MAD Study Evaluating the Safety, Tolerability, and Pharmacokinetic Effects of N91115 in Healthy Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MAD Study Evaluating the Safety, Tolerability, and Pharmacokinetic Effects of N91115 in Healthy Subjects (NCT02013388), a randomized phase 1 study. The primary outcome is Safety and Tolerability of N91115.

2. Clinical Question

3. Trial Design

The registry describes NCT02013388 as a Phase 1, randomized, double-blind, placebo-controlled, multiple-ascending-dose study in healthy subjects. The study is listed as completed, with a parallel model and quadruple masking. Enrollment is recorded as 49. The registry dates the study start to 2014-02 and primary completion to 2014-12.

The treatment groups covered several dose levels and schedules. The repeated-dose regimens were 10 mg, 50 mg, 250 mg, and 500 mg of N91115, each described as a single oral daily dose for 14 days. The 250 mg repeated-dose regimen was specified as fasted. The record also lists a single oral dose of 50 mg N91115, a daily 250 mg dose for 1 day with a fed fat meal, daily placebo for 14 days, and placebo on Day 1 only. These descriptions indicate that the study included both repeated and single-dose regimens; they should not be read as though every N91115 group followed the same schedule.

Randomization, double blinding, placebo control, and a parallel model are design features recorded by the registry. The record does not describe the randomization sequence, allocation ratio, concealment procedures, the people included in the masking designation, or how masking was maintained. It also does not report a protocol rationale for the chosen doses, the order in which dose groups were studied, or whether the different regimens were intended to support direct comparisons with one another.

The study objective included safety, tolerability, and pharmacokinetic effects. The registry reports safety and tolerability as the primary endpoint, with assessments over 21 Days. It records 5 outcome measures and 0 analyses. The record does not provide a statistical analysis plan or comparative estimates for the primary endpoint, so the study design alone cannot establish what statistical comparisons were planned or how they were to be interpreted.

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 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All patients enrolled in the study were evaluated for safety endpoints

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 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability of N91115, measured over 21 Days.

The primary endpoint is titled “Safety and Tolerability of N91115.” It measures participants, with the unit recorded as participants and the parameter described as a number. The registry says that assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events. The timeframe is 21 Days, and the safety population is described as all patients enrolled in the study.

These measures are used in a Phase 1 study to describe observed safety findings during the assessment period. Clinical evaluations and laboratory assessments can identify findings that meet the study’s criteria for abnormality, while adverse-event monitoring records events reported during the study. They are distinct types of safety information, and a count of participants with a finding does not convey its severity, duration, clinical context, or relationship to treatment unless those details are also reported.

The registry record does not state the criteria used to define an abnormal evaluation or laboratory result, give the detailed categories and time points for all primary endpoint components, or report a single consolidated primary comparison. It also does not describe how findings across these different components were combined, if at all. Consequently, the endpoint title and description identify the general safety domains assessed, but do not by themselves specify a single effect estimate for comparison between N91115 and placebo.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry lists 0 analyses. It does not report an inferential method, a model, an adjustment strategy, or a plan for estimating differences between treatment groups. The posted adverse-event information consists of counts by group. A count is a descriptive statistic: it records how many participants in a group were reported with a specified event category. It does not, by itself, show the uncertainty around the result or test whether groups differ.

What does a confidence interval add?

General statistical explanation: A confidence interval expresses the uncertainty around an estimated quantity, such as a group difference. It describes a range of values compatible with the data under the method’s assumptions. The registry record does not report confidence intervals for the safety results, so the precision of any between-group contrast cannot be read from the event counts alone. Sparse counts can leave considerable uncertainty even when the observed count is zero.

Why does the endpoint structure matter?

The primary endpoint description includes abnormal clinical evaluations, abnormal laboratory assessments, and adverse events. These are different types of findings. A statistical analysis needs to specify what counts as an event, how repeated observations are handled, and whether the components are analyzed separately or combined. The registry record does not report these details or a single comparison for the primary outcome. It explicitly indicates that the primary outcome has several categories or time points and was not reduced to one comparison.

When an endpoint has multiple components, a reader should not assume that a single count represents all of them. Nor should findings from separate components be combined informally: doing so would require clear rules about overlap, time points, and the definition of the outcome. Those rules are not reported in the registry record. The listed event counts are therefore best treated as descriptive results for their named categories.

What is multiplicity?

General statistical explanation: Multiplicity arises when several outcomes, groups, time points, or comparisons are examined. If many statistical tests are conducted, the chance of obtaining at least one apparently unusual result can increase. Analysis plans may address this by specifying a primary comparison, controlling an error rate, or treating additional analyses as exploratory. The registry record does not report how multiplicity was handled, or whether any multiplicity adjustment was planned. Since no analyses are listed, no adjusted or unadjusted test results are available to interpret.

What can the design say about comparisons?

The study is recorded as randomized, double-blind, placebo-controlled, and parallel. These design labels describe features of the study, but they do not supply the missing analysis details. In particular, the record does not report the allocation ratio, the planned contrasts, a statistical model, or whether dose groups were to be compared separately or in another way. Because dosing schedules differ, an appropriate comparison would need to take the groups’ regimens into account; the registry does not report how this was addressed.

General statistical explanation: Randomization can support a fair comparison when the analysis follows the design and the groups are analyzed as planned. It does not eliminate uncertainty, guarantee balance in every characteristic, or make distinct regimens interchangeable. Blinding can reduce some sources of bias, but the masking label alone does not establish whether blinding was maintained in practice.

How should planning illustrations be read?

General statistical explanation: A sample-size calculation is a planning exercise, not a result observed in the trial. The registry record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it also says the effect to detect is a stated fraction of the observed effect. For time-to-event tables, the stated convention is a total number of events; for other calculations, it is participants per arm. Such illustrations depend on their assumptions and should not be interpreted as observed power or as evidence that a comparison was statistically significant. The record does not provide the study’s own sample-size justification.

The registry reports 49 enrolled, but that enrollment figure does not substitute for group-level analysis details. The safety counts have their own numbers recorded at risk for each group. The record does not explain any difference between the overall enrollment figure and the group-specific safety counts, and the counts should not be combined to infer an unreported analysis population. The stated safety population is all patients enrolled, but handling of missing observations is not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy. The primary endpoint covers abnormal clinical evaluations, abnormal laboratory assessments, and adverse events, and the record indicates that the primary outcome has several categories or time points and was not reduced to one comparison. It lists 5 outcome measures and 0 analyses, but does not identify a hierarchy of outcomes, a family of planned comparisons, or any adjustment for multiple testing.

General statistical explanation: When several outcomes or comparisons are examined, multiplicity can affect how strongly individual results should be interpreted. A prespecified strategy can distinguish a primary test from secondary or exploratory analyses and can define how error rates are managed. Without such information, the reported counts remain descriptive; the registry record does not support a claim that a particular comparison was statistically significant or adjusted for multiplicity.

Missing-data methods are not reported in the registry record. The endpoint description says all patients enrolled were evaluated for safety endpoints, but it does not explain whether all measurements were available for every participant, how missing clinical or laboratory assessments were handled, or whether participants with incomplete follow-up were excluded from any component. The reported numbers at risk are given for each adverse-event group, but the record does not explain how those numbers were determined or whether they represent the same analysis population for every outcome.

The registry also does not describe an intention-to-treat analysis, a per-protocol population, or another analysis population for comparative inference. The stated population for safety endpoints is all patients enrolled. No assumptions about missingness, imputation, exclusions, or sensitivity analyses should be inferred beyond that statement.

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 counts are reported by group, together with the number recorded at risk. No participants with a serious adverse event are recorded in placebo (0 of 9 at risk), 10 mg (0 of 6), 50 mg (0 of 6), 250 mg (0 of 6), 500 mg (0 of 6), 50 mg (Single Dose) (0 of 6), 250 mg (Fed) (0 of 6), or Placebo- Single Dose (0 of 4). These are descriptive counts for the registry’s listed groups.

A zero observed count means that no serious adverse event is recorded for that group in these results. It does not establish that the underlying possibility of such an event is zero, and it does not show that groups have equal risks. The group sizes are limited, and the registry record does not report confidence intervals or comparative tests that would quantify uncertainty or support a formal comparison.

Deaths are not reported in the registry record. The serious adverse-event figures should also be kept distinct from the separately listed “other” adverse-event counts. The registry does not define that other category in the information, so it should not be treated as synonymous with a particular severity level or event type. These counts do not provide details about the specific events, timing, duration, severity, or treatment relationship.

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

The registry record describes a randomized, double-blind, placebo-controlled Phase 1 study of N91115 in healthy subjects, with safety and tolerability as the primary endpoint. The posted results give adverse-event counts by group, including no recorded participants with serious adverse events in any listed group. They also give separate counts for other adverse events. These are descriptive observations from the registry, not estimates of a treatment effect supported by a reported comparative analysis.

The results do not establish that N91115 is safe or unsafe, and they do not establish that it is more or less safe than placebo. A zero recorded serious-event count is not proof that serious events cannot occur. The registry does not report confidence intervals, p-values, or adjusted comparisons that would describe the precision of differences. It also does not give the detailed event descriptions needed to evaluate severity, timing, or possible relationships to study treatment.

The trial’s stated objectives include pharmacokinetic effects, but the primary endpoint described in the record is safety and tolerability. The information does not provide pharmacokinetic results. The study’s healthy-subject setting and its different dose schedules also limit how directly these safety counts can be applied to other groups or regimens. No claim about clinical benefit or efficacy follows from these safety data.

For statistical interpretation, the central distinction is between recording events and estimating a comparative effect. The registry provides the former, but does not report the analysis details or estimates needed for the latter. The results are useful as a record of what was counted in each group during the study, while leaving important questions about uncertainty, event definitions, missing data, and between-group differences unresolved.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of why design labels and result counts answer different questions. Randomization, blinding, placebo control, and a parallel model describe how the trial was designed. They do not, by themselves, provide an estimate of a difference between groups. For that, readers also need outcome definitions, a specified comparison, an analysis method, and an account of uncertainty.

The study includes multiple N91115 doses and schedules, alongside placebo regimens that differ in duration. That makes it important to keep each group’s regimen and event count distinct rather than treating all groups as though they were interchangeable. The registry record does not report a comparative analysis plan for these regimens. Its primary endpoint also spans several safety domains and categories or time points, without one reported primary comparison.

The posted serious adverse-event counts are zero for each listed group, but this is not the same as showing no risk. Small group-level counts can provide limited information about uncommon outcomes, and no confidence intervals are reported to express precision. Separate counts for other adverse events further illustrate why event categories and definitions matter: a count is interpretable only in relation to what was included and how it was assessed.

The record also illustrates the distinction between a trial’s stated safety population and the analysis details needed to assess missing observations or comparisons. It says all enrolled patients were evaluated for safety endpoints, but does not report missing-data methods or a statistical analysis plan. Together, these features make careful descriptive interpretation more appropriate than drawing comparative conclusions from the counts alone.

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 gives limited detail about the primary endpoint’s operational definitions. It describes abnormal clinical evaluations, abnormal laboratory assessments, and adverse events, but does not specify the criteria for abnormality, the detailed categories included, or how findings across domains were handled. It also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. This prevents reconstruction of a single primary endpoint estimate from the information reported.

The study contains several dose levels and distinct schedules, including repeated dosing, a single dose, and a fed 250 mg regimen. The registry record does not describe a planned set of comparisons or explain whether these schedules were intended for direct comparison. The result counts should therefore remain tied to their listed groups and should not be interpreted as a common dose-response analysis.

No analysis methods, confidence intervals, p-values, or comparative effect estimates are reported. The record does not describe a sample-size justification, randomization details, handling of missing data, or any sensitivity analyses. Although all enrolled patients are identified as the safety population, the record does not explain the group-specific numbers at risk or whether all endpoint components were observed for every participant.

The serious adverse-event counts are sparse and do not include event descriptions. Deaths are not reported in the registry record. The “other” adverse-event category is not further defined in the information reported, limiting interpretation of those counts. Finally, the study was conducted in healthy subjects, and the registry’s safety results do not by themselves establish findings for other populations, settings, or dosing regimens.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: MAD Study Evaluating the Safety, Tolerability, and Pharmacokinetic Effects of N91115 in Healthy Subjects — NCT02013388.
• Registry record last updated 2016-12-21; status last verified 2016-11.
• Results first posted 2015-03-18.
• 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.

18. Record Summary

NCT02013388 is recorded as a completed Phase 1, randomized, double-blind, placebo-controlled, parallel study with quadruple masking. Its official title describes a multiple-ascending-dose study evaluating safety, tolerability, and pharmacokinetic effects of N91115 in healthy subjects. The sponsor is Nivalis Therapeutics, Inc. Enrollment is listed as 49; the study start is 2014-02 and primary completion is 2014-12.

The primary endpoint is safety and tolerability over 21 Days, based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events. The registry reports group-level serious and other adverse-event counts. It lists 5 outcome measures and 0 analyses, and does not report comparative statistical estimates, confidence intervals, or p-values. The record states that all patients enrolled were evaluated for safety endpoints, while missing-data methods and further analysis-population details are not reported.