Safety, Tolerability and PK of Multiple-ascending Doses of Emodepside: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and PK of Multiple-ascending Doses of Emodepside (NCT03383614), a randomized phase 1 study. The primary outcome is Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events.

2. Clinical Question

3. Trial Design

This was a Phase 1 randomized, parallel-group study of multiple oral doses of emodepside in healthy male subjects. Its official title describes it as single-blind, while the registry masking entry says double. That inconsistency means the masking description is not clear from the record alone. The study was placebo controlled and involved dose escalation, as stated in its official title.

The record describes three cohorts of 8 subjects each. In cohort 1, 6 subjects received 5mg emodepside once daily and 2 received matching placebo. In cohort 2, 6 received 10mg once daily and 2 received placebo. In cohort 3, 6 received 10mg twice daily and 2 received placebo. The registry does not report whether cohort progression depended on review of earlier cohort data, so no such decision process can be inferred.

The study evaluated safety, tolerability, pharmacokinetics and pharmacodynamics after dosing over 10 days. The primary outcome is a participant count for adverse events, monitored from screening to follow-up up to Day 120 ±2 days. Listed secondary outcomes include plasma pharmacokinetic concentration-time data during repeated dosing and measures based on plasma exposure, including AUClast and AUC12. The record lists 49 outcome measures, but gives no outcome analyses.

The enrollment is recorded as 24 and the study status as completed. The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, or details of randomization implementation. The listed study dates are not necessary to interpret the posted adverse-event counts, and the record does not provide a formal comparison of the treatment groups.

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: 24 healthy subjects were randomized and received study drug or matching placebo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Adverse events were determined in the Safety population. Adverse events were monitored from Screening (Day -28 and until Day -3) to Follow-up (up to Day 120 ±2 days). AE=adverse event; OD=once daily; BID=twice daily.

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 Safety and Tolerability of Emodepside After Multiple Doses as Measured by Number of Participants With Adverse Events, measured over up to 120 days.

The primary endpoint is the number of participants with adverse events after multiple doses of emodepside. Its description covers deaths, serious adverse events and treatment-emergent adverse events. The safety population is named as the population for determining adverse events, with monitoring from screening through follow-up up to Day 120 ±2 days.

Counting participants with events is a direct way to describe how many people in each group experienced an event during the defined monitoring period. It is relevant in an early-phase safety study because it organizes safety observations by treatment group and can include events of differing severity. Serious events and other treatment-emergent events should not be treated as interchangeable categories: seriousness describes an event classification, while the broad treatment-emergent category captures events occurring during the specified period.

The registry record reports counts for serious and other adverse events, as well as deaths, by group. It does not report a complete primary-endpoint analysis that combines all the stated categories into one result. It also does not give event-onset timing, duration, severity grading beyond the serious-event category, or a formal comparison for the primary endpoint. The listed follow-up period is part of the endpoint context; it does not by itself establish that every participant completed the same duration of observation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

A participant count records how many people in a group experienced an event meeting the specified definition during the observation period. It is a descriptive measure. It does not, on its own, show how many total events occurred, because one participant may experience more than one event. Nor does it show how long participants were observed or whether follow-up was complete for everyone.

The primary endpoint is expressed as a number of participants and names deaths, serious adverse events and treatment-emergent adverse events. The posted results separate serious and other adverse-event counts by group. Because the record does not give a complete analysis combining all endpoint categories, those results should be described as reported rather than reconstructed into a broader endpoint.

What does a serious adverse event count mean?

Seriousness is an event classification, not a statistical measure of treatment effect. A count of participants with serious events indicates how many participants were recorded in that category. It does not reveal the severity of events that were not classified as serious, how events were assessed for relatedness, or whether a participant had more than one event. Those details are not reported in the registry record.

The listed serious-event terms and percentages add descriptive detail, but they do not substitute for group-specific analyses. In particular, a percentage without a clearly stated group and denominator cannot support a direct comparison between emodepside and placebo. The record lists anal fistula and anal abscess at 16.7% each, but the information does not state the treatment group for each term.

Why does a confidence interval matter?

As a general statistical concept, a confidence interval describes uncertainty around an estimate under a specified method and its assumptions. It helps distinguish the central estimate from the range of values that remain compatible with the data and method. The registry record does not report confidence intervals for the adverse-event results. With only counts posted, readers cannot use an interval from this record to assess the precision of a treatment-group difference.

A formal comparison would also require a defined estimand and analysis method: for example, a clear statement of which outcome categories are compared, the population included, and how incomplete follow-up is handled. The record identifies the safety population but does not provide those inferential details. No p-values or model-based estimates are reported.

What is over-dispersion, in general?

As a general concept, over-dispersion occurs when observed variability in event counts exceeds what a statistical model assumes. It can matter in analyses of recurrent events, where some participants may have many events while others have none. The posted primary outcome is a count of participants with events rather than a reported recurrent-event model, and the registry record gives no over-dispersion assessment. It is therefore not appropriate to claim that such a model was used or needed for this analysis.

What can planning assumptions tell readers?

The registry record states that planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the effect set as a fraction of the observed effect. It also distinguishes between planning quantities expressed as participants per arm and time-to-event quantities expressed as total events. These are planning conventions, not observed outcomes and not evidence about the trial's original design.

The record explicitly describes the illustrations as computed from the observed effect rather than from the trial's own design. They should not be interpreted as observed power. The record does not state that these assumptions guided enrollment, and no sample-size justification is reported. The sponsor's statistical analysis plan and any prospective power calculation are not reported in the registry record.

What can be inferred from the posted counts?

The counts show the recorded distribution of serious and other adverse events across the listed dose cohorts and placebo group. They do not provide a causal estimate of emodepside's effect on safety, a measure of comparative precision, or a basis to generalize beyond the study population and observation period. Randomization is stated in the record, but details of implementation and the statistical analysis are not reported. Interpretation should therefore remain descriptive and tied to the trial as recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 49 outcome measures, including multiple pharmacokinetic outcomes, and reports 0 analyses. It does not describe a multiplicity adjustment, a hierarchy among outcomes, or a prespecified strategy for choosing which results to emphasize. When a study evaluates many outcomes, general statistical practice recognizes that the chance of chance findings can increase if results are tested repeatedly without an appropriate plan. The record does not show whether any such testing or adjustment occurred.

Missing-data methods are not reported in the registry record. The outcome population is identified as the safety population, and the adverse-event monitoring period is described as extending from screening to follow-up up to Day 120 ±2 days. However, the record does not say how participants with incomplete observation, withdrawals, missed assessments or unavailable event information were handled. The reported counts should not be assumed to include an identical observation duration for every participant.

The record does not report a statistical analysis plan, rules for handling intercurrent events, or an analysis population definition beyond the safety-population description. It also does not provide a formal analysis of treatment differences. As a result, the posted outcomes can be interpreted descriptively, but the record does not allow a reader to evaluate prespecified multiplicity control or the influence of missing data on inferential results.

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 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anal fistula (16.7%), anal abscess (16.7%).

The serious adverse-event counts are 1 participant in the 5mg emodepside once-daily group and 0 in the 10mg once-daily group, 0 in the 10mg twice-daily group, and 0 in the placebo group. The recorded death count is 0 in each group. These are participant counts, not counts of all events, and they do not show event duration, outcome, timing or suspected relation to study treatment.

The record also lists other adverse-event counts of 5, 6, 6 and 4 across the three emodepside cohorts and placebo group, respectively. Those counts are descriptive and should not be combined with the serious-event counts to create a total: the record does not say whether participants appear in both categories. Anal fistula and anal abscess are each listed among the serious-event terms at 16.7%, but the record does not identify their group-specific context in the posted details.

Zero recorded serious events or deaths in a group does not establish that the risk is zero. The record reports no confidence intervals or comparative analysis, and the study population and follow-up are limited to those described in the registry.

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

The results answer a limited descriptive question: what serious and other adverse-event counts were recorded for the listed emodepside dose cohorts and placebo group during this Phase 1 study. The registry reports one participant with a serious adverse event in the 5mg once-daily cohort, none in the other listed groups, and no deaths in any group. It also reports other adverse-event counts for each group. These observations can be read as a record of events in the study, not as a definitive estimate of comparative safety.

The data do not establish that emodepside caused or did not cause a particular event. The record gives no formal analysis of event relatedness, no inferential comparison, and no confidence intervals or p-values. The counts alone do not quantify uncertainty or account for possible differences in observation time. They also do not show how the results would apply to people with filariasis or other patient populations, because the participants are described as healthy male subjects.

The trial also included pharmacokinetic and pharmacodynamic objectives, with several secondary pharmacokinetic outcomes listed. However, no analyses are reported in the registry record, so the listed objectives should not be mistaken for reported findings. This record does not provide evidence about long-term outcomes beyond the stated monitoring period, nor does it provide a statistical analysis plan or sample-size justification.

In general, early-phase studies can characterize exposure and collect initial safety observations, but broad conclusions require adequate data and suitable analyses for the question being asked. Here, the appropriate reading is narrow: the counts describe what was recorded in the study groups. They do not prove an absence of risk, establish a treatment effect, or support medical decisions.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between recording outcomes and analyzing them. The registry identifies a primary safety outcome and reports group-level participant counts, but it lists 0 analyses. Without an inferential analysis, readers can describe the counts but cannot assess a quantified treatment difference or its precision.

The randomized, placebo-controlled, parallel-group design provides a structure for comparing dose cohorts with placebo. The design label alone does not supply the result of such a comparison. The registry record does not report how randomization was implemented, whether analyses were planned by dose group, or how multiple outcomes were to be handled. Those omissions make it important not to treat descriptive group differences as established treatment effects.

The record also illustrates why endpoint definitions and outcome categories matter. The primary endpoint description includes deaths, serious adverse events and treatment-emergent adverse events, while the posted counts distinguish serious and other adverse events. Without a reported combined analysis or additional definitions, combining categories could misrepresent the endpoint. Counts of participants also cannot be assumed to represent counts of all events.

Finally, the study has both safety and pharmacokinetic aims, but the registry lists many outcome measures and no analyses. This separates a stated objective from a reported result. For biostatistical interpretation, clarity about the analysis population, observation period, missing data, multiplicity and uncertainty is as important as the raw counts themselves.

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 does not provide inferential analyses for the primary safety endpoint. No treatment-effect estimate, confidence interval or p-value is reported, so the precision of any group comparison cannot be assessed. The adverse-event results are counts and should remain descriptive.

The stated endpoint includes deaths, serious adverse events and treatment-emergent adverse events, but the posted results do not provide a complete analysis of those categories together. The record does not report whether participants could contribute to more than one category, event-level counts, event timing, severity grading beyond seriousness, or relatedness assessments. It also does not explain whether the other-event counts capture all treatment-emergent events as defined for the endpoint.

The monitoring description extends from screening to follow-up up to Day 120 ±2 days, but completeness and duration of observation by participant are not reported. Missing-data handling, withdrawals and incomplete follow-up are not described. The record also lacks a sample-size justification and a statistical analysis plan; the planning illustrations are not described as the original design calculation.

The population is described as healthy male Caucasian subjects, which limits the scope of direct interpretation. The registry title describes the study as single-blind, whereas the masking entry says double, leaving an inconsistency in the recorded design description. Finally, although pharmacokinetics and pharmacodynamics were study objectives and multiple pharmacokinetic outcomes are listed, no analyses are reported for them in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability and PK of Multiple-ascending Doses of Emodepside — NCT03383614.
• Registry record last updated 2020-04-15; status last verified 2020-04.
• Results first posted 2020-04-15.
• 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

NCT03383614 is a completed Phase 1 randomized, placebo-controlled, parallel-group study of oral emodepside in healthy male subjects. The official title describes a single-blind study, while the registry masking entry says double. The record describes three dose cohorts: 5mg once daily, 10mg once daily and 10mg twice daily, each with matching placebo.

The primary outcome concerns the number of participants with adverse events, including deaths, serious adverse events and treatment-emergent adverse events, monitored through follow-up up to Day 120 ±2 days. The registry reports serious and other adverse-event counts by group and no deaths in the listed groups. It lists 49 outcome measures and 0 analyses. No formal treatment comparison, confidence intervals, p-values, statistical analysis plan, missing-data method or sample-size justification is reported in the registry record.