Phase I Clinical Trial for Comparison of Pharmacokinetic Characteristics of Vorico Injection 200mg(Voriconazole) and Vfend® IV 200mg for Single Dose Crossover Intravenous Infusion in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase I Clinical Trial for Comparison of Pharmacokinetic Characteristics of Vorico Injection 200mg(Voriconazole) and Vfend® IV 200mg for Single Dose Crossover Intravenous Infusion in Healthy Volunteers (NCT02631954), a randomized phase 1 study. The primary outcome is Cmax of Voriconazole.

2. Clinical Question

In practical statistical terms, the question is whether the concentration summaries after the two products differ, and how precisely that difference is estimated. The posted mean Cmax was 1997 ng/mL for the test group and 2434 ng/mL for the reference group. The recalculated unadjusted mean difference was -436.7 ng/mL, with a 95% confidence interval from -1454.0 to 581.0 ng/mL. The interval includes zero, so these posted data do not establish a clear difference in mean Cmax. That finding is not the same as demonstrating that the products are equivalent: such a conclusion would require a specified margin and an analysis suited to that question, neither of which is reported in the registry record.

3. Trial Design

The registry describes a randomized, unmasked, phase I crossover trial. It lists 24 participants enrolled and healthy volunteers as the study population. The trial compared Vorico Injection 200mg (Voriconazole) with Vfend IV 200mg, with each treatment given as a single intravenous infusion. The registry lists fungal infections, including Aspergillus and Candida infections, among the conditions, but the participants are described as healthy volunteers rather than people being treated for those infections.

A crossover design assigns treatment sequences rather than keeping each participant in just one treatment group throughout. The registry describes a TR sequence in which participants received the test drug, had a 7-day washout, and then received the reference drug. The RT sequence reversed that order: reference drug, 7-day washout, then test drug. The randomized allocation applies to those sequences. This design can allow each participant to contribute observations under both treatments, but the registry record does not report the analysis method used to account for the within-participant structure.

Masking is listed as none. Thus the registry describes the trial as unmasked; it does not report blinding procedures. The trial began in 2015-09, reached primary completion in 2015-10, and is listed as completed. The sponsor was Chong Kun Dang Pharmaceutical.

The primary outcome was Cmax of voriconazole, reported as a mean with standard deviation, in ng/mL. The stated measurement timeframe lists blood-sampling times from 0 through 24 hours. Secondary outcomes listed by name include Tmax, AUCinf, AUCt/AUCinf, Kel, and t1/2. The registry lists seven outcome measures in total. It does not report the original sample-size rationale, detailed eligibility criteria, a formal statistical analysis plan, or the method used to handle the crossover observations. Those details should not be inferred from the sequence description or from the posted summary statistics.

For the primary outcome, the displayed group summaries use 23 participants for each treatment. The registry lists 24 participants enrolled, but does not report participant flow or explain the difference between enrollment and the outcome counts. The summaries therefore describe the posted outcome data rather than a complete account of every participant’s contribution throughout both treatment periods.

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: Subjects who passed the screening were randomized using IWRS before conducting the clinical trail.

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: 24 subejcts were used for baseline analysis.

6. Primary Endpoint

The registry lists the primary outcome as Cmax of Voriconazole, measured over 0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs.

Cmax is the maximum concentration of a drug measured in blood after administration. It is a pharmacokinetic measure: it describes the observed peak concentration over the sampling period, rather than a clinical outcome such as symptom improvement or prevention of disease. The primary endpoint is reported in ng/mL, with the registry specifying that blood samples were analyzed at the listed timepoints from 0 through 24 hours.

Comparing mean Cmax values can describe whether the observed peak concentration summaries differ between formulations under the study conditions. This is useful in a pharmacokinetic comparison because the peak is one aspect of concentration over time. It does not, by itself, describe the full concentration-time profile. Other listed measures, such as Tmax and AUC, address different aspects: timing of the peak and exposure across time.

The registry reports the primary outcome as a mean and standard deviation. The mean gives the average observed Cmax in each group; the standard deviation describes variation among the observations. The posted summaries do not specify whether the reported comparison was based on a paired crossover analysis. They also do not report an equivalence margin. Consequently, the result can be read as an estimate of the difference in the posted mean summaries, but it cannot alone answer whether a prespecified equivalence criterion was met.

7. Results Posted in the Registry

• Test: mean 1,997 versus 2,434 on control; difference -436.70 (95% CI -1,454 to 581.02), standardized effect d = -0.25; z-test p = 0.400.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Tmax of Voriconazole

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Test: mean 1.58 versus 1.57 on control; difference 0.01 (95% CI -0.01 to 0.03), standardized effect d = 0.28; z-test p = 0.337.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Test and the control. The interval gives the range of effects that remain compatible with the data.

AUCinf of Voriconazole

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Test: mean 8,632 versus 8,159 on control; difference 472.26 (95% CI -2,221 to 3,166), standardized effect d = 0.10; z-test p = 0.731.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Test and the control. The interval gives the range of effects that remain compatible with the data.

AUCt/AUCinf

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Test: mean 0.90 versus 0.94 on control; difference -0.04 (95% CI -0.09 to 0.01), standardized effect d = -0.42; z-test p = 0.154.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Test and the control. The interval gives the range of effects that remain compatible with the data.

The registry names five secondary outcomes: Tmax, AUCinf, AUCt/AUCinf, Kel, and t1/2. Numerical summaries are posted for Tmax, AUCinf, and AUCt/AUCinf. Numerical results for Kel and t1/2 are not reported in the registry record. The available secondary measures describe different parts of the pharmacokinetic profile: timing of the peak, overall exposure, and the proportion of exposure observed over the specified period relative to the extrapolated total.

Across the posted secondary comparisons, the estimated mean differences are small in the units of their respective measures, and each unadjusted confidence interval includes zero. This resembles the primary result in the limited sense that none of these summary-based intervals isolates a difference away from zero. It does not establish that all measures are equivalent, nor does agreement among several unadjusted contrasts provide independent confirmation. The outcomes are related aspects of the same concentration-time profile, and the comparisons share the same small trial context.

Multiple secondary outcomes raise a multiplicity issue: when many contrasts are examined, some may appear notable by chance even if no underlying difference exists. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a distinction between confirmatory and exploratory analyses. Consequently, the unadjusted secondary results carry less inferential weight than a prespecified primary analysis would, and they are best treated as descriptive rather than definitive.

The secondary endpoints also cannot compensate for the uncertainty in the primary estimate. AUC measures exposure over time, while Cmax concerns the peak; similar or different patterns across these measures may describe pharmacokinetic features, but they do not answer a clinical outcome question. The healthy-volunteer setting and the absence of reported participant-level or sponsor analyses further constrain broader interpretation. The secondary information adds context, but the registry record does not provide a complete inferential framework for drawing conclusions across all outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Tmax of Voriconazole
• AUCinf of Voriconazole
• AUCt/AUCinf
• Kel (Elemination Rate Constant)
• t1/2

9. Statistical Interpretation

10. Statistical Methods Explained

The posted outcome is a continuous measure summarized using a mean and standard deviation. A mean is the arithmetic average of the recorded values. A standard deviation describes how dispersed individual values are around that average; a larger value indicates greater variability in the observed measurements. These are descriptive summaries. They do not by themselves show how much uncertainty there is in the estimated difference between treatment summaries.

What does the mean difference describe?

The comparison is expressed as the test-group mean minus the reference-group mean. A negative estimate means the posted test mean is lower; a positive estimate means it is higher. For primary Cmax, the estimate is -436.7 ng/mL. This is a contrast between group summaries, not an individual-level change and not a measure of clinical importance. Whether a difference is important for a particular purpose depends on context and, for equivalence questions, on a prespecified margin. No such margin is reported in the registry record.

What does a confidence interval add?

A confidence interval gives a range of values compatible with the data and the calculation method, reflecting sampling uncertainty. In repeated use under the same assumptions, a 95% confidence-interval procedure would capture the underlying quantity in 95% of such intervals. It is not a probability statement that a particular fixed parameter has a 95% chance of lying in this one interval. The primary interval, -1454.0 to 581.0 ng/mL, includes zero and extends in both directions. Its breadth indicates that the posted summary-based estimate is imprecise.

How should the p-value be read?

The unadjusted p-value for the primary contrast is 0.4. In general, a p-value describes how incompatible the observed data, or more extreme data, would be with a specified null model if that model and the calculation assumptions were correct. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. A p-value above a conventional threshold does not demonstrate equivalence. The registry record does not report the sponsor's inferential analysis or its assumptions, so the posted p-value should be read as an unadjusted summary-based calculation.

Why does the crossover design matter?

In a crossover trial, treatment comparisons can use within-participant contrasts because participants may receive both treatments. Observations from the same participant are generally related, and an analysis can account for that pairing, treatment sequence, period, and other design features when appropriate. The registry describes randomized TR and RT sequences and a 7-day washout. It does not report the analysis model, period effects, sequence effects, or participant-level paired data. The recalculated results are simple unadjusted recalculations from posted summary statistics; they do not reconstruct a paired crossover analysis. Thus they should not be presented as the trial's original sponsor analysis.

Why does variation matter?

Variation affects how precisely a mean and a treatment contrast can be estimated. The primary standard deviations are 2457.0 ng/mL in the reference group and 406.2 ng/mL in the test group. This difference in spread is visible in the posted summaries. In general, unequal variability can make a simple comparison less representative of the actual data structure if it assumes a common spread. The registry does not report enough detail to assess the original modeling choices, and the summary-based calculation should not be interpreted as resolving that issue. A standard deviation describes variation among participants; a standard error describes uncertainty in an estimated mean. They answer different questions.

What do the secondary measures represent?

Tmax is the time at which the observed maximum concentration occurs. AUCinf represents area under the concentration-time curve extrapolated to infinity, and is a measure of exposure over time. AUCt/AUCinf is a ratio comparing the area measured over the stated observation period with the extrapolated total. Kel is listed as an elimination rate constant, and t1/2 as a half-life measure. These endpoints complement Cmax by describing timing, exposure, and elimination rather than peak concentration alone. These are general interpretations of the measures; the registry does not report detailed endpoint calculation rules.

The secondary comparisons are also unadjusted recalculations from posted summary statistics. Their p-values and intervals should be interpreted as individual, exploratory contrasts, not as evidence that accounts for all outcomes considered. No multiplicity procedure is reported. There are no reported sponsor analyses in the registry record for the posted secondary outcomes.

What can and cannot be inferred from these methods?

The summaries permit a description of observed means, spread, and unadjusted contrasts. They do not reveal participant-level distributions, missing-data patterns, or within-person correlations. The registry record does not report the original sample-size justification, analysis populations, handling of incomplete measurements, or detailed statistical plan. Those omissions limit assessment of whether the posted calculations match the planned crossover analysis. Any interpretation should therefore keep the randomized crossover design in view while treating these recalculations as summary-based illustrations rather than a reconstruction of the full trial analysis.

11. Confidence Intervals and Precision

The primary mean-difference estimate is -436.7 ng/mL, with a 95% confidence interval from -1454.0 to 581.0 ng/mL. The interval crosses zero and includes possible differences in either direction. It is also broad, so the result leaves substantial uncertainty about the magnitude of the mean contrast. The estimate is not precise enough to identify a narrow range of plausible differences from the posted summary calculation.

Precision is distinct from whether a result is statistically significant. A confidence interval that includes zero means that a zero difference is compatible with the calculation, but it also contains nonzero values. The p-value of 0.4 does not erase the range represented by the interval. Nor does the interval establish that any possible difference is small enough to meet an equivalence criterion. The registry record does not report such a criterion.

Interpretation of precision also depends on the design and calculation. This was a crossover trial, but participant-level paired data and the within-person correlation are not reported. The posted comparison is an unadjusted recalculation from summary statistics, so its interval does not reproduce a full crossover-model interval. The primary group standard deviations differ substantially, which adds a further reason to read a simple summary-based comparison cautiously.

The endpoint summaries include 23 observations in each treatment group, while enrollment is listed as 24. The registry record does not explain the difference or report the participant flow. Without that information, the impact of incomplete data on precision cannot be assessed. Overall, the interval is a useful description of uncertainty in the posted contrast, but not a complete account of uncertainty under every possible analysis of the trial design.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations of the number of participants per arm for 80% power and for 90% power under stated assumptions. They are not a report of the trial's original design calculation. The registry record does not report the original sample-size assumptions or justification. The planning calculation uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It takes the observed effect as a starting point and considers detecting the stated fraction of that effect. For these continuous outcomes, the values are participants per arm, not total event counts.

The 80% power column describes a planning scenario in which the assumed effect would be detected by the specified test in 80% of repeated studies, if the assumptions and effect were correct. The 90% column describes the corresponding 90% planning target. These are design properties under a model, not guarantees about a future study or statements about the current data. The calculations are shown separately for each endpoint because their observed effects and variability differ.

Rows planning for a smaller fraction of the observed effect require more participants: smaller differences are generally harder to distinguish from random variation at the same significance and power targets. The listed counts can therefore rise considerably as the target effect becomes smaller. They are planning illustrations and should not be read as recommendations or as proof that the original trial was adequately or inadequately sized.

This is not observed power. Observed power is not a useful substitute for interpreting the estimated effect and its confidence interval after results are known. The posted trial enrolled 24 participants, while the primary outcome summaries include 23 per treatment. Those observed counts are separate from the hypothetical planning counts.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -436.700; pooled standard deviation σ = 1760.874.
2. n = 2 × (1.96 + 0.842)² × 1760.874² / -436.700² = 255.2, rounded up to 256 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -436.7                      # observed difference in means
sigma <- 1760.87422180007                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2631954)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 256 (80% power), 342 (90% power)
 75% of observed effect: n per arm = 454 (80% power), 608 (90% power)
 50% of observed effect: n per arm = 1,021 (80% power), 1,367 (90% power)
power.t.test: 256.2 
Simulated power at n = 256 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several statistical questions are examined in the same study. The chance of at least one apparently unusual result can increase as more outcomes or comparisons are tested. The registry lists five secondary outcomes in addition to the primary Cmax outcome, and seven outcome measures in total. It does not report a procedure to control multiplicity, a testing hierarchy, or a rule for interpreting secondary findings. The posted secondary p-values are unadjusted, so they should not be interpreted as if they arose from a single isolated test.

The registry record does not report a detailed statistical analysis plan, the sponsor's inferential analyses, or a prespecified equivalence margin. It also does not report the original sample-size justification. Those omissions mean it is not possible to determine from the record which analyses were planned in advance, how the crossover structure was modeled, or how the primary and secondary conclusions were meant to be combined. The posted summary-based recalculations are not a substitute for those missing design and analysis details.

Missing-data handling and analysis populations are also not reported in the registry record. Enrollment is listed as 24, while the posted primary outcome summaries contain 23 observations per treatment. The record does not explain whether this reflects incomplete measurements, a particular analysis population, or another reason. Because the study is a crossover, it would also matter whether participants contributed complete data under both treatments; that information is not reported.

The registry describes randomized treatment sequences and a 7-day washout, but does not report participant-level data, period-specific summaries, sequence-specific results, or the model used to account for within-participant pairing. Nor does it explain how observations affected by missing samples or incomplete periods were handled. These are important omissions for assessing a crossover comparison. They should be treated as unknowns, not filled in by assumptions about usual practice.

15. 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 serious adverse-event summary lists 0 affected participants among 23 at risk in the reference group and 0 among 24 at risk in the test group. Deaths are listed as 0 in both groups. The registry therefore reports no serious adverse events or deaths in these posted group counts. The at-risk counts differ between groups, and the record does not explain that difference.

Other adverse events are listed for 21 of 23 participants at risk in the reference group and 22 of 24 at risk in the test group. These counts are descriptive. The registry record does not provide the event terms, severity breakdown, timing, attribution, or a comparative statistical analysis for these other events. It also does not report further detail about how adverse events were collected or classified.

Zero reported serious events in a small phase I study should not be read as proof that serious events cannot occur. The trial involved healthy volunteers and a single-dose comparison, so these counts do not characterize safety in every population or under other treatment conditions. They describe the adverse-event information recorded for this study, without supporting medical advice or a broad conclusion about safety.

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

The result describes a comparison of pharmacokinetic summaries in healthy volunteers after single intravenous infusions of Vorico Injection and Vfend IV. For the primary Cmax measure, the test-group mean was lower than the reference-group mean in the posted summaries, but the recalculated unadjusted confidence interval includes zero and spans values in both directions. The data therefore do not provide a precise estimate of the difference.

This does not mean that the products have been shown to be the same. A failure to distinguish a difference from zero is not equivalent to demonstrating that any difference is acceptably small. An equivalence conclusion requires a prespecified margin and an analysis designed for that question. The registry record does not report an equivalence margin or the sponsor's inferential analysis.

The result also does not answer whether either treatment improves a clinical outcome. Cmax, Tmax, and AUC measures describe drug concentration and exposure, not recovery from infection or another patient outcome. Although the registry lists fungal infections among the conditions, participants are described as healthy volunteers. The posted findings should not be generalized directly to people receiving treatment for infection.

The crossover design is relevant because the treatment sequences were randomized and each sequence received both products with a 7-day washout. Yet the available recalculation uses group summary statistics and is unadjusted. Without participant-level paired data and the original analysis details, it cannot fully reflect the crossover structure. The registry record also does not explain the difference between 24 enrolled participants and the 23 observations in each primary treatment summary.

In short, the posted data offer a limited description of selected pharmacokinetic measures and adverse-event counts in this phase I study. The primary estimate is uncertain, the secondary results are unadjusted, and several design and analysis details are not reported. These boundaries matter when deciding what the record can support: it describes observed summaries, but does not establish clinical effectiveness, equivalence, or comprehensive safety.

17. Why This Trial Matters Statistically

This trial illustrates why the design and the analysis must be read together. A randomized crossover design can compare two treatments within participants, but the value of that design depends on an analysis that accounts for the paired observations and relevant period or sequence features. The registry supplies the treatment sequences and washout description, yet does not report the inferential model or participant-level information. A summary-based contrast can describe the posted means, but it cannot reveal all the information a crossover analysis would use.

The primary confidence interval also demonstrates the distinction between a point estimate and precision. The estimated mean difference is one value, while the interval shows that the posted summaries are compatible with a broader range of differences. A p-value alone would not convey that range. In a pharmacokinetic comparison, this distinction is especially important when the scientific question may concern similarity rather than simply whether a difference test is statistically significant.

The registry names several related pharmacokinetic outcomes, but secondary results are unadjusted and numerical summaries are not available for every named measure. Considering multiple outcomes without a reported multiplicity plan complicates interpretation. The secondary measures add useful dimensions of the concentration-time profile, but they do not automatically reinforce the primary result.

Finally, the record distinguishes a small phase I study in healthy volunteers from a clinical outcome trial in patients. Its results are relevant as a description of the posted pharmacokinetic and adverse-event summaries under the study conditions. They do not, on their own, answer broader questions about treatment outcomes. This is a useful example of how registry summaries can be informative while still leaving important analysis and interpretation details unreported.

18. 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 immediate limitation is the small number of posted primary outcome observations: 23 per treatment, compared with 24 participants enrolled. The registry record does not explain this difference or provide participant flow. It is therefore not possible to determine why the outcome counts differ, whether measurements were incomplete, or whether the listed summaries represent a particular analysis population.

The comparison is a summary-based unadjusted recalculation, while the design is crossover. The registry does not report participant-level paired observations, within-person correlation, period-specific outcomes, or the original statistical model. As a result, the recalculated interval and p-value may not reflect the analysis that would make full use of the crossover design. The record also does not report a sponsor analysis for comparison.

Other important statistical details are absent: the original sample-size justification, the formal analysis plan, handling of missing data, multiplicity procedures, and an equivalence or non-inferiority margin. Without an equivalence margin, a non-significant difference test cannot establish equivalence. Without an analysis plan, the record does not show which outcomes or methods were prespecified.

The trial was phase I, unmasked, and conducted in healthy volunteers, with single-dose intravenous infusions. These features limit what the summaries can say about other populations, treatment schedules, or clinical outcomes. The registry lists fungal infections as conditions but does not describe a patient treatment outcome. The adverse-event record provides counts but no event terms or detailed comparative analysis. These limitations concern interpretation of the registry record and do not imply that unreported procedures or results did not exist.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Phase I Clinical Trial for Comparison of Pharmacokinetic Characteristics of Vorico Injection 200mg(Voriconazole) and Vfend® IV 200mg for Single Dose Crossover Intravenous Infusion in Healthy Volunteers — NCT02631954.
• Registry record last updated 2020-03-18; status last verified 2016-01.
• Results first posted 2020-03-18.
• 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.

22. Record Summary

NCT02631954 is a completed phase I randomized, unmasked crossover trial sponsored by Chong Kun Dang Pharmaceutical. The registry lists 24 healthy volunteers enrolled. Participants were assigned to treatment sequences comparing single-dose intravenous Vorico Injection 200mg (Voriconazole) and Vfend IV 200mg, with a 7-day washout between treatments.

The primary outcome was mean Cmax of voriconazole. Posted summaries include 23 participants per treatment, and the unadjusted recalculated mean difference is -436.7 ng/mL, with a 95% confidence interval from -1454.0 to 581.0 ng/mL. The interval includes zero and is broad. The registry lists secondary pharmacokinetic outcomes; numerical summaries are not reported for every named outcome.

The record lists no serious adverse events or deaths in either group and reports other adverse events in both groups. The original statistical plan, sample-size justification, analysis populations, missing-data methods, multiplicity procedure, and equivalence margin are not reported in the registry record.