compound carries a radioactive label, measuring radioactivity in excreta can describe recovery of labelled material, including material associated with the parent compound or its metabolites. The registry’s endpoint description does not provide a breakdown by route of excretion or chemical form.

Mass-balance assessments are used to characterize the disposition and recovery of a labelled compound. In general, recovery over a defined observation period can help describe how much measured radioactivity has been collected in excreta during that period. It does not, by itself, establish the identity of every recovered substance or explain the clinical effects of a drug. Those questions require other measurements and interpretation.

The record identifies the summary measure as a mean and the dispersion as full range. A mean summarizes the group’s central value, while a full range describes the span from the lowest to the highest observed value. Neither the mean nor the range is numerically reported in the registry record. Consequently, the endpoint’s magnitude, participant-to-participant spread, and completeness of recovery cannot be assessed from the posted numerical results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is limited. It describes a single-group study, one primary outcome measure, and a mean with full range as the summary approach. It does not report a statistical analysis plan, a numerical primary endpoint result, or an analysis record. The concepts below explain how these design and summary choices are generally interpreted; they do not describe undocumented procedures from this study.

What does a single-group design estimate?

In general, a single-group study describes observations in participants who receive the study intervention. Here, the listed intervention is [14C]-APD421, and the primary question concerns the recovery of radioactivity in excreta. There is no concurrent group receiving another intervention, so there is no between-group contrast to estimate. The study’s stated design is compatible with a descriptive mass-balance objective, but it does not support a randomized comparison of treatments.

Randomization is generally used to make assigned groups comparable, on average, with respect to measured and unmeasured factors. Because allocation is marked not applicable and there is only one group, randomization-based comparisons do not apply to this record. Open-label status means masking is listed as none. The registry does not say whether laboratory personnel or those assessing outcomes were masked through separate procedures, so no such procedure should be assumed.

What does the mean and full range convey?

A mean is a measure of the group’s central tendency. It can summarize average recovery, but it does not show how individual observations are distributed. The full range describes the lowest and highest observed values and can indicate the span of observations, although it does not reveal how many participants were near either end or how values were distributed between them. In general, a range can be strongly affected by extreme observations, especially in a small group.

The registry identifies these summaries but does not provide their values. Thus, there is no posted mean or range to interpret. A confidence interval, if reported, would convey uncertainty about an estimated quantity under specified assumptions; it would not show the full spread of participant-level values. No confidence interval is reported in the registry record, and one should not be inferred from the listed summary type.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. When that occurs, methods that assume less variability can give uncertainty estimates that are too narrow. This matters when outcomes vary substantially between participants or when the model’s assumptions do not fit the data. The registry does not report a model, a variance estimate, participant-level results, or an assessment of over-dispersion for this endpoint. It is therefore not possible to determine whether the issue arose or how it was handled.

What can the planning illustrations tell us?

The page includes a sample-size section based on planning assumptions, not the study’s own design justification. The stated assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event tables, the stated quantity is the total number of events using the Schoenfeld approach; other tables use participants per arm.

These are hypothetical planning calculations, not observed power and not a reconstruction of the enrolled study’s design. A two-arm planning illustration does not change the fact that this registry record describes a single group with no comparator. The registry does not report a sample-size justification for enrolling 6 participants, and the numerical inputs or outputs for any particular planning illustration should not be treated as findings from this trial.

What remains unavailable?

The number of analyses is listed as 0, and the record contains one outcome measure. No inferential test, model specification, adjusted analysis, confidence interval, or analysis population is described. The primary outcome’s numerical result is also absent. These omissions prevent evaluation of the endpoint’s estimate, its precision, and the assumptions behind any analysis. General statistical principles can explain what such quantities would mean, but cannot recover them from the design description.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and identifies mass balance as the primary endpoint. The number of analyses is listed as 0. The record does not describe a statistical analysis plan, additional prespecified endpoints, an ordering of hypotheses, or an adjustment for multiple testing. It is therefore not possible to determine whether multiplicity was considered elsewhere or whether any adjustment was planned. The absence of reported analyses should not be read as evidence that no analyses were performed; it means that analyses are not reported in the registry record.

Missing-data handling is also not reported in the registry record. The endpoint timeframe is 168 hours, but the record does not state whether all participants contributed samples through that timeframe, how incomplete collections were treated, or whether any observations were excluded. Enrollment of 6 and a completed study status do not establish endpoint completion for each participant. No imputation method, sensitivity analysis, or missingness summary is reported.

The analysis population is not described. The registry does not specify whether the primary endpoint was intended to use all enrolled participants, those who received the intervention, or participants with sufficient collection data. It also does not provide participant disposition or the number contributing to the primary endpoint. As a result, the relationship between enrollment and the analyzed group cannot be assessed.

These omissions matter because interpretation depends not only on the endpoint definition but also on which observations are included and how incomplete data are handled. With no posted numerical endpoint result, the reader cannot judge whether missingness or analysis-population choices materially affected the reported summary.

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 safety figures for the [14C]-APD421 group, with 6 participants at risk for serious adverse events and 0 affected. It reports 6 participants at risk for the category labelled other adverse events and 6 affected. Deaths are listed as 0. These are counts of participants affected in the registry’s categories, not a description of event severity beyond the serious-event classification.

The other-adverse-event figure should not be treated as a count of distinct events, because the record reports participants affected and does not provide event terms or event totals. The registry also does not define the category further in the information. The serious-adverse-event figure does not mean that no adverse events occurred: the separate other-adverse-event category lists participants as affected.

These safety counts come from a group of 6, with no comparator group. They are descriptive and do not establish whether an event was caused by the intervention, how frequently an event might occur in a broader population, or how safety compares with another treatment. The registry does not list serious-event terms, and it does not provide further detail about the other events in this record.

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

This record can establish that a completed, open-label, single-group study enrolled 6 healthy male subjects and assessed a single intravenous dose of carbon-14-labelled APD421. It identifies a primary mass-balance endpoint: mean recovery of radioactivity in excreta, expressed as percent excreted over 168 hours, with full range as the stated dispersion measure. It also records safety counts for the study group.

It cannot establish the numerical amount of radioactivity recovered, the range of participant results, or the precision of the endpoint estimate. Those values are not reported in the registry record. The record also does not provide numerical findings for metabolite profiling, metabolite identification, or pharmacokinetics, despite listing these as study objectives. The endpoint definition alone cannot answer those questions.

This is not a randomized or controlled comparison. The study therefore does not estimate a difference between APD421 and an alternative, and it cannot establish comparative efficacy or safety. The registry lists post-operative nausea and vomiting as a condition, but the study participants are described as healthy male volunteers. The results, even if numerical results were available, would need to be interpreted in the context of that population and the descriptive design.

The safety figures show 0 of 6 participants affected by a serious adverse event, 6 of 6 affected in the category labelled other adverse events, and 0 deaths. These counts should not be used to infer a causal relationship or a rate for a broader population. The category detail and event terms are not reported in the registry record.

In short, the registry provides a clear outline of the study question and design, but not the primary numerical outcome needed to quantify recovery. It supports description of what was intended and of the reported safety counts, not conclusions about the magnitude or precision of mass-balance recovery, comparative effects, or clinical benefit.

13. Why This Trial Matters Statistically

This study illustrates the distinction between a well-defined measurement objective and a reportable numerical result. The registry specifies the measured concept, unit, summary statistic, dispersion measure, and timeframe: mean percent excreted, full range, over 168 hours. Those details help readers understand what the endpoint was intended to represent. However, without the actual mean and range, the endpoint cannot be evaluated quantitatively.

It also shows why study design must be read alongside the endpoint. A single-group mass-balance study can address descriptive questions about recovery after administration. It is not structured to estimate a treatment contrast because there is no comparator. Recognizing that distinction avoids treating a descriptive pharmacology study as if it were a controlled efficacy trial.

The listed sample-size planning assumptions provide another useful statistical lesson. Planning calculations depend on choices such as the target effect, significance level, allocation, and model approximation. Here, those assumptions are explicitly described as planning illustrations rather than the study’s own design, and they do not replace a registry-reported sample-size justification. Nor do they yield observed power or supply missing endpoint results.

Finally, the record demonstrates the importance of completeness in results reporting. Enrollment and completion status alone do not explain participant flow, the analysis population, missing-data handling, uncertainty, or the numerical outcome. The safety counts are informative as descriptive tallies but do not address comparative risk. For statistical readers, the key lesson is to separate a stated study objective, a design that can address that objective, and the results actually available for evaluation.

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 most important limitation of this registry record is that it does not report the numerical result for the primary endpoint. Although the endpoint and summary measure are specified, the mean recovery and full range are absent. This prevents assessment of the amount recovered and the variability among participants. No confidence interval or other measure of uncertainty is reported.

The study enrolled 6 healthy male subjects and had no comparator group. Its findings, even if fully reported, would be descriptive rather than a controlled estimate of a treatment difference. The registry lists post-operative nausea and vomiting as a condition, but the population description is healthy male subjects; the record therefore does not describe a patient treatment comparison for that condition.

Participant flow and endpoint contribution are not reported. The completed status does not show whether all enrolled participants completed collection through the stated 168-hour timeframe. Missing-data procedures and the analysis population are not reported in the registry record, so the reader cannot determine how incomplete or unavailable observations may have been handled.

The record also lacks numerical findings and analysis details for the listed metabolite and pharmacokinetic objectives. It does not report the sample-size justification, a statistical analysis plan, or details of any assessment of model assumptions. The sample-size section’s planning assumptions are not the trial’s own design justification and cannot fill these gaps. Safety information is limited to group counts, without serious-event terms or further detail about the other events. Together, these reporting limits constrain both quantitative interpretation and evaluation of the analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Mass-balance Study of [14C]-APD421 in Healthy Volunteers — NCT02881840.
• Registry record last updated 2019-06-25; status last verified 2019-06.
• Results first posted 2019-06-07.
• 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

This is a completed Phase 1, open-label, single-dose, single-period, single-group study of intravenous [14C]-APD421 in healthy male subjects. Enrollment was 6, and the registry lists Acacia Pharma Ltd as the sponsor. The stated objectives include mass-balance recovery, metabolite profile and identification, and pharmacokinetics.

The primary endpoint is mean recovery of radioactivity in excreta, expressed as percent excreted over 168 hours, with full range specified as the dispersion measure. The numerical endpoint result is not reported in the registry record. The study has no comparator, and the registry reports 0 participants with serious adverse events, 6 affected in the other-adverse-event category, and 0 deaths.

Overall, the record describes the study question and design but does not provide the numerical primary result, analysis population, missing-data approach, or detailed analysis plan.