Safety and Tolerability Study of N6022 in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability Study of N6022 in Healthy Subjects (NCT01147406), a randomized phase 1 study. The primary outcome is Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, double-blind, placebo-controlled, single-dose escalation study in healthy subjects. The registry record describes quadruple masking and a parallel-group model. The study sponsor was Nivalis Therapeutics, Inc. The record lists the study as completed, with a start date of 2010-08 and primary completion in 2011-06.

The intervention was intravenous N6022, with placebo as the comparator. Posted results are organized into Cohort 1, Cohort 2 and 4, Cohort 3, Cohort 5, Cohort 6, and Placebo. Cohort 2 and 4 are combined in the results, so their findings cannot be separated using the posted record. The dose assigned to each cohort is not reported in the registry record.

The enrollment field reports 41 participants. The primary-outcome results list cohort counts of 6 for Cohort 1, 12 for Cohort 2 and 4, 1 for Cohort 3, 6 for Cohort 5, 6 for Cohort 6, and 10 for Placebo. These are the group counts accompanying the primary result, not a description of how many participants experienced an event. The adverse-event information also reports its own at-risk counts; those counts do not always match the corresponding primary-result group counts.

The study was intended to evaluate safety and tolerability, as well as pharmacokinetics and pharmacodynamic effects according to its official title. A secondary outcome concerns maximum N6022 and metabolite concentrations in plasma within 24 hours of the end of administration. The posted record does not include a pharmacokinetic result or a comparative analysis of the study groups.

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

Analysis population for the primary outcome, as defined in the registry: Any subject that received active IMP 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: Any subject that received any active or placebo

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers, measured over 7 Days.

The primary outcome is titled “Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers.” Its unit is adverse events, and its stated measure is a number. The timeframe is 7 Days. The description includes the number of adverse events reported during the study and also identifies safety variables: changes in vital signs, physical examination findings, telemetry alerts, 12-lead ECG changes, infusion site reactions, O2 saturation changes, and clinical laboratory assessment changes between subjects receiving N6022 and placebo.

Counting adverse events is a descriptive way to record safety observations during an early study. It can show how many events were reported in each listed group, but a count alone does not describe event severity, duration, cause, or whether an individual experienced more than one event. Those details are not reported in the registry record for this primary outcome.

The endpoint is relevant to the stated safety and tolerability objective, but the posted primary result is not a complete account of every listed safety variable. The registry record does not give separate results for vital signs, examinations, telemetry, ECGs, infusion sites, O2 saturation, or laboratory changes. It also does not report a formal comparative estimate for N6022 versus placebo. The reported counts therefore describe the posted endpoint results without establishing a comparative treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes randomized assignment, double blinding, placebo control, quadruple masking, and a parallel-group model. Randomization is a design method intended to reduce systematic differences between assigned groups. Blinding is intended to limit the influence of knowledge about assignment on conduct or assessment. These design features do not by themselves show that groups were similar in every respect, or that an outcome difference is attributable to treatment. The record does not describe how randomization was generated, how allocation was concealed, or which roles were included in the quadruple masking.

What does an event count represent?

A count outcome records how many events were observed according to the outcome definition. It is distinct from a participant count: one person may have more than one event, so the number of events and the number of people affected are not necessarily the same. Here, the primary outcome is stated as the number of adverse events. The separate adverse-event listing reports how many participants were affected by serious or other events. The registry record does not define in detail how recurrent events, event coding, or event attribution were handled for the primary count.

Counts are often interpreted alongside the amount of observation or the number of participants at risk. This context matters because larger groups or longer observation can produce more events even if individual-level event likelihood is similar. The primary results list cohort counts, while the adverse-event listing supplies at-risk counts. Because the at-risk counts for other adverse events do not match all primary-result group counts, care is needed when interpreting the two summaries together. The reason for the differing counts is not reported in the registry record.

Why might count data need a specialized model?

General statistical explanation: count outcomes are nonnegative and can have a distribution unlike a continuous measurement. A count model may be appropriate when its assumptions fit the data and study design. In some count data, variability exceeds what a simple model expects; this is called over-dispersion. If over-dispersion is present and ignored, estimated uncertainty may be too small. Whether over-dispersion was assessed, or whether a count model was planned or used in this study, is not reported in the registry record.

Statistical comparisons of counts may also require a defined observation period and an approach that accounts for differences in exposure time. The primary timeframe is 7 Days, but the registry record does not report exposure-time adjustments or an analysis plan for the count outcome. It is therefore not possible to identify a specific model or assumption set from the posted information.

What does a confidence interval add?

General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity under a specified statistical method. A narrow interval generally indicates greater precision than a wide interval, while both the estimate and interval are needed to assess the range of values compatible with the analysis. No confidence interval or comparative estimate is reported for the primary result, so the precision of a N6022-versus-placebo contrast cannot be assessed from the registry record.

A hypothesis test, if conducted, would address a defined statistical question under its assumptions. A p-value would not measure the size or clinical importance of a difference, nor would it establish that a finding was caused by treatment. No primary-outcome hypothesis test or p-value is reported. The record also does not specify whether an adjusted or unadjusted comparison was intended.

How should the cohort results be handled?

The posted results do not form one clearly defined two-arm count comparison: N6022 results are separated across cohorts, Cohort 2 and 4 are combined, and the record marks a two-arm comparison as unavailable for this count outcome. That limitation is consistent with the displayed structure. Combining the cohorts or calculating a new contrast would require choices about the analysis population, dose groups, and event definition that are not stated in the registry record. No such recalculation is presented.

The study’s official title describes an ascending-dose design, but the registry record does not report the dose assigned to each cohort or the planned statistical method for comparing dose groups. It also does not report a sample-size justification, interim analyses, or a prespecified analysis plan. Consequently, the cohort-specific counts are best read descriptively, without inferring a dose-response relationship or a formal between-group result.

10. Multiplicity, Missing Data and Analysis Populations

The registry record reports one primary outcome and a secondary outcome concerning maximum N6022 and metabolite concentrations in plasma within 24 hours of the end of administration. It does not report a multiplicity strategy, such as how testing across outcomes or cohorts would be controlled. The number of analyses reported is 0, and no inferential analyses or comparative estimates are posted. Whether analyses were conducted but not entered in the registry record is not reported there.

The primary outcome includes multiple kinds of safety information, including adverse events and changes in vital signs, physical examination findings, telemetry alerts, 12-lead ECGs, infusion site reactions, O2 saturation, and clinical laboratory assessments. The record does not specify how these components were combined or whether each was analyzed separately. It does not identify a hierarchy of outcomes or report how any multiplicity would be handled.

The analysis population for the primary outcome is described as any subject who received active IMP or placebo. This is not the same as a detailed accounting of all randomized participants. The registry record does not report exclusions, withdrawals, missing observations, treatment discontinuations, or the handling of incomplete safety assessments. It also does not state whether all randomized participants were analyzed according to their assigned group or according to treatment received.

The adverse-event listing gives at-risk counts, but the record does not explain differences between those counts and the group counts accompanying the primary result. Missingness and denominator definitions therefore cannot be fully evaluated. No imputation method or sensitivity analysis is reported in the registry record.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious-adverse-event listing reports 0 affected participants in Cohort 1, Cohort 2 and 4, Cohort 3, Cohort 5, Cohort 6, and Placebo. It also reports zero serious events among the participants listed as at risk in each group. The top serious adverse-event terms list is empty. Death counts are not reported in the registry record.

These entries describe what the registry record reports; they do not establish that the risk of a serious event is absent. Safety summaries from a study of this size can only describe events observed among the participants followed. The record does not report confidence intervals or a comparative analysis for serious adverse events, so it does not quantify the precision of a difference between groups.

The separate listing for other adverse events reports affected participants, not event counts. It reports 1 affected participant in Cohort 1, 4 in Cohort 2 and 4, 1 in Cohort 3, 0 in Cohort 5, 1 in Cohort 6, and 2 in Placebo. The placebo at-risk count for other events is 6, while the primary-result group count for Placebo is 10. The record does not explain this discrepancy in denominators. Serious-event and other-event entries should therefore be read as distinct summaries, and not substituted for the primary endpoint count.

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

The posted results provide a descriptive account of adverse-event counts across the N6022 cohorts and placebo, alongside a separate listing of participants affected by serious and other adverse events. They show that the registry record reports no serious adverse events in the listed groups and reports other adverse events in several groups. The primary endpoint values are counts of events, whereas the safety listing’s affected values are counts of participants; the two measures answer different descriptive questions.

The record does not provide an inferential comparison between N6022 and placebo. There are no reported estimates of a between-group difference, uncertainty intervals, or hypothesis-test results. The cohort structure and missing dose details also prevent a clear dose-specific interpretation from the registry record. The outcome counts alone do not establish a treatment effect or causal attribution.

These results do not demonstrate that N6022 is safe or unsafe. They do not establish that N6022 changes the occurrence of adverse events relative to placebo, and they do not show that the groups are equivalent. Such conclusions would require an analysis with a clearly defined comparison and suitable uncertainty assessment, neither of which is reported in the registry record.

The study’s stated objective was to evaluate safety and tolerability in healthy subjects. The posted information is limited to the reported counts and does not supply details on event severity, timing, relatedness, or resolution. Nor does it provide results for the other safety variables listed in the endpoint description or the secondary pharmacokinetic outcome. Accordingly, the record supports a narrow reading of the reported observations, rather than a broad conclusion about safety, pharmacokinetics, or clinical use.

13. Why This Trial Matters Statistically

This study illustrates why a count and a comparison are not the same statistical result. The registry record gives primary-outcome event counts across several cohorts and placebo, but it does not report a single N6022-versus-placebo estimate. Without that estimate and its uncertainty, readers cannot determine how precisely the observed groups differ or whether a formal statistical comparison was made.

It also illustrates the importance of distinguishing events from affected participants. A participant may contribute more than one event, so the primary endpoint’s count and the separate number of participants affected by other adverse events should not be conflated. Denominators matter as well: the primary results and the adverse-event listing do not report identical group counts for every category, and the reason is not given.

For a multi-cohort study described as ascending-dose, dose-specific results are important for interpreting patterns across dose levels. The registry record labels cohorts but does not report their dose levels, and it combines Cohort 2 and 4. That limits dose-response interpretation. It also underscores the value of reporting a prespecified analysis plan, outcome definitions, analysis populations, and uncertainty measures. Those details are not reported in the registry record.

These are general statistical considerations, not additional findings about N6022. They explain why a descriptive early-study safety record is useful for documenting observations while remaining insufficient for a definitive comparative conclusion.

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 registry record does not report the N6022 dose levels assigned to the cohorts, despite describing an ascending-dose study. Cohort 2 and 4 are presented together, so their results cannot be distinguished. The posted data therefore do not support dose-specific interpretation or evaluation of a dose-response pattern.

The primary outcome is stated as a number of adverse events, but event-level detail is not reported. The registry record does not provide event terms, severity, timing, duration, relatedness to study intervention, or resolution for the primary result. It also does not report results separately for the other safety variables named in the endpoint description.

The primary-result group counts and the adverse-event listing’s at-risk counts differ for some categories, including Placebo. The record does not explain the denominator differences or provide an account of missing observations and exclusions. The number of participants enrolled is reported as 41, while the primary results and adverse-event groups are presented separately; the record does not reconcile these summaries.

No inferential analysis, comparative effect estimate, confidence interval, or p-value is reported. The statistical plan, sample-size justification, interim analyses, and multiplicity approach are not reported in the registry record. Death counts are also not reported. These limitations prevent assessment of comparative precision and leave several aspects of the safety data and analysis population unclear.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Tolerability Study of N6022 in Healthy Subjects — NCT01147406.
• Registry record last updated 2014-03-07; status last verified 2014-01.
• Results first posted 2014-03-07.
• 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

NCT01147406 is a completed Phase 1 randomized, double-blind, placebo-controlled study of single ascending intravenous doses of N6022 in healthy subjects. The record describes quadruple masking and a parallel-group model, with an enrollment of 41. Its primary safety outcome concerns adverse events during 7 Days and includes several additional safety variables in the outcome description.

The posted primary results give event counts for Cohort 1, Cohort 2 and 4, Cohort 3, Cohort 5, Cohort 6, and Placebo. A separate safety listing reports no participants affected by serious adverse events and provides counts for other adverse events. No comparative statistical analysis is reported. Dose levels, detailed event characteristics, and explanations for differing at-risk counts are not reported in the registry record.