Study to Determine the Safety, Tolerability and Pharmacokinetics of UV-4B Solution Administered Orally in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Determine the Safety, Tolerability and Pharmacokinetics of UV-4B Solution Administered Orally in Healthy Subjects (NCT02061358), a randomized phase 1 study. The primary outcome is Subjects With Treatment-emergent Adverse Event (TEAEs) by Treatment Group.

2. Clinical Question

The primary endpoint counts subjects, not individual adverse-event episodes. A subject with one or more qualifying events is counted once for this endpoint. The registry defines treatment-emergent adverse events as adverse events occurring only after administration of the investigational product.

The design addresses short-term safety and tolerability across the listed dose groups, with placebo as a comparator. It also includes pharmacokinetic outcomes such as peak concentration, time to peak concentration, area under the concentration-time curve, clearance, volume of distribution, half-life, and the amount of UV-4 excreted in urine. Numerical results for these pharmacokinetic outcomes are not reported in the registry record.

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group Phase 1 study of a single ascending oral dose of UV-4B solution in healthy subjects. The registry record lists the study as completed, with enrollment of 64. The listed study dates are 2014-07 for the start and 2015-07 for primary completion.

Eight dose cohorts are described: 3 mg, 10 mg, 30 mg, 90 mg, 180 mg, 360 mg, 720 mg, and 1000 mg. Each cohort description specifies subjects receiving that dose of UV-4B oral solution or placebo. The posted primary outcome entries list 6 subjects for each UV-4B group and 16 for placebo. The record identifies the allocation as randomized, masking as double, and the model as parallel. Details of the randomization procedure, concealment, and how subjects were assigned within cohorts are not reported in the registry record.

The study objective was to evaluate the safety and tolerability of a single ascending oral dose and to determine pharmacokinetic parameters describing absorption and elimination after a single dose. The primary outcome is a safety count, while the listed secondary outcomes concern pharmacokinetic measurements. The registry record does not report a disease-treatment comparison: the participants were healthy subjects, and the condition listed is viral infection.

The record does not describe escalation rules, whether each dose cohort was opened only after review of an earlier cohort, or how dose selection was determined. Those features should not be inferred from the ascending dose sequence alone. The protocol’s sample-size justification and any planned statistical analysis are not reported in the registry record.

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: Each cohort was assigned 6 subjects who received the cohort's prescribed dose of UV-4B, along with 2 subjects in each cohort assigned to receive placebo.

Only the first 6 of 9 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety Population: all subjects who received any investigational product, UV-4B or placebo

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: Total number of randomized subjects in each cohort

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Subjects With Treatment-emergent Adverse Event (TEAEs) by Treatment Group, measured over From time of the first dose administration through Day 9 ± 1.

The primary endpoint is the number of subjects with at least one treatment-emergent adverse event in each treatment group. The observation window begins at the first dose administration and runs through Day 9 ± 1. The registry defines these events as adverse events occurring only after administration of investigational product. The safety population includes all subjects who received any investigational product, UV-4B or placebo.

This count-based endpoint provides a straightforward description of how many treated subjects had one or more events during the specified period. It does not count repeated events separately, describe their severity or duration, or establish whether an event was caused by treatment. Those questions require additional event-level information and clinical interpretation.

The primary outcome entries report 5 of 6 subjects for 3 mg, 6 of 6 for 10 mg, 5 of 6 for 30 mg, 5 of 6 for 90 mg, 6 of 6 for 180 mg, 5 of 6 for 360 mg, 6 of 6 for 720 mg, and 5 of 6 for 1000 mg. The placebo entry reports 12 of 16 subjects. These are observed counts, not estimates adjusted for other factors. The registry record does not report confidence intervals or statistical comparisons for this endpoint.

In general, recording whether a subject experienced any event is useful for summarizing the proportion of participants with at least one event, but a count alone does not capture the full safety profile. Event type, severity, seriousness, timing, and attribution are distinct dimensions. The primary endpoint should therefore be read as a limited summary of reported events within its defined population and timeframe.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary count represent?

The primary endpoint counts subjects with at least one treatment-emergent adverse event. Each subject contributes at most one to the endpoint count, even if that subject experienced more than one event. This is a binary outcome at the subject level: the subject either met the endpoint definition during the observation window or did not. The posted values are counts by group, accompanied by the listed group sizes.

The endpoint’s timeframe is from the first dose administration through Day 9 ± 1. The registry defines treatment-emergent events as adverse events occurring only after investigational product administration. The stated safety population is all subjects who received any investigational product, UV-4B or placebo. The registry record does not give additional rules for handling events with uncertain onset, incomplete follow-up, or missing safety observations.

What can a count comparison tell us?

In general, a count can describe the number of observed subjects meeting an endpoint definition. A comparison between groups is usually expressed through an estimate of the difference or ratio between their event frequencies. Such an estimate is distinct from the underlying counts, and its uncertainty is commonly described with a confidence interval. A confidence interval represents a range of values compatible with the data under the method’s assumptions; it does not guarantee that the true value lies within that particular interval.

No comparative estimate or confidence interval is reported for the primary endpoint in this registry record. The group counts should therefore be read descriptively rather than as a formal test of a treatment effect. In general, small groups can yield uncertain estimates: a change in the outcome of a single subject can materially affect the group summary. That general limitation is relevant when interpreting dose cohorts with 6 listed subjects each, but it does not replace an analysis of uncertainty, which is not reported.

Why does the parallel-group structure matter?

In a parallel-group study, subjects are assigned to one group and outcomes are summarized within that group. The record identifies randomized allocation and double masking, and describes placebo within each dose cohort. Randomization is generally intended to reduce systematic differences between groups at the time of assignment. Masking is generally intended to limit the influence of knowledge about assigned treatment on care, reporting, or assessment. These are general purposes; details of the randomization and masking procedures are not reported in the registry record.

The dose groups are not repeated measurements from the same subjects at multiple dose levels according to the listed parallel-group model. It would therefore be inappropriate to treat the group counts as a within-subject dose sequence. The record does not report a formal trend test or an analysis that pools the dose groups.

What do the pharmacokinetic outcomes measure?

In general, Cmax describes the maximum measured concentration, and Tmax describes when that maximum is reached. AUC measures exposure over a defined time interval; AUC(0-last) refers to the interval through the last measured concentration, while AUC(0-inf) refers to an estimate extending to infinity. Clearance describes elimination in relation to drug exposure, and volume of distribution is a pharmacokinetic quantity relating amount in the body to concentration. The half-life describes the time scale of concentration decline under the relevant pharmacokinetic model. Urinary excretion outcomes describe the amount recovered in urine over an interval or cumulatively.

These are general descriptions of the named measures, not claims about the methods used in this study. The registry record lists the measures but does not provide their numerical results, calculation details, sampling schedule, model specifications, or handling of values that could not be estimated. The methods used for pharmacokinetic analysis are not reported in the registry record.

Why are no significance tests described?

The record reports 0 analyses for the primary endpoint and gives no p-values or confidence intervals. A statistical test, in general, evaluates how compatible observed data are with a specified null hypothesis under stated assumptions. Its result depends on the analysis method and design; it cannot be reconstructed responsibly from a count alone without selecting assumptions and a method that the registry does not report. Recalculations labelled as such are not available for this count endpoint because the registry record does not post a two-arm comparison for it.

The sample-size assumptions described for planning illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those are planning assumptions, not evidence that the trial used that design or analysis. The record does not report the trial’s own sample-size justification, and a planning illustration must not be interpreted as observed power or as a formal trial result.

In general, over-dispersion matters when count outcomes vary more than an assumed statistical model allows. It can make standard errors too small if a model assumes less variability than the data contain. This primary endpoint, however, is a count of subjects meeting a yes-or-no definition, not a count of repeated event episodes. The registry record does not report a model for over-dispersion or a model-based analysis, so no such adjustment should be attributed to this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary safety endpoint and secondary pharmacokinetic outcomes. The secondary outcomes include Cmax, Tmax, AUC(0-last), AUC(0-inf), CL/F, Vz/F, t(1/2), and interval and cumulative urinary excretion of UV-4. Numerical results for these pharmacokinetic measures are not reported in the registry record. The record does not report a hierarchy among secondary outcomes, a multiplicity adjustment, or a prespecified strategy for interpreting multiple comparisons.

Multiplicity is a general concern when many outcomes or comparisons are assessed: the chance of at least one apparently unusual result can increase as the number of tests grows. Whether and how that concern was addressed in this study is not reported in the registry record. The record also does not report a formal comparison of each dose group with placebo, or an analysis of dose trend.

The primary endpoint specifies a safety population of all subjects who received any investigational product. The record lists the group sizes and endpoint counts, but does not describe missing-data rules, the number of subjects with incomplete follow-up, exclusions from the endpoint analysis, or imputation procedures. It does not report whether any subjects were omitted from particular pharmacokinetic analyses or how unevaluable measurements were handled. These details should not be assumed.

In general, missing data can affect an estimate when the likelihood of missingness is related to treatment or outcome. The direction and size of any effect depend on why data are missing and on the analysis approach. Since the registry record does not describe missing observations or their handling, the impact of missingness cannot be assessed from the posted information.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 serious-adverse-event entries report 0 subjects with serious adverse events in each UV-4B group and in the placebo group. The listed numbers at risk are 6 in each dose group and 16 for placebo. These figures summarize the serious-event category as posted in the registry record; they are separate from the primary endpoint, which counts subjects with at least one treatment-emergent adverse event of any reported seriousness.

A reported zero means that no subject in that group was recorded as having a serious adverse event in these entries. It does not mean that every possible adverse event was absent: the primary endpoint entries report treatment-emergent adverse events in each group. Nor does a zero count, particularly in groups with few subjects, establish that the underlying risk is zero. In general, an observed zero in a limited sample leaves uncertainty about events that might occur in a larger population or over a different observation period.

The death fields are not populated with counts. Deaths are therefore not reported in the registry record; they should not be interpreted as a reported count of zero. The registry also lists no top serious-event terms. No further details about specific serious events, event severity, relatedness, or follow-up beyond the stated endpoint timeframe are reported in the registry record.

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

The posted results describe observed safety counts among subjects in this completed Phase 1 study. The primary endpoint records whether a subject experienced at least one treatment-emergent adverse event during the specified period after dosing. The group counts are useful as a basic account of the recorded outcome in these enrolled subjects, but they do not by themselves estimate a precise difference between UV-4B and placebo.

The record does not report confidence intervals, p-values, adjusted comparisons, or another inferential analysis for the primary outcome. It therefore does not quantify how compatible the observed group counts are with a range of possible underlying event rates. The counts should not be presented as proof of a treatment-related difference or as proof of no difference. Similarly, the ascending sequence of dose groups does not establish that adverse-event frequency rises or falls with dose.

The endpoint is limited to subjects with at least one event. It does not convey how many events each subject had, event duration, event severity, or the clinical importance of individual event types. The serious-adverse-event entries report zero affected subjects in all groups, but deaths are not reported in the registry record. Neither finding replaces a complete assessment of all aspects of safety.

The study also aimed to characterize pharmacokinetics, and the record lists several concentration, exposure, elimination, and urinary excretion outcomes. Numerical results for those measures are not reported in the registry record. The safety counts therefore cannot answer questions about absorption, exposure, elimination, or the relationship between dose and measured drug concentrations.

More broadly, this is a study in healthy subjects with a single-dose design. Its registry record does not establish outcomes for repeated dosing, longer-term exposure, or people with viral infection. No medical conclusion about use or benefit follows from these posted counts. The statistical interpretation is limited to the recorded endpoint, the listed groups, and the reported observation period.

13. Why This Trial Matters Statistically

This trial illustrates why the design and endpoint definition matter when reading early-phase clinical data. The primary outcome is a subject-level count of treatment-emergent adverse events, whereas the study’s other stated objective concerns pharmacokinetic characteristics. These are different kinds of evidence: one describes recorded safety events, and the other concerns measured drug exposure and disposition.

The randomized, double-blind, placebo-controlled, parallel-group structure provides a framework for comparing groups, but a design feature alone does not supply a comparative result. For this record, the primary outcome is posted as counts by group, while formal analyses and uncertainty estimates are not reported. Statistical interpretation should separate the observed data from an unreported estimate of treatment difference.

The individual dose cohorts have small listed group sizes. In general, this makes it important to avoid treating a small difference in counts as a stable estimate of what would occur in a broader population. It also makes uncertainty especially relevant, yet no confidence intervals or other precision estimates are reported for the primary endpoint. The record is therefore useful for identifying what was counted and how the groups were organized, but limited for quantifying comparative effects.

The study also shows why absence of a reported serious adverse event is not equivalent to a complete safety conclusion. Serious-event counts are distinct from the broader primary endpoint, and the record does not report deaths as a numerical count. Outcome definitions, populations, and follow-up periods all shape what a safety summary can support.

Finally, the registry lists pharmacokinetic outcomes without numerical results in the record information available for interpretation. That distinction prevents the safety counts from being used as a substitute for exposure data. The statistically careful reading is descriptive and bounded: report the recorded counts, retain the stated endpoint and timeframe, and avoid conclusions that require analyses or measurements not reported in the registry record.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The individual UV-4B groups are small, with 6 subjects listed in each dose group. Small group sizes limit the precision of descriptive comparisons in general, and the registry record does not report confidence intervals to quantify that uncertainty. The placebo group has 16 subjects listed, so the group sizes are not equal in the posted outcome entries.

The registry record provides no inferential analysis for the primary endpoint: the number of analyses is 0, and no p-values or confidence intervals are reported. It also does not report the planned statistical analysis, the sample-size justification, randomization details, or the procedures used to maintain masking. The rationale for the selected doses and any escalation decision process are not reported in the registry record.

The primary endpoint reduces safety information to whether a subject had at least one treatment-emergent event during the stated period. Event-level details needed to assess frequency, severity, duration, type, or attribution are not included in the primary count. The serious-event entries are separately summarized, while death counts are not reported in the registry record.

Although pharmacokinetic measures are listed as secondary outcomes, their numerical results and analysis methods are not reported in the registry record. Missing-data rules, incomplete follow-up, and handling of unevaluable measurements are also not reported. The extent to which any missing observations might influence the endpoint cannot therefore be assessed.

The study concerns healthy subjects and a single-dose design. Its posted record does not establish results for repeated dosing, longer observation, or other populations. The listed condition of viral infection does not change the stated study population, which is healthy subjects. These limitations define the scope of conclusions that can be drawn from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Determine the Safety, Tolerability and Pharmacokinetics of UV-4B Solution Administered Orally in Healthy Subjects — NCT02061358.
• Registry record last updated 2024-03-18; status last verified 2024-03.
• Results first posted 2016-09-01.
• 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

NCT02061358 is a completed randomized, double-blind, placebo-controlled, parallel-group Phase 1 study of a single ascending oral dose of UV-4B solution in healthy subjects. The registry record lists enrollment of 64 and eight UV-4B dose groups ranging from 3 mg to 1000 mg, with placebo as comparator.

The primary endpoint counts subjects with at least one treatment-emergent adverse event from the first dose through Day 9 ± 1. The posted entries report 5 or 6 affected subjects in each UV-4B group and 12 in the placebo group. Serious adverse events are reported for 0 subjects in each group; death counts are not reported in the registry record.

The study also aimed to assess pharmacokinetic measures, but numerical results for those outcomes are not reported in the registry record. No inferential analyses or precision estimates are reported for the primary endpoint. The available outcome information supports a descriptive account of the posted counts, not a formal estimate of comparative treatment effects.