A Study to Assess Drug-drug Interaction of ZX008 in Healthy Male and Female Study Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess Drug-drug Interaction of ZX008 in Healthy Male and Female Study Participants (NCT06679413), a na phase 1 study. The primary outcome is Maximum Concentration (Cmax) of Midazolam Alone and in Combination With ZX008 at Steady State.

2. Clinical Question

This is a drug-drug interaction question focused on midazolam concentration. The study also assessed the single-dose pharmacokinetics of bupropion and metformin before and after repeat doses of ZX008, according to the brief summary. The primary endpoint named in the record, however, is midazolam maximum concentration. The record does not establish a randomized control group, and the order of treatment is fixed: participants first receive the probe cocktail alone, then ZX008, with the cocktail administered again in the later period. Consequently, the study describes a within-participant sequence rather than a blinded, randomized treatment comparison.

3. Trial Design

The registry identifies this as a Phase 1, single-center, repeat-dose, open-label, fixed-sequence drug-drug interaction study. It is a single-group study with an enrollment of 22 and no randomized allocation. The participants were healthy male and female adults 18 to 55 years of age. The status is listed as completed; the recorded start date is 2024-12-04 and the primary completion date is 2025-06-12.

In Treatment Period 1, participants received the three-probe drug cocktail alone, with the period identified as D1-D5. After a washout period, participants received repeated doses of fenfluramine HCl, identified as ZX008. The adverse-event grouping labels Treatment Period 2 as ZX008 15 mg BID alone on D6-D21, followed by ZX008 15 mg BID plus the probe cocktail from D22-SFU. The primary pharmacokinetic endpoint lists measurements on Day 1 of Treatment Period 1 and Day 22 of Treatment Period 2.

The same participants form the sequence across periods, rather than separate groups assigned to different treatments. That design allows within-participant concentration measurements to be considered across the recorded conditions, but treatment condition and period occur in a set order. The record does not report a randomized or counterbalanced sequence. It also does not report the rationale for the sample size, a protocol-level statistical analysis plan, or whether interim analyses were planned. The arm description is a treatment sequence, not evidence of a parallel control arm.

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: The Participant Flow refers to the Safety Set.

Treatment Period 1: Days 1 - 5

Treatment Period 2: Days 6 - 26

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic set (PKS) consisted of all study participants who received at least 1 dose of any of the study treatments and have at least 1 quantifiable postdose pharmacokinetic (PK) concentration measurement of the probe drugs.

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: Baseline Characteristics refer to the Safety Set which consisted of all study participants who had received at least 1 dose of any of the study treatments.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Concentration (Cmax) of Midazolam Alone and in Combination With ZX008 at Steady State, measured over Day 1 (Treatment Period 1) and Day 22 (Treatment Period 2): Predose, 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10,12, 24, 36, 48, 72, and 96 hours Postdose.

The primary endpoint is the maximum observed plasma concentration, or Cmax, of midazolam alone and in combination with ZX008 at steady state. Cmax records the highest measured plasma concentration after dosing during the specified sampling schedule. The listed unit is nanograms per milliliter (ng/mL), and the registry identifies the summary parameter as a geometric mean with geometric coefficient of variation as the dispersion measure.

For a drug-drug interaction study, comparing exposure under the probe-drug-alone condition with exposure when ZX008 is also administered can help describe whether the observed concentration profile differs between those conditions. Cmax is one measure of concentration and does not, by itself, describe the entire concentration-time profile. The record also lists postdose sampling times through 96 hours for the endpoint, with measurements scheduled on Day 1 and Day 22.

In general, a geometric mean is used for positive concentration measurements when values are better summarized on a multiplicative scale. A geometric coefficient of variation describes relative variability on that scale. These are general statistical interpretations of the specified summaries, not reported findings about this study. The registry record does not report the Cmax estimates, their dispersion values, a treatment contrast, or a confidence interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint summary represent?

The primary endpoint uses Cmax, the maximum observed plasma concentration of midazolam. It is expressed in nanograms per milliliter (ng/mL), and the record specifies a geometric mean and geometric coefficient of variation. In general, Cmax condenses a series of concentration measurements into the highest observed value for a participant under a dosing condition. The sampling schedule matters because the observed maximum depends on when measurements are taken. The listed schedule runs from predose through 96 hours postdose on Day 1 and Day 22.

In general, concentration data are often right-skewed: a smaller number of observations may be relatively high compared with the rest. A geometric mean can be useful for positive, skewed measurements because it summarizes values on a multiplicative scale. A geometric coefficient of variation conveys relative spread on that scale. These general explanations describe the statistical summaries named in the record. The actual values, distributions, and participant-level observations are not reported in the registry record.

How does the fixed sequence affect interpretation?

All participants were assigned to a single treatment sequence rather than randomized to separate arms. The planned sequence compares the probe cocktail alone with the cocktail administered after repeated ZX008 dosing. In general, paired or within-participant analyses use measurements from the same people under different conditions. Such analyses can account for stable participant characteristics that would otherwise contribute to variation between separate groups.

However, a fixed sequence also means the conditions occur in different periods and in a particular order. In general, period effects, changes over time, or residual effects from earlier treatment can complicate interpretation when conditions are not randomized or counterbalanced. The registry record does not report whether these factors were assessed, what washout duration was used, or what model was used to estimate the comparison. The record describes a washout period but does not report its length.

What does a confidence interval contribute?

In general, a confidence interval gives a range of values compatible with the data and the statistical method, reflecting uncertainty in an estimate. A narrow interval indicates greater precision than a wide interval, all else being equal. For a drug-drug interaction analysis, the interval around the treatment contrast would help readers assess the range of plausible differences in the endpoint. The registry record does not report a confidence interval for the primary endpoint, so its precision cannot be evaluated from this record.

A p-value, in general, measures how incompatible the observed data are with a specified null hypothesis under the assumptions of a statistical test. It does not measure the size or clinical importance of an effect, and it does not give the probability that the null hypothesis is true. No primary endpoint p-value or test description is reported in the registry record. The presence of nine analyses in the record does not identify which analyses were confirmatory, which were exploratory, or how their results were tested.

How should the analysis population be understood?

The primary endpoint identifies a pharmacokinetic set. It includes all study participants who received at least one dose of any study treatment and had at least one quantifiable postdose pharmacokinetic concentration measurement of the probe drugs. In general, this definition links inclusion in the analysis to both exposure to study treatment and availability of measurable postdose data. It is not necessarily identical to the enrollment count, because the record does not state how many participants met every criterion for this set.

The registry record does not report the number included in the pharmacokinetic set, how missing or unquantifiable measurements were handled, whether any participants were excluded from the endpoint analysis, or how missing time points affected Cmax calculation. These details can affect which observations contribute to a summary and should be considered when interpreting estimates.

What can planning illustrations tell readers?

In general, sample-size calculations describe the number of participants that might be needed under stated assumptions to detect an effect with a chosen statistical procedure. The record’s planning illustration is described as using 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. These are planning assumptions, not a report of the study’s original design justification. The registry record does not report the protocol’s sample-size justification.

Any sample-size values based on that approach are planning illustrations, not observed power and not evidence that the study had a particular probability of detecting an effect. They depend on the assumed effect and other inputs. The record also distinguishes total-event planning for time-to-event outcomes from participants per arm for other outcomes. The primary endpoint is a pharmacokinetic measure in a single-group fixed sequence, so a two-arm planning illustration should not be mistaken for the actual study design or for the primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures and 9 analyses. Those counts alone do not show which outcomes were primary, which analyses were prespecified, whether tests were confirmatory or exploratory, or whether any adjustment was used to account for multiple statistical comparisons. A multiplicity strategy is not reported in the registry record. Without that information, the role of any individual p-value or interval among multiple analyses cannot be determined.

The primary endpoint is specified as midazolam Cmax, while the study summary also describes pharmacokinetic assessment of bupropion and metformin. The listed secondary outcome is the percentage of participants with treatment-emergent adverse events. The record does not provide the full set of numerical pharmacokinetic results or explain how statistical testing across the endpoints was organized.

The endpoint’s analysis population is defined as participants who received at least one dose and had at least one quantifiable postdose pharmacokinetic concentration measurement of a probe drug. The number meeting this definition is not reported in the registry record. Nor are missing-data procedures reported: the record does not explain how missing samples, unquantifiable concentrations, incomplete profiles, or withdrawals were handled in the endpoint calculations.

The record also does not describe interim analyses, imputation procedures, sensitivity analyses, or the statistical model used for the primary endpoint. These omissions do not establish that such procedures were absent; they mean that they are not reported in the registry record. As a result, readers cannot assess how incomplete data or multiple analyses may have influenced the posted estimates. In any interpretation, the enrollment count should not be assumed to equal the number included in every pharmacokinetic analysis.

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 lists safety findings separately for three treatment-period groups. In the 3-probe Drug Cocktail Alone group (Treatment Period 1: D1-D5), 22 participants were at risk for serious adverse events and 0 were recorded as affected; 22 were at risk for other adverse events and 1 was recorded as affected. In the ZX008 15 mg BID Alone group (Treatment Period 2: D6-D21), the corresponding counts were 22 at risk and 0 affected for serious adverse events, and 22 at risk and 7 affected for other adverse events. In the ZX008 15 mg BID plus 3-probe Drug Cocktail group (Treatment Period 2: D22-SFU), the counts were 22 at risk and 0 affected for serious adverse events, and 22 at risk and 2 affected for other adverse events.

No deaths are recorded in any of the three groups, and the registry lists no serious adverse-event terms. These are period-specific registry counts, not necessarily counts of unique people across the entire study. The record does not report event-level details, duration, severity grades for other events, or attribution to treatment. The counts should therefore be read as the posted safety summaries, not as a complete account of individual events or a causal comparison between treatments.

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

This trial addresses a focused pharmacokinetic question: how midazolam Cmax compares when the probe cocktail is given alone and when it is given after repeated ZX008 dosing. It is a Phase 1 study in healthy participants, with a fixed treatment sequence and repeated dosing. The registry record identifies the endpoint, its summary scale, its sampling schedule, and the population definition for pharmacokinetic analyses.

The record does not report the numerical Cmax results or a treatment contrast. It therefore cannot establish from the posted information whether the measured concentration was higher or lower in either condition, how large any difference was, or how precisely a difference was estimated. The same limitation applies to the numerical pharmacokinetic results for bupropion and metformin described in the study summary. The absence of reported estimates is not evidence that there was no difference.

The record also does not establish a randomized comparison. The same participants received the treatments in a fixed order, so condition and period are linked. In general, this design can make each participant a reference for their own measurements, but it does not provide the protection against period or sequence effects that random allocation can offer. The registry record does not report how those possible influences were evaluated.

The safety entries show no serious adverse events and no deaths in the displayed groups, with other adverse-event counts varying by period. Those findings are limited to the categories and counts reported; they do not describe the full clinical context of every event. The study’s healthy-participant setting and its Phase 1 design also define the scope of the record. Its findings, when reported, would address the specified pharmacokinetic conditions rather than all possible populations or uses.

In short, the posted record describes what the study set out to measure and how it was sequenced. It does not report enough outcome data to quantify the primary comparison or its uncertainty. Interpretation should distinguish the study question and design from results that are not reported in the registry record.

13. Why This Trial Matters Statistically

Drug-drug interaction studies ask whether exposure to a probe drug differs when another treatment is present. This study’s primary endpoint uses midazolam Cmax, a defined concentration summary, and the design measures the same participants under the probe-cocktail-alone and later combination conditions. Those features make the estimand and treatment sequence important: readers need to know both what concentration measure is being compared and the order in which the conditions occurred.

Statistically, the record illustrates why a clear endpoint definition is not a substitute for a reported estimate. Naming Cmax, its unit, geometric mean summary, and dispersion measure gives readers a framework for interpreting results, but it does not reveal the magnitude or precision of the comparison. Estimates and uncertainty are needed to distinguish a small, precisely measured contrast from a larger but imprecise one. Those results are not reported in the registry record.

The study also highlights the difference between a within-participant sequence and a randomized parallel-group design. Repeated measurements in the same individuals can be useful for reducing variability due to stable differences among participants. Yet with a fixed sequence, treatment condition is also associated with study period. The design and analysis therefore need to be understood together, and the registry record does not describe the model or period-effect assessment.

Finally, the separate safety counts demonstrate why adverse-event categories and denominators should be read in their recorded treatment periods. The zero serious-event counts do not describe other events, while the other-event counts do not establish treatment causation. A careful statistical reading keeps these distinct questions separate and avoids drawing conclusions beyond the reported endpoint values, analysis details, and safety summaries.

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 for interpreting the primary endpoint is that numerical Cmax results and a treatment contrast are not reported in the registry record. No confidence interval or p-value for the primary comparison is reported either. This prevents assessment of effect direction, magnitude, and precision. The information also does not give numerical pharmacokinetic results for bupropion or metformin, despite their inclusion in the study purpose.

The study is open-label, single-group, and fixed-sequence, with no randomized allocation. The probe cocktail alone precedes the ZX008-plus-cocktail period, so treatment condition and period are not separated by randomization. The record does not report the analysis model, handling of period or sequence effects, or the duration of the washout period. It describes a washout period without stating its length.

Although enrollment is reported as 22, the number of participants included in the pharmacokinetic set is not reported. The record does not state how missing, incomplete, or unquantifiable concentration measurements were handled, or whether all enrolled participants contributed to the primary analysis. It also does not report a statistical analysis plan, multiplicity adjustment, interim analysis approach, or protocol-level sample-size justification.

Safety information is presented as counts by treatment period. The record does not provide event-level descriptions, severity grades for other events, treatment attribution, or enough detail to establish whether the same participants contributed events in multiple periods. The posted counts should not be treated as a randomized safety comparison. These limitations constrain interpretation of both the pharmacokinetic question and the safety summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Assess Drug-drug Interaction of ZX008 in Healthy Male and Female Study Participants — NCT06679413.
• Registry record last updated 2026-07-02; status last verified 2026-03.
• Results first posted 2026-07-02.
• 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.

18. Record Summary

NCT06679413 is a completed Phase 1, single-center, open-label, fixed-sequence drug-drug interaction study in healthy male and female participants 18 to 55 years of age. Enrollment was 22. Participants received a cocktail of midazolam, bupropion, and metformin alone, followed by repeat doses of fenfluramine HCl (ZX008) and the probe cocktail. The primary endpoint was midazolam Cmax, summarized as a geometric mean with geometric coefficient of variation.

The record reports no serious adverse events and no deaths in the three displayed treatment-period groups. Other adverse-event counts are listed by group. Numerical results for the primary pharmacokinetic endpoint, statistical uncertainty, and the detailed analysis methods are not reported in the registry record. The design and posted safety entries can be described, but the primary treatment contrast cannot be quantified from the reported information.