Pharmacokinetics and Safety of Intravenous Posaconazole (MK-5592) in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-120): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics and Safety of Intravenous Posaconazole (MK-5592) in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-120) (NCT03336502), a na phase 1 study. The primary outcome is Steady State (ss) Average Concentration (Cavg) of Posaconazole of Serial PK (Subgroup 1) on Day 10.

2. Clinical Question

The study asked how posaconazole behaves in blood plasma after intravenous administration in Chinese participants at high risk for invasive fungal infections, and what safety outcomes were recorded during treatment. Its primary pharmacokinetic focus was the steady-state average concentration, or Cavg, among participants in the serial pharmacokinetic sampling subgroup on Day 10. The study description also identifies a target of determining the percentage of participants whose steady-state average plasma concentration reached 500 ng/ml or higher. That percentage is not reported in the registry record.

Because there was no comparator group, this study describes pharmacokinetic and safety observations in participants receiving posaconazole; it does not provide a controlled treatment contrast. The registry lists adverse events, discontinuations due to an adverse event, laboratory and vital-sign changes, survival status, and invasive fungal infection among the secondary outcomes. These listed outcomes do not by themselves establish what was observed for each outcome.

3. Trial Design

The registry identifies NCT03336502 as a completed phase 1 study of intravenous posaconazole in Chinese participants at high risk for invasive fungal infections. It lists enrollment as 70 and describes a single-group model. Allocation is NA and masking is none. There is no randomized control arm or like-for-like comparator in the registry record, so the results are not structured as a between-group efficacy comparison.

The treatment arm was posaconazole. The described schedule was 300 mg by intravenous infusion twice on Day 1, then 300 mg by intravenous infusion once daily on Days 2 to 10 (±1). The arm description also mentions continuation at the investigator’s discretion with intravenous posaconazole or oral suspension, but the continuation details are not fully reported in the registry record. The study description characterizes the participants as neutropenic and undergoing chemotherapy for acute myelogenous leukemia or myelodysplastic syndromes.

Two pharmacokinetic sampling subgroups are described. Subgroup 1 had serial blood draws, including multiple samples on Day 10, to characterize pharmacokinetic parameters. Subgroup 2 had sparse sampling, with a once-daily blood draw for plasma trough determination. The primary endpoint applies to Subgroup 1, and the registry explicitly excludes the sparse-sampling subgroup from that endpoint analysis because its Day 10 sample was intended for trough determination only.

The primary endpoint was a continuous measurement summarized as a mean with standard deviation. The registry lists 14 outcome measures, including safety-related outcomes, but has zero analysis entries. The analysis methods beyond the endpoint description, including the planned statistical model and handling of incomplete observations, are not reported in the registry record. The record’s completed status indicates the study is marked complete; it does not substitute for the unreported endpoint values or analysis details.

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:

Analysis population for the primary outcome, as defined in the registry: Analysis population includes participants who had serial blood draws on Day 10. Sparse PK (subgroup 2) is not included in this analysis because blood was drawn only once on Day 10 for plasma trough determination.

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: Subgroup 1 - Serial PK group, received at least 10 days of POS, and analyzed for plasma trough determination AND PK parameters Subgroup 2 - Sparse PK group, received at least 10 days of POS, and analyzed for plasma trough determination. Both groups received the same dose and drug administration, reflect only different blood sampling schedules.

6. Primary Endpoint

The registry lists the primary outcome as Steady State (ss) Average Concentration (Cavg) of Posaconazole of Serial PK (Subgroup 1) on Day 10, measured over Serial PK (Subgroup 1) on Day 10 at pre-dose, 1 hr. post start of infusion (SOI), end of infusion (EOI), 15 min. after EOI and 4, 8, 12, 24 hours post SOI.

The primary endpoint is the steady-state average concentration, Cavg, of posaconazole in plasma on Day 10 for the serial pharmacokinetic sampling subgroup. Cavg is defined in the registry as AUC0-24hr divided by the dosing interval. It summarizes drug exposure across the dosing interval rather than representing a single blood concentration at one sampling time. The registry describes serial sampling at pre-dose, 1 hr. post start of infusion (SOI), end of infusion (EOI), 15 min. after EOI, and 4, 8, 12, and 24 hours post SOI.

This type of pharmacokinetic measure is used to characterize exposure at steady state. In general, serial samples help describe how concentrations change over time and support calculation of an exposure measure across an interval. A trough measurement from sparse sampling answers a narrower question about concentration at a particular point in the dosing cycle; the registry therefore excludes Subgroup 2 from this Cavg analysis.

The endpoint is reported as a mean with standard deviation, but neither the estimate nor its standard deviation is reported in the registry record. The record also states an objective of determining the percentage with steady-state average concentrations of 500 ng/ml or higher, but does not report that percentage. Consequently, the recorded endpoint definition explains what was intended to be measured, but the available registry information does not show the observed exposure level or its variability.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a continuous pharmacokinetic measure, summarized by a mean and standard deviation. It identifies the population for that outcome as participants with serial blood draws on Day 10. It does not report the endpoint estimate, standard deviation, confidence interval, or a model used to derive the estimate. The explanations below distinguish general statistical principles from methods documented for this study.

What does Cavg represent?

The registry defines Cavg as AUC0-24hr divided by the dosing interval. In general, an area-under-the-concentration curve reflects exposure over time, while dividing by an interval expresses that exposure as an average concentration across the interval. This is different from relying on a single concentration, which reflects only the sampling time. The definition makes the endpoint’s intended interpretation clear, but the registry record does not report the resulting Cavg value.

Why use serial sampling?

In general, repeated samples across a dosing interval help characterize the concentration-time profile. They can support estimation of exposure measures as well as peak, trough, and timing parameters. The study description says Subgroup 1 was sampled serially for Cavg, AUC, Cmin, Cmax, Tmax, total body clearance, and plasma trough determination. It describes Subgroup 2 as having sparse, once-daily sampling for trough determination only. The registry therefore distinguishes the richer sampling schedule used for pharmacokinetic characterization from the narrower sampling purpose in Subgroup 2.

The primary endpoint’s listed Day 10 times include pre-dose, 1 hr. post SOI, EOI, 15 min. after EOI, and 4, 8, 12, and 24 hours post SOI. In general, measurements at different points can reveal changes during and after an infusion. The registry does not report whether every intended sample was collected for every participant, how missing samples were handled, or whether any samples were excluded from the endpoint analysis.

How should a mean and standard deviation be read?

In general, the mean is a measure of central tendency: it summarizes the average observed concentration in the analysis population. The standard deviation describes the spread of observations around that average. A small standard deviation relative to the mean would indicate observations are more closely clustered; a larger one would indicate greater dispersion. This is a general explanation, not a description of the study’s observed dispersion, because neither summary value is reported in the registry record.

A confidence interval, in general, expresses uncertainty around an estimated quantity under the assumptions of the analysis. Its width depends on the observed data and the method used to construct it. The registry record does not report a confidence interval for Cavg, nor does it give a standard error or other precision measure. Therefore, the precision of the estimated average cannot be judged from the record.

What does the study design allow?

The record classifies the design as single-group, with allocation NA and masking none. In general, a single-group pharmacokinetic study can characterize concentration measurements under the regimen studied. It does not, without a concurrent comparator, estimate a between-regimen contrast. A change or event observed during treatment cannot by itself separate treatment effects from other influences. No randomized comparison is described, and the registry’s own note says the arms are not a like-for-like control comparison.

The study lists a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. These are planning assumptions, not a description of the completed single-group design, and any such sample-size values are illustrations rather than observed power. The underlying primary result is not reported in the registry record, so the observed effect and the inputs for such an illustration cannot be assessed from these registry entries. The registry’s sample-size justification for the actual trial is not reported in the registry record.

What is not documented?

The registry contains zero analysis entries. It does not report a statistical analysis plan, a model for the primary endpoint, an approach to outliers or skewed concentrations, a confidence-interval method, or a plan for interim analyses. It also does not report whether the endpoint analysis used all eligible serial-sampling participants or a narrower set beyond the population description. These omissions matter because methods can affect how an estimate is formed and how uncertainty is interpreted. They should not be filled in by assuming standard practice.

In general, pharmacokinetic data can be assessed using methods that account for the shape of concentration data and the sampling structure. Whether such approaches were used is not reported in the registry record. Likewise, no adjustment method for repeated or multiple outcomes is described. The primary endpoint is a defined summary measure, but the absence of an analysis description means its precise derivation from collected data cannot be independently understood from the registry record alone.

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("Serial PK (Subgroup 1)")
n   <- c(27)
m   <- c(2986.28)
sp  <- c(1074.5)
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  Serial PK (Subgroup 1)  27  2986.280  1074.500  2561.222  3411.338

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures, including the primary Cavg endpoint and secondary outcomes covering adverse events, discontinuations due to an adverse event, medically significant laboratory and vital-sign changes, survival status, and invasive fungal infection. It reports zero analysis entries. A multiplicity strategy, such as an order for formal testing or an adjustment for examining multiple outcomes, is not reported in the registry record. In general, when many outcomes are examined, the chance of at least one apparently notable result can increase if each is tested separately; methods for controlling that issue depend on the analysis plan. No such plan is documented.

The primary pharmacokinetic endpoint applies to participants who had serial blood draws on Day 10. The record says Subgroup 2 is excluded because it had a once-daily Day 10 draw for trough determination only. It does not report how many participants met the serial-sampling population definition, how many had usable endpoint data, or whether participants with incomplete sampling were excluded or handled through another method. The enrollment figure does not establish the size of the primary endpoint analysis population.

Missing-data rules, reasons for missing samples, imputation, sensitivity analyses, and the handling of protocol deviations are not reported in the registry record. These details are relevant in general because an analysis based only on participants with complete serial samples may describe a different set of participants from the intended study population if missingness is related to clinical status or treatment experience. The record does not provide enough information to determine whether that concern arose or how it was addressed.

The registry also does not report interim analyses, a prespecified hierarchy among outcomes, or a sample-size justification for the trial’s single-group design. Those methods should not be inferred from the outcome list or the planning illustration. In particular, the planning illustration assumes equal allocation between two arms, whereas the study itself is described as single-group; it is not an observed-power calculation for this trial.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thrombocytopenia (5.7%), cardiac failure (2.9%), respiratory failure (2.9%), agranulocytosis (1.4%), lung infection (1.4%).

The registry reports 15 participants with serious adverse events among 70 at risk in the POS IV group. It also reports 70 participants with events in the other adverse-event category among 70 at risk, and 6 deaths. These fields describe different outcomes and should be read as reported rather than added together. The record does not report whether the same participants contributed to more than one category, and the counts cannot be treated as mutually exclusive.

The selected serious-event terms are thrombocytopenia, 5.7%; cardiac failure, 2.9%; respiratory failure, 2.9%; agranulocytosis, 1.4%; lung infection, 1.4%; and tuberculosis, 1.4%. These percentages are reported as terms in the registry record. The underlying counts for those listed terms are not reported in the registry record, so they should not be reverse-calculated.

In general, adverse-event counts describe events observed during a study and do not, on their own, establish that treatment caused them. This is especially important for a single-group study in a population described as neutropenic and undergoing chemotherapy. The registry does not provide a comparator, event timing, attribution details, or clinical narratives for the deaths in the registry record reported. The figures are therefore descriptive safety information, not a controlled estimate of excess risk or proof of causation.

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

The study’s stated purpose was to characterize intravenous posaconazole pharmacokinetics and safety in Chinese participants at high risk for invasive fungal infections. Its primary endpoint was the steady-state Day 10 average concentration in the serial-sampling subgroup, with a stated objective of assessing the percentage at 500 ng/ml or higher. The endpoint definition and sampling schedule are reported, but the Cavg mean, standard deviation, and threshold-attainment percentage are not reported in the registry record.

That absence prevents a direct reading of the primary pharmacokinetic result. It is not possible from the registry entries to say what average concentration was observed, how much participant-to-participant variation there was, or how precisely the average was estimated. The completed status does not resolve those gaps. Nor does the record establish whether the listed secondary outcomes had results beyond the adverse-event figures and terms included in the safety information.

The safety information records serious adverse events, other adverse events, selected serious-event terms, and deaths. In general, such observations can help describe what occurred during a study, but a single-group design does not provide a concurrent reference for estimating what would have happened under a different treatment or without the study regimen. The registry record also does not establish that an event or death was caused by posaconazole. The figures should be interpreted as descriptive rather than comparative or causal.

The trial does not answer a controlled treatment-effect question. There is no like-for-like comparison group, and the registry explicitly cautions that the arms are not a like-for-like control comparison. The study can be understood as a pharmacokinetic and safety investigation with defined sampling subgroups and an intended continuous exposure outcome. The available record does not show the numerical primary result needed to judge the measured exposure itself.

In short, the registry supports statements about the design, treatment schedule, intended endpoint, sampling approach, and selected safety counts. It does not support a conclusion about the magnitude or precision of Day 10 Cavg, the proportion reaching the stated concentration threshold, or a comparative treatment effect. Those questions remain unresolved in the registry record because the corresponding endpoint results and analysis details are not reported.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between defining a pharmacokinetic endpoint and reporting its result. The record describes Cavg, its calculation from AUC0-24hr and the dosing interval, the Day 10 sampling schedule, and the serial-sampling population. Those details clarify what the investigators intended to measure. But without the mean, standard deviation, or another estimate of uncertainty, readers cannot assess the measured exposure or its precision.

It also shows why analysis populations matter. The primary endpoint is limited to participants with serial Day 10 blood draws, while the sparse-sampling subgroup was intended for trough determination and is excluded from Cavg. Enrollment is not necessarily the same as the population contributing data to a particular endpoint. The registry does not report the size of the endpoint analysis population or how incomplete serial sampling was handled, so the relationship between enrollment and the analyzed data cannot be assessed.

The single-group design is suited to describing measurements under the regimen, but it does not create a concurrent contrast. This distinction prevents descriptive pharmacokinetic observations or event counts from being mistaken for comparative treatment effects. It is also relevant to the listed planning illustration: assumptions involving equal allocation between two arms do not describe the actual single-group design, and planning calculations are not observed power.

Finally, the safety record demonstrates why event counts need context. Serious events and deaths are important observations, but they do not identify cause in the absence of a comparator and attribution information. The registry lists a medically complex, high-risk population and chemotherapy context, while leaving event timing and causal assessment unreported. Statistical interpretation therefore depends not only on which numbers are recorded, but also on the design and the information missing from the record.

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 registry record does not report the primary endpoint value or its standard deviation. It also does not report the percentage of participants whose steady-state Cavg reached 500 ng/ml or higher. This is the central limitation for interpreting the study’s pharmacokinetic objective: the intended measurement is defined, but its observed result is unavailable in the reported details.

The primary analysis population is described by its serial Day 10 blood draws, but the number of participants in that population is not reported. The record also does not state how many samples were missing, whether participants were excluded for incomplete sampling, or how missing endpoint data were handled. The enrollment figure cannot be assumed to equal the endpoint analysis population.

There is no concurrent comparator, and the record identifies the design as single-group. This limits interpretation to descriptive observations and does not support a controlled treatment contrast. The absence of masking is recorded, but the registry does not explain whether outcome assessment could be influenced by knowledge of treatment. That possibility should not be asserted as an observed bias; it is a design feature whose implications depend on the outcome and conduct.

The registry does not report a statistical analysis plan, model, confidence interval, analysis of the threshold objective, multiplicity procedure, interim analysis plan, or sample-size justification for the actual single-group design. It contains zero analysis entries. Although safety counts and selected serious-event percentages are available, event timing, participant overlap, and causal attribution are not reported in the record. The continuation regimen described at investigator discretion is also incomplete in the registry record. Together, these omissions limit evaluation of both the endpoint analysis and the context of safety observations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetics and Safety of Intravenous Posaconazole (MK-5592) in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-120) — NCT03336502.
• Registry record last updated 2019-12-19; status last verified 2019-12.
• Results first posted 2019-12-19.
• 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

NCT03336502 is a completed phase 1, single-group study of intravenous posaconazole in Chinese participants at high risk for invasive fungal infections. The registry lists enrollment as 70, allocation as NA, and masking as none. The described regimen was 300 mg intravenously twice on Day 1, followed by 300 mg once daily on Days 2 to 10 (±1).

The primary endpoint was the Day 10 steady-state average concentration of posaconazole in the serial pharmacokinetic sampling subgroup, summarized as a mean and standard deviation. The registry defines Cavg as AUC0-24hr divided by the dosing interval. The endpoint estimate, standard deviation, and percentage reaching 500 ng/ml or higher are not reported in the registry record. The safety information reports 15 participants with serious adverse events, 70 with events in the other adverse-event category, and 6 deaths; listed serious-event terms include thrombocytopenia and cardiac and respiratory failure. The study has no concurrent comparator, and its results are descriptive rather than a controlled treatment contrast.