Safety, Tolerability and Activity of SRX246 in Adults With Intermittent Explosive Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and Activity of SRX246 in Adults With Intermittent Explosive Disorder (NCT02055638), a randomized phase 1, phase 2 study. The primary outcome is Safety and Tolerability.

2. Clinical Question

The trial asked whether SRX246 could be studied for safety, tolerability, and activity in adults with intermittent explosive disorder (IED), with placebo as the comparator. Its primary outcome was titled “Safety and Tolerability” and measured participants with adverse events. The registry record does not provide a single comparative estimate for that outcome.

3. Trial Design

The registry classifies NCT02055638 as a randomized, quadruple-masked, parallel-group study, listed in Phase I and Phase II. A total enrollment of 97 is recorded. Azevan Pharmaceuticals is named as the sponsor. The record gives a start date of 2014-05, primary completion of 2016-05, and status “COMPLETED.”

The study description says adults with a current IED diagnosis entered a two-week baseline lead-in phase. Participants who continued to meet enrollment criteria were then randomized to SRX246 or placebo. The two groups received capsules over an eight-week period: the SRX246 schedule began at 120mg twice daily for 4 weeks and then changed to 160mg twice daily for 4 weeks; the placebo schedule was intended to match the amount of SRX246 capsules for 8 weeks.

Weekly scheduled visits included examinations and questionnaires. The brief study description says results would be based on changes observed over the study period, but it does not identify all measures or the planned methods for assessing those changes. The primary safety outcome is specified for the intent-to-treat population and spans from the first intervention dose through study completion, up to 8 weeks.

The registry record identifies two outcome measures, but no analysis results are listed. The record does not report the randomization procedure, how allocation was concealed, the specific roles covered by quadruple masking, or how masking was maintained. It also does not report the planned statistical analysis in sufficient detail to establish how the investigators intended to compare 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.

Before assignment: One additional subject was enrolled than planned, due to timing of screening and notification to sites of ceasing planned enrollment.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent to treat

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.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability, measured over from initial dose of intervention until completion of the study up to 8 weeks.

The primary outcome is titled “Safety and Tolerability.” It measures the number of participants with adverse events, from the initial dose of the intervention until study completion, for up to 8 weeks. The listed population is intent to treat. In practical terms, this outcome describes how many participants in each randomized group had at least one recorded event, rather than the total number of event episodes.

Counting participants with events is a direct way to summarize whether participants experienced adverse events during the specified observation period. It can help readers distinguish event experience from other dimensions, such as event severity, duration, or recurrence. Those details are not captured by a simple count of participants, and the registry record does not report a detailed event-by-event analysis for this outcome.

The posted record separately gives serious adverse event counts and counts for other adverse events. For other adverse events, it records 9 participants in the SRX246 group and 7 in the placebo group. It records no serious adverse events in either group. These are descriptive counts, not a reported adjusted comparison or a complete account of the primary endpoint’s statistical analysis. The record does not report a confidence interval or a formal test for the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help turn observed outcomes into estimates that can be interpreted in relation to uncertainty, study design, and the question being asked. The registry record for this trial does not list analysis results, so the explanations below distinguish general statistical principles from methods documented for this particular study.

What does randomization contribute?

In general, random allocation is intended to reduce systematic differences between treatment groups at the start of a study. It does this by making group assignment independent of participants’ known and unknown characteristics in expectation. Randomization does not guarantee identical groups in the realized trial, particularly when group sizes are limited. The registry identifies this study as randomized, but the particular randomization procedure and allocation-concealment method are not reported in the registry record.

A parallel-group design assigns participants to a group and follows that group over the study period. The registry identifies a parallel model with SRX246 and placebo groups. Quadruple masking is also recorded, but the registry record does not specify which people were masked or describe the procedures used to preserve masking. General statistical interpretation should therefore acknowledge the design label without assuming implementation details.

What does a participant count represent?

The primary outcome is defined as the number of participants with adverse events. For a binary participant-level outcome, each participant is classified according to whether the event definition was met during the observation period. This differs from counting every event episode: a participant with repeated events may still contribute as one participant with an event in a participant-count summary. The posted adverse-event counts are separated into serious and other categories, and the registry identifies the primary outcome population as intent to treat.

In general, a group count needs a denominator to convey how many people were observed and at risk. The registry lists 49 participants at risk in the SRX246 group and 48 in the placebo group for the serious and other event summaries. The primary outcome timeframe is from initial dose to study completion, up to 8 weeks. A denominator and timeframe make a count more interpretable, but they do not supply information about event duration, severity, repeated episodes, or when events occurred.

Why would an estimate need an interval?

In general, a confidence interval describes a range of values compatible with the observed data under a specified statistical procedure. It communicates uncertainty around an estimate, rather than proving that a particular value is correct. Wider intervals generally indicate less precision, while narrower intervals indicate greater precision under the same inferential framework. The registry record does not report a confidence interval for the adverse-event outcome, so the precision of a comparative effect cannot be evaluated from the posted counts alone.

A hypothesis test and a confidence interval answer related but distinct questions. A test assesses the data against a specified null hypothesis under a model and a chosen significance threshold. An interval expresses uncertainty over a range of possible effects. Neither a test nor an interval resolves questions of clinical importance, outcome completeness, or bias. No test statistic, p-value, or comparative interval for the primary outcome is reported in the registry record.

Why might modeling choices matter?

General methods for binary outcomes can compare event probabilities, estimate a difference or ratio, or adjust for prespecified covariates. Each approach targets a particular effect measure and relies on assumptions. For example, adjustment requires a defined model and variables; a model-based estimate is not interchangeable with a raw count. The registry record does not report which effect measure or model was planned, whether covariate adjustment was intended, or whether assumptions were checked.

When outcomes are counts of event episodes rather than participants with at least one event, repeated events can create a different statistical problem. In general, over-dispersion means the observed variability is greater than a model assumes; accounting for it can affect uncertainty estimates. This concept should not be confused with the current participant-count definition. The registry does not report an event-episode model or an over-dispersion analysis.

What do the planning illustrations mean?

General sample-size planning estimates how many participants may be needed to detect a specified effect under stated assumptions. The registry’s planning description says its illustrations use the observed effect, equal allocation, a two-sided significance level of 0.05, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These calculations are planning illustrations, not observed power, and they are not evidence that the trial was originally designed using those assumptions. The registry record does not report its original sample-size justification. No planning count should be interpreted as the number actually observed in an arm.

The planning description distinguishes participant counts per arm from total event counts for time-to-event illustrations. That distinction reflects that different outcome types use different units of analysis. The primary outcome described for this trial is a count of participants with adverse events, not a time-to-event outcome. The registry record does not report a time-to-event analysis for this primary safety outcome.

How should missingness and multiplicity be considered?

In general, missing outcome data can affect estimates if participants with unobserved outcomes differ in relevant ways from those with observed outcomes. Appropriate handling depends on why values are missing and on the analysis plan. An intent-to-treat label generally refers to analyzing participants according to randomized assignment, but it does not by itself explain how unavailable outcome information is handled. The registry record does not report missing-data counts, reasons, imputation, or sensitivity analyses.

Multiplicity arises when several outcomes, categories, time points, or comparisons are examined. Multiple analyses can increase the chance of a seemingly notable result arising by chance if interpretation does not account for the analysis structure. The registry indicates that the primary outcome has several categories or time points and was not reduced to one comparison. It does not report a multiplicity strategy, prespecified hierarchy, or analysis results. Those omissions limit what can be concluded from the posted record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies two outcome measures, but no analyses are listed. It also notes that the primary outcome contains several categories or time points and is not reduced to one comparison. The record does not specify a hierarchy among outcomes, explain how multiple comparisons were handled, or report an adjustment for multiplicity. Without those details and without posted analysis results, the record does not support a single inferential conclusion about the primary outcome.

The primary population is described as intent to treat. In general, an intent-to-treat approach analyzes participants according to randomized assignment, preserving the comparison created by randomization. The label alone does not reveal how participants with missing outcome information were treated. The registry record does not report missingness by group, reasons for missing data, imputation methods, or sensitivity analyses.

These omissions matter because missing outcomes and multiple analyses can affect interpretation of estimates and uncertainty. A complete assessment would need to specify which outcome definitions and time points were analyzed, how incomplete observations were addressed, and what comparison was prespecified. Those details are not reported in the registry record. The posted event counts remain useful descriptive information, but they cannot replace a clearly specified analysis plan or a reported analysis.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports no serious adverse events among 49 participants at risk in the SRX246 group and no serious adverse events among 48 participants at risk in the placebo group. It also reports no deaths in either group. For other adverse events, the record lists 9 participants in the SRX246 group and 7 in the placebo group. These categories are reported separately and should not be conflated.

Zero recorded serious events means that none are listed for the observed participants and period; it does not establish that the underlying risk is zero. With no reported interval or formal comparison, the precision of the serious-event estimate cannot be assessed from the registry record. The other-event counts are descriptive and do not indicate causality. The record does not provide event-specific descriptions, severity details for other events, timing, recurrence, or a formal statistical comparison. The primary outcome timeframe is from initial dose through study completion, up to 8 weeks.

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

The registry record documents a randomized, quadruple-masked, parallel-group comparison of SRX246 and placebo in adults with IED. It records 97 participants enrolled and describes an eight-week intervention period after a two-week baseline lead-in for participants who continued to meet enrollment criteria. For safety, the posted counts show 9 participants with other adverse events in the SRX246 group and 7 in the placebo group; serious adverse events and deaths are recorded for 0 participants in each group.

These observations describe what the registry reports, but they do not establish that one group had more or fewer events in a statistically reliable sense. No comparative estimate, confidence interval, p-value, or analysis result for the primary endpoint is listed. The record itself indicates that the outcome has several categories or time points and is not reduced to one comparison. No treatment-effect claim can be inferred from the event counts alone.

The counts also do not establish whether events were caused by SRX246 or placebo, how severe the other events were, whether some participants experienced repeated events, or when events occurred. They do not describe outcomes beyond the stated observation period. The registry record does not report enough detail to assess missing-data handling, multiplicity, or the specific analysis population for each posted event count.

In general, a trial result is interpreted in light of its design, outcome definition, analysis, uncertainty, and completeness of follow-up. The record identifies randomization and masking but does not report all implementation details or a statistical analysis plan. The planning illustrations described in the registry are not observed power and do not establish that the trial was adequately sized for a particular safety or activity question. The original sample-size justification is not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable as a randomized, masked, parallel-group study with a placebo comparison and a clearly described safety outcome timeframe. The registry also supplies participant counts at risk and separates serious from other adverse events. Those features allow readers to understand the basic structure of the posted safety information rather than relying on an undifferentiated event total.

At the same time, the record illustrates why event counts alone are not a complete comparison. The primary outcome is described as involving several categories or time points, and no single comparison is reported. The registry lists no analysis results, confidence intervals, or formal tests for the primary endpoint. As a result, the counts offer descriptive context, but their statistical precision and comparative meaning remain unclear.

The distinction between a planned sample-size illustration and observed study evidence is also important. The registry describes illustrations based on the observed effect under specified assumptions, but these are not observed power and are not the trial’s original design justification. The original justification is not reported in the registry record. Planning calculations cannot substitute for estimates with uncertainty from the trial’s actual outcome data.

Finally, this record underscores the value of transparent reporting about outcome definitions, missing data, multiplicity, and analysis populations. Without those details, readers can identify the design and the reported event counts, but cannot fully reconstruct the inferential analysis or judge how robust a comparative conclusion would be.

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 offers limited detail for interpreting the primary safety endpoint. It identifies the outcome as the number of participants with adverse events, names the intent-to-treat population, and specifies a timeframe up to 8 weeks. However, the record does not provide a single comparison for this outcome because it includes several categories or time points. No analyses are listed, and no comparative effect estimate or uncertainty interval is reported.

For the event counts, the record does not describe the specific other adverse events, their severity, timing, duration, recurrence, or relationship to study intervention. It reports serious and other event counts separately, but does not explain how events were collected, coded, or adjudicated. The record also does not report missing outcome information or how incomplete observations were handled.

Some trial-design details are also absent. The registry does not report the randomization procedure, allocation concealment, the specific people included in quadruple masking, or how masking was maintained. It does not provide the planned statistical analysis, multiplicity approach, or the trial’s original sample-size justification. The posted planning assumptions are not a substitute for those protocol details.

These limitations constrain interpretation of the safety counts and prevent a full reconstruction of the planned or performed statistical comparison. They do not change the descriptive values recorded in the registry, but they restrict conclusions about precision, comparative effects, and the broader pattern of adverse events.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability and Activity of SRX246 in Adults With Intermittent Explosive Disorder — NCT02055638.
• Registry record last updated 2023-07-21; status last verified 2023-07.
• Results first posted 2019-10-29.
• 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

NCT02055638 is a completed, randomized, quadruple-masked, parallel-group Phase I and Phase II study sponsored by Azevan Pharmaceuticals. The registry records 97 participants enrolled and compares SRX246 with placebo in adults with IED. The study description includes a two-week baseline lead-in followed by an eight-week intervention period for participants who continued to meet enrollment criteria.

The primary outcome is safety and tolerability, measured as the number of participants with adverse events through study completion, up to 8 weeks, in the intent-to-treat population. The record lists 9 participants with other adverse events in the SRX246 group and 7 in the placebo group; serious adverse events and deaths are recorded for 0 participants in each group. No analyses are listed, and the primary outcome is not reduced to one comparison. The registry record does not report a comparative estimate or the details needed to assess its precision.