Safety, Tolerability, Pharmacokinetic Characteristics of hzVSF-v13 in Healthy Male Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, Pharmacokinetic Characteristics of hzVSF-v13 in Healthy Male Volunteers (NCT03653208), a randomized phase 1 study. The primary outcome is Safety and Tolerability Assessments by Vital Signs.

2. Clinical Question

This is a dose-escalation study in healthy male volunteers, rather than a study of treatment for a clinical condition. Its stated purpose was to investigate safety, tolerability, and pharmacokinetic characteristics after single intravenous administration. The registry names eight dose levels and a placebo group, allowing the study to examine responses across a range of administered doses. The primary outcome concerns participant counts in relation to specified vital-sign criteria. Those criteria cover systolic and diastolic blood pressure and heart rate, including values outside stated thresholds together with changes from baseline.

The central question is descriptive: what safety assessment counts and pharmacokinetic measures were recorded after dosing? The available registry results give arm-level primary outcome counts, but do not provide a dose-by-dose interpretation of changes in vital signs or estimates comparing hzVSF-v13 with placebo. Numeric results for the two named pharmacokinetic outcomes are not reported in the registry record. Therefore, the record does not support a numerical account of how exposure varied by dose or a statistical comparison of safety outcomes between groups.

3. Trial Design

The registry identifies this as a phase 1, randomized, sequential, dose-blocked, double-blind, placebo-controlled, single-dose, dose-escalation study. It lists quadruple masking. The stated intervention was hzVSF-v13 administered intravenously, with placebo as the control. The eight active-dose groups received a single administration on Day 1, at 10mg, 20mg, 50mg, 100mg, 200mg, 400mg, 800mg, or 1200mg. The placebo group also received a single administration on Day 1.

The registry records enrollment of 56 and status as completed. It lists the start date as 2018-11-20 and the primary completion date as 2020-02-29. The primary outcome is described as safety and tolerability assessments by vital signs. Assessments were scheduled from 0 (pre-dose) through 2184 hours post-dose, at the time points listed in the record. The detailed schedule includes frequent early post-dose assessments and later follow-up assessments. The endpoint description sets blood-pressure and heart-rate thresholds and specifies changes from baseline.

The two named secondary outcomes are pharmacokinetic characteristics, specifically Cmax and AUClast. The record does not state the randomization sequence or allocation ratio, nor does it describe how sequential escalation decisions were made. Details of dose-block sizes, dose-escalation stopping rules, participant flow, protocol deviations, or the statistical analysis plan are not reported in the registry record. The arm-level outcome counts include 3 participants in each of the 10mg and 20mg groups, 6 in each of the other active-dose groups, and 13 in placebo. The registry does not explain the relationship between these arm counts and the overall enrollment beyond the recorded group results.

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.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

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.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability Assessments by Vital Signs, measured over 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 336, 504, 672, 840, 1176, 1512, 1848, 2184 hours (post-dose).

The primary endpoint is titled “Safety and Tolerability Assessments by Vital Signs” and is expressed as a count of participants. It concerns systolic blood pressure, diastolic blood pressure, and heart rate. For each measure, the endpoint description identifies an out-of-range threshold together with a change-from-baseline condition. For systolic blood pressure, these include ≤ 90 mmHg with a decrease from baseline ≥ 20 mmHg, or ≥ 140 mmHg with an increase from baseline ≥ 20 mmHg. For diastolic blood pressure, the listed thresholds are ≤ 50 mmHg with a decrease from baseline ≥ 10 mmHg, or ≥ 90 mmHg with an increase from baseline ≥ 10 mmHg. For heart rate, the criteria are ≤ 40 beats/min with a decrease from baseline ≥ 20 beats/min, or ≥ 100 beats/min with an increase from baseline ≥ 20 beats/min.

Repeated vital-sign assessments can describe whether measurements crossed prespecified thresholds during observation, while requiring a change from baseline can distinguish a threshold value from a change occurring during the study. As a general statistical point, counts are a direct way to report how many participants meet a defined event criterion; by themselves, they do not show when events occurred, how long they lasted, or how measurements changed over time. The registry gives assessment time points from pre-dose through 2184 hours post-dose. It does not report separate counts for each vital-sign criterion or time point, so the posted arm-level values cannot be used to reconstruct a detailed pattern of individual measurements or events.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is intended to assign participants to study groups using a chance-based process, reducing the risk that treatment groups differ systematically at the outset. The registry describes this study as randomized and dose blocked, but does not report the allocation procedure, block sizes, or allocation ratio. Those operational details are not reported in the registry record. Randomization alone also does not ensure that baseline characteristics are balanced in a study with small groups; the record does not give baseline characteristics with which to assess balance.

Masking is intended to limit the influence of knowledge about assigned treatment on participant experience, clinical assessment, and outcome recording. The record describes the study as double-blind and lists quadruple masking. It does not specify which people were included in the masking description or how masking was maintained. The placebo comparator provides a control condition, but a randomized placebo-controlled design does not by itself demonstrate that the groups had equivalent outcomes. That requires outcome data and an appropriate comparison.

The sequential, dose-escalation description indicates that dose groups were studied in an ordered escalation context. This design is commonly used in early-phase research to characterize tolerability and pharmacokinetics across dose levels. In general, sequential escalation can make later dosing decisions depend on earlier observations, but the specific decision rules and timing are not reported in the registry record. It would be inappropriate to infer escalation rules, stopping criteria, or the criteria used to select each dose.

The primary endpoint is a participant count based on vital-sign criteria. For a binary outcome, a participant is classified according to whether the defined event occurs, and arm-level results can be summarized as event counts and denominators. General statistical reasoning cautions that counts from small groups are imprecise: changing the outcome status of one participant can alter the count appreciably. An interval estimate can express the uncertainty around an event proportion or group difference. A confidence interval is a range generated by a statistical procedure that reflects sampling uncertainty under its assumptions; narrower intervals generally indicate greater precision. No such interval estimate is reported for the primary outcome in the registry record.

Comparative analysis would ordinarily require a clearly defined outcome, group denominators, and a specified method for estimating the difference or another contrast between dose and placebo. Depending on the design and outcome, methods for binary data may use a risk difference, relative measure, or exact procedure. These are general methodological options, not methods claimed to have been used in this study. The registry does not report a statistical analysis plan or a method for primary-outcome comparisons. The posted arm counts do not yield a reported inferential analysis, and no estimable two-arm binary comparison is available in the posted data.

Pharmacokinetic analyses describe how drug concentration changes over time and summarize exposure. Cmax is the maximum concentration measure, while AUClast refers to area under the concentration-time curve through the last measured time. In general, these measures may be summarized by dose and participant, with variability and uncertainty described using suitable statistics. Numeric results for these outcomes are not reported in the registry record. It is therefore not possible to evaluate their observed values, variability, or dose pattern from the posted results.

Sample-size calculations depend on assumptions about the target effect, variability or event frequency, significance level, allocation, and analysis method. The stated planning assumptions describe an illustration based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning illustrations, not observed power and not a reconstruction of the trial’s design rationale. The trial’s own sample-size justification is not reported in the registry record. Because the posted data do not support an estimable two-arm binary comparison, an effect-based planning illustration should not be treated as a demonstrated treatment contrast.

Multiplicity arises when several outcomes, doses, time points, or comparisons are assessed. Testing many hypotheses can increase the chance of at least one apparently notable result by chance unless the analysis accounts for the testing structure. The registry lists a primary outcome, two secondary pharmacokinetic outcomes, multiple dose groups, and repeated vital-sign assessment times. It does not report whether or how multiplicity was addressed. This general concern does not establish that a particular adjustment was required or omitted; it marks an aspect of the analysis that cannot be assessed from the registry record.

Missing data can affect interpretation when outcome measurements are absent or when participants do not contribute to a particular analysis. The record does not report missingness, handling of missing measurements, or analysis populations. It also does not provide enough information to determine whether all randomized participants contributed to each outcome. These omissions limit assessment of potential bias and the exact denominator for any analysis beyond the arm counts posted.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Group 1 (hzVSF-v13 10mg)", "Group 2 (hzVSF-v13 20mg)", "Group 3 (hzVSF-v13 50mg)", "Group 4 (hzVSF-v13 100mg)", "Group 5 (hzVSF-v13 200mg)", "Group 6 (hzVSF-v13 400mg)")
n      <- c(3, 3, 6, 6, 6, 6)
events <- c(3, 3, 6, 6, 6, 6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Group 1 (hzVSF-v13 10mg)  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Group 2 (hzVSF-v13 20mg)  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Group 3 (hzVSF-v13 50mg)  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Group 4 (hzVSF-v13 100mg)  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Group 5 (hzVSF-v13 200mg)  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Group 6 (hzVSF-v13 400mg)  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary safety and tolerability outcome and two secondary pharmacokinetic outcomes, Cmax and AUClast. The primary outcome was assessed at numerous time points, and the study includes eight active-dose groups alongside placebo. This creates several possible outcome, time-point, and dose comparisons. As a general statistical principle, examining many comparisons can increase the chance of a chance finding if results are selected or interpreted without considering multiplicity. The registry record does not report a multiplicity strategy, such as a prespecified hierarchy, adjustment, or a distinction between confirmatory and exploratory analyses. No conclusion about whether any particular procedure was used can be drawn from the information recorded.

Numeric results for the two secondary outcomes are not reported in the registry record. The primary results are presented as arm-level counts, without time-specific or criterion-specific breakdowns and without comparative estimates. Consequently, it is not possible to assess how the full set of outcomes and time points was analyzed or whether conclusions were based on a prespecified comparison.

The registry does not report the number of missing measurements, reasons for missingness, imputation or other missing-data procedures, or analysis populations. It also does not describe exclusions after randomization or whether all randomized participants were included in each analysis. These details matter because missing measurements can change the denominator and may affect estimates if their absence is related to treatment or outcome. Without the relevant information, the completeness of the outcome data and the sensitivity of results to missingness cannot be assessed. The record’s enrollment and arm-level counts do not replace a participant-flow account or a description of the population used for each endpoint analysis.

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 0% reporting threshold.

The registry reports zero serious adverse events affecting participants in each listed group, including placebo, and records zero deaths in all groups. These are the serious-event figures posted for this study. They are counts, not estimates of the underlying risk of an event. The group sizes are small, so the absence of a recorded serious event in a group does not establish that such an event is impossible or that its risk is zero.

For non-serious adverse events, the registry also records zero affected participants in every group. The record lists participants at risk for these summaries, with group counts of 3, 3, 6, 6, 6, 6, 6, 6, and 13. These are descriptive safety summaries. They do not provide event-specific detail, severity, timing, duration, or a statistical comparison between hzVSF-v13 and placebo. The serious-adverse-event terms list is empty, so no serious event terms are listed in the registry record.

As a general statistical point, zero observed events in a small group leaves uncertainty about the frequency that could occur in a larger population. These results should be read as the reported observations during this study, not as a guarantee about safety in other people, doses, or settings. The registry does not report detailed adverse-event collection procedures or a follow-up-specific analysis.

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

The registry record describes a completed, randomized, masked, placebo-controlled phase 1 study in healthy male volunteers. Participants were assigned across eight single-dose hzVSF-v13 groups or placebo, and the primary outcome concerned vital-sign safety and tolerability assessments. The posted record gives arm-level counts for that outcome and reports zero serious adverse events, zero non-serious adverse events, and zero deaths in each group. These are descriptive observations in the enrolled groups.

Those observations do not establish whether hzVSF-v13 differs from placebo on the primary endpoint. No comparative effect estimate, confidence interval, or hypothesis-test result is reported, and no estimable two-arm binary comparison is available in the posted data. The outcome counts do not show the timing, duration, or criterion-specific pattern of vital-sign events. Nor do the zero adverse-event counts establish that events cannot occur beyond the participants and observation described in the registry.

The registry identifies Cmax and AUClast as secondary outcomes, but does not report their numeric results. Therefore, the record cannot establish the observed pharmacokinetic exposure at any dose or quantify a dose-exposure relationship. The study’s stated objectives are not substitutes for posted results.

More broadly, a phase 1 study in healthy male volunteers addresses a different question from a study of clinical benefit in people with a disease. The registry record does not report evidence about efficacy or clinical outcomes. It also does not give enough information to assess missing data, analysis populations, multiplicity, or the prespecified statistical methods. The appropriate interpretation is limited to the design and the outcome counts recorded. These data do not establish broader safety, effectiveness, or suitability of the intervention for any individual.

14. Why This Trial Matters Statistically

This study illustrates the role of early-phase dose-escalation research in organizing safety, tolerability, and pharmacokinetic assessment across a range of doses. Randomization and masking are important design features because they can reduce bias in treatment assignment and outcome assessment. A placebo group supplies a concurrent reference condition. These design strengths, however, do not guarantee that a registry record will contain enough outcome detail for comparative statistical interpretation.

The trial also demonstrates why endpoint definitions and result presentation matter. The primary endpoint identifies blood-pressure and heart-rate thresholds combined with changes from baseline, and assessment was scheduled repeatedly after dosing. Yet the posted values are arm-level counts without a breakdown by threshold or time. Such summaries are easier to read as counts but provide limited information about the pattern of measurements or the uncertainty around comparisons. In general, detailed outcome definitions, denominators, time-specific results, and uncertainty estimates make it easier to evaluate what a study has observed.

The study has multiple doses and named pharmacokinetic outcomes, making transparent reporting of the analysis plan especially useful for understanding how dose groups, outcomes, and time points were interpreted. The statistical plan and multiplicity approach are not reported in the registry record. Nor are numeric pharmacokinetic findings or comparative primary-outcome estimates. These gaps show that registration information about design and objectives is distinct from a complete account of analyzed results.

For biostatisticians and clinical researchers, the practical lesson is to separate design features, descriptive observations, and inferential evidence. A randomized, masked design supports a framework for comparison, but the comparison still needs an estimate, an uncertainty measure, and a transparent account of the analysis population. When these are absent, interpretation should remain descriptive and acknowledge what cannot be resolved 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 main trial-specific limitation in the registry record is the restricted detail of the posted outcome results. The primary outcome is presented as counts by arm, but not broken down by systolic blood pressure, diastolic blood pressure, heart rate, threshold, or assessment time. The registry therefore does not show when qualifying measurements occurred or whether different criteria contributed to the counts. It also does not explain how repeated assessments were combined into the participant-level outcome.

The group counts are small, including 3 participants in each of the two lowest-dose groups and 6 participants in each of the other active-dose groups. This limits the precision that can generally be expected from group-level safety summaries. The registry does not provide confidence intervals or another measure of uncertainty, and it does not report comparative estimates. No numerical pharmacokinetic results are posted for Cmax or AUClast.

Additional design and analysis details are absent: the randomization procedure, allocation ratio, escalation rules, sample-size justification, statistical analysis plan, multiplicity approach, analysis populations, participant flow, and missing-data handling are not reported in the registry record. The record also does not provide demographic details beyond the population being healthy male volunteers. These omissions constrain assessment of generalizability and of how the reported counts relate to the planned analyses. They do not establish that any particular method was or was not used; they limit what can be verified from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Tolerability, Pharmacokinetic Characteristics of hzVSF-v13 in Healthy Male Volunteers — NCT03653208.
• Registry record last updated 2021-04-27; status last verified 2020-12.
• Results first posted 2021-04-02.
• 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.

19. Record Summary

NCT03653208 is listed as a completed phase 1 randomized, sequential, dose-blocked, double-blind, placebo-controlled, single-dose, dose-escalation study with quadruple masking. The registry reports enrollment of 56 healthy male volunteers. The active intervention was a single intravenous dose of hzVSF-v13 at one of eight listed dose levels, with placebo as the comparator.

The primary outcome was safety and tolerability assessed through vital signs, with specified blood-pressure and heart-rate criteria. The registry posts arm-level primary outcome counts and reports zero serious adverse events, zero non-serious adverse events, and zero deaths in every group. It identifies Cmax and AUClast as secondary outcomes, but numeric results for those measures are not reported in the registry record. Comparative estimates, confidence intervals, the analysis plan, missing-data procedures, and analysis populations are also not reported in the registry record.