Relative Bioavailability Study of Emodepside IR-tablets and Solution: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Relative Bioavailability Study of Emodepside IR-tablets and Solution (NCT03383523), a randomized phase 1 study. The primary outcome is PK (AUC0-7d) of Two New Tablet Formulations of Emodepside in Comparison to the Liquid Formulation (LSF) Oral Solution..

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, open-label, parallel-group study. The registry reports enrollment of 77 and describes the trial as investigating pharmacokinetics, including a food effect, as well as safety and tolerability after single doses of new immediate-release tablet formulations of emodepside compared with oral solution. The study took place from 2017-10-26 to primary completion on 2018-03-26, and its status is completed.

Part 1a included three fasted treatments: 5 mg oral solution, 5 mg of tablet formulation #406, and 5 mg of tablet formulation #416. Part 1b included the two tablet formulations administered fed, each at 5 mg. Part 2 described fasted administration of two 5 mg tablets of formulation #406 or #416. The registry notes that Part 2 treatments might be tested or not, depending on Part 1 results. The posted primary-endpoint results list values for all seven treatment groups.

In a parallel-group design, participants are assigned to treatment groups rather than receiving a sequence of treatments within a crossover design. Randomization describes how assignment was conducted, but the registry record does not report the allocation procedure or any details about stratification. Open-label means masking was not used, consistent with the registry’s masking field. The record does not explain whether the open-label design affected any particular measurement or assessment.

The posted arm sizes range from 10.0 to 12.0 participants. The registry’s overall enrollment figure and the arm-level counts are separate record fields; the record does not provide additional detail about analysis populations or the relationship between enrollment and the endpoint-specific 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: screening details: to check they were healthy and eligible for the study, volunteers had a full examination at screening including physical and neurological examination, vital signs, 12-lead ECG monitoring, safety blood tests (hematology, biochemistry, coagulation and urinalysis), drug screen, alcohol breath test and serology

Only the first 6 of 7 groups are shown.

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.

Population: Healthy Caucasian males subjects

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as PK (AUC0-7d) of Two New Tablet Formulations of Emodepside in Comparison to the Liquid Formulation (LSF) Oral Solution., measured over means from zero to 7 days.

The primary endpoint is the geometric mean of AUC from time zero to 7 days (AUC0-7d), measured in h.ng/ml. AUC is the area under the plasma concentration-time curve; in general, it summarizes drug exposure over a specified period. Here the stated interval begins before dosing and extends to 7 days after dosing. The registry says plasma concentrations were collected at pre-dose and at the listed post-dose sampling times through 168h.

A geometric mean is used for measurements that are naturally interpreted on a multiplicative scale and may be skewed. In general, it summarizes the central level of positive measurements using logarithmic transformation and back-transformation. It is not the same as an arithmetic average. The registry also reports geometric coefficient of variation as the dispersion measure, which describes variability around the geometric mean on a relative scale.

Pharmacokinetic exposure measures are useful in formulation studies because they describe how much drug is present in plasma over time. AUC is one aspect of exposure; it does not by itself describe every feature of the concentration-time profile. The stated endpoint is not a clinical disease outcome, and the posted record does not report a link between these pharmacokinetic values and clinical benefit.

The endpoint title refers to comparison of the two tablet formulations with the oral solution, but the results are presented as separate treatment-group estimates. No inferential comparison estimate or confidence interval is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It identifies a randomized, open-label, parallel-group design and reports arm-level geometric means and geometric coefficients of variation for AUC0-7d. It does not report a detailed statistical analysis plan, a model for comparing treatment groups, confidence intervals, p-values, or analysis populations. The following explanations of statistical concepts are general; they do not describe methods confirmed for this trial unless explicitly stated.

What does the geometric mean represent?

In general, a geometric mean is calculated by transforming positive observations to a logarithmic scale, averaging those transformed values, and converting the result back to the original scale. This approach is often used for pharmacokinetic measurements because exposure values can be skewed and because ratios between values may be scientifically meaningful. The resulting summary is not interchangeable with an arithmetic mean. The registry identifies the endpoint summary as a geometric mean but does not state how individual measurements were handled before the group summary was calculated.

What does the geometric coefficient of variation describe?

In general, a coefficient of variation expresses dispersion relative to a central value rather than in the original measurement units. A geometric coefficient of variation is suited to summaries based on a log scale. Larger values indicate greater relative spread; they do not describe the uncertainty of the estimated mean in the same way as a confidence interval. The record provides geometric coefficients of variation for each arm, but it does not report confidence intervals for either the means or the dispersion estimates.

Why are confidence intervals important?

In general, a confidence interval communicates the precision of an estimate by giving a range of values compatible with the data under the specified method. For a treatment comparison, an interval around the contrast can show the precision of the estimated difference or ratio. A group mean and a measure of within-group variability do not, on their own, supply that interval. The registry record does not report confidence intervals for the primary endpoint or for any formulation, food-condition, or dose contrast.

Why does the contrast matter?

A comparison question needs a clearly defined contrast: for example, a specified tablet formulation versus the oral solution under a stated feeding condition. The posted results give group summaries, but no contrast estimate or inferential test is reported. Consequently, the descriptive values do not quantify the size or precision of a difference between formulations. The record’s endpoint title states a comparison objective, but the posted results do not provide the corresponding inferential result.

In general, randomization can support fair comparisons by reducing systematic differences between assigned groups, but it does not eliminate chance imbalance, measurement limitations, or uncertainty. An open-label design means masking was not used. For pharmacokinetic measurements, the registry record does not indicate whether this influenced sample collection, laboratory assessment, or analysis. No assumption about those procedures can be made from the posted information.

How should the planning illustration be understood?

The registry describes a sample-size planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. The stated target effect is a fraction of the observed effect. In general, such an illustration explores how many participants per arm might be needed under the chosen assumptions; it is not evidence about the trial’s observed power. The record does not report a sample-size justification used to design this trial, and the planning illustration should not be interpreted as the trial’s prespecified design calculation.

In general, assumptions about effect size, variability, allocation, and the statistical test all affect a planning calculation. A planning exercise based on an observed effect is especially dependent on that estimate, which can be uncertain. No additional assumptions should be inferred beyond those stated in the record. The registry record does not report interim analyses, a detailed model, or a prespecified multiplicity procedure.

10. Multiplicity, Missing Data and Analysis Populations

The study includes several treatment groups, a primary pharmacokinetic endpoint, and secondary safety and tolerability outcomes. The record lists six secondary outcomes, covering treatment-related adverse events, physical and neurological examination findings, vital signs, 12-lead ECG findings, and clinical laboratory test findings. It does not report a multiplicity strategy for handling the several outcomes or possible treatment comparisons. The registry record therefore does not indicate whether any adjustment was planned or how confirmatory claims would be controlled across analyses.

The record reports no posted analyses and does not provide p-values or confidence intervals for the primary endpoint comparisons. Without a stated analysis plan and inferential results, the role of any tests, adjustment procedures, or hierarchy among endpoints cannot be determined. No such procedure should be assumed from the design description alone.

Missing-data methods and analysis populations are not reported in the registry record. It does not state how missing pharmacokinetic samples, incomplete profiles, or participants who did not contribute endpoint data were handled. The reported arm sizes do not establish which participants were included in each analysis or whether all randomized participants were analyzed. The record also does not specify a per-protocol, intention-to-treat, or pharmacokinetic analysis population.

These omissions matter because the approach to incomplete measurements and the choice of analysis population can affect estimated group summaries and comparisons. They also limit assessment of whether the posted estimates reflect all assigned participants or a subset with usable measurements.

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 zero serious adverse events in each listed treatment group and zero deaths in each group. These are the serious-event and death counts in the posted safety data; they do not establish that no other safety findings occurred. The record also gives counts in an other adverse-event category: 3, 5, 2, 1, 5, 0, and 4 across the listed treatment groups, in registry order. These counts are reported alongside the corresponding group sizes, which range from 10 to 12 participants.

The record does not provide serious adverse-event terms, and the list of top serious terms is empty. It also does not provide event descriptions, severity, timing, duration, or a detailed account of attribution for the other adverse events. Six secondary outcomes are described as safety and tolerability measures, including examination, vital-sign, ECG, and laboratory findings, but the registry record does not provide results for each of those measures in the registry record.

In general, zero observed serious events in a small treatment group is a descriptive finding, not proof that an event is impossible or that the treatment has no safety risks. These data should be read as event counts within this study’s reported groups, not as a complete characterization of safety.

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

The posted results describe pharmacokinetic exposure summaries after single-dose emodepside administration in the study’s treatment groups. They document group-level AUC0-7d estimates for two immediate-release tablet formulations, the oral solution comparator, fed tablet groups, and Part 2 fasted tablet groups. The associated geometric coefficients of variation provide information about relative variability in those groups.

Those summaries are not equivalent to a formal demonstration that one formulation is comparable to another. The registry record does not report a ratio or difference between groups, confidence intervals, or a statistical test. Without those results, the precision of any contrast cannot be assessed from the posted information. The descriptive estimates alone do not establish equivalence, non-inferiority, or superiority.

The food-effect objective also requires a comparison defined for fed and fasted administration. The record includes fasted and fed tablet groups, but does not report an inferential food-effect estimate. Similarly, the Part 2 groups have a different stated dose from Part 1, and their group summaries should not be read as a formal dose-response analysis.

The endpoint measures plasma exposure over a specified time interval, not disease outcomes. The study title describes healthy male subjects, and the posted results do not establish clinical effectiveness in people with filariasis or in any other patient population. Safety findings are also limited: the registry reports no serious adverse events in the listed groups, but the available event counts and missing detail do not amount to a complete safety profile.

In short, the record offers descriptive pharmacokinetic and safety observations from this study. It does not provide the inferential comparisons needed to quantify how reliably the formulations differ or to make broader clinical claims.

13. Why This Trial Matters Statistically

This trial is statistically notable because it addresses formulation and food-condition questions using several parallel treatment groups, while its posted primary-endpoint results are arm-level summaries rather than formal contrasts. That distinction is important: separate group means can describe the observed data, but comparison questions are answered most directly by an estimated contrast and its uncertainty.

The endpoint uses a geometric mean and geometric coefficient of variation, statistical summaries commonly suited to pharmacokinetic data. Readers need to distinguish the central exposure estimate from its variability and from the precision of an estimated treatment comparison. The registry reports the first two by group but does not report confidence intervals or inferential contrasts, leaving the precision of the comparison questions unresolved in the posted record.

The design also places several scientific questions side by side: tablet formulation versus oral solution, fed versus fasted tablet administration, and Part 2 treatments at a different stated dose. These are not interchangeable comparisons. Each requires its own defined contrast and relevant analysis. The registry provides treatment-specific summaries, but not results that quantify each contrast.

Finally, the record illustrates why the existence of a planning illustration should not be confused with observed power or with the original basis for trial size. The stated illustration uses assumptions and an observed effect; it is a hypothetical planning exercise. The design justification and detailed analysis plan are not reported in the registry record.

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 main limitation for interpreting the primary endpoint is that the registry reports group summaries without inferential comparisons. No confidence intervals, p-values, or comparison estimates are reported, so the precision of contrasts between formulations cannot be evaluated. The record also does not describe the statistical model or the methods used to derive the endpoint summaries.

The treatment groups differ by formulation, feeding condition, or stated dose. These features mean that the arm-level results do not all represent the same direct comparison. In particular, the record does not give a formal estimate of the food effect, and no single comparison captures all groups. The Part 2 descriptions state that those treatments might be tested or not depending on Part 1 results; the posted results list those groups, but the record does not explain the decision process or analysis implications.

The registry record does not report missing-data handling, analysis populations, or detailed pharmacokinetic sample completeness. It is therefore not possible to determine from the record whether the posted results include all randomized participants or only participants with usable measurements. It also does not report a multiplicity plan, interim analyses, or a detailed statistical analysis plan.

The study is described as phase 1 and as involving healthy male subjects. Its findings are limited to the population and treatment conditions represented in the registry; the record does not establish applicability to patients with filariasis or other populations. Safety interpretation is also limited by the absence of event terms and detailed descriptions. No serious adverse events are listed, but that observation does not rule out uncommon events or characterize risks beyond the study groups.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Relative Bioavailability Study of Emodepside IR-tablets and Solution — NCT03383523.
• Registry record last updated 2020-03-09; status last verified 2020-02.
• Results first posted 2020-03-09.
• 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

NCT03383523 is a completed phase 1 randomized, open-label, parallel-group study titled “Relative Bioavailability Study of Emodepside IR-tablets and Solution.” It enrolled 77 participants and investigated single doses of two immediate-release emodepside tablet formulations compared with oral solution, including fed and fasted groups. The official title describes healthy male subjects.

The primary endpoint was geometric mean AUC from zero to 7 days, with geometric coefficient of variation as the dispersion measure. The registry posts treatment-group estimates and safety counts, including zero serious adverse events in each listed group. It does not report inferential comparisons, confidence intervals, p-values, a detailed statistical analysis plan, missing-data methods, or analysis populations. The posted results are therefore descriptive and do not quantify the precision of formulation or food-effect contrasts.