Exploratory Study to Evaluate the Effect of SYN111 (Rufinamide) in Patients With Generalized Anxiety Disorder (GAD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Exploratory Study to Evaluate the Effect of SYN111 (Rufinamide) in Patients With Generalized Anxiety Disorder (GAD) (NCT00595231), a randomized phase 2 study. The primary outcome is Change From Baseline in Hamilton Anxiety Scale (HAMA) - Total Score: Summary Statistics - Observed.

2. Clinical Question

The trial is described as randomized, placebo-controlled, and exploratory. Its central statistical comparison is between the HAMA total-score change among participants assigned to rufinamide and the change among those assigned to placebo. A lower follow-up score would represent fewer reported anxiety symptoms on this scale, but the registry record does not include the numerical changes or a between-group estimate. It therefore does not establish the size or precision of any difference between treatment groups.

The registry lists 239 participants enrolled. That is the trial’s overall enrollment figure; it should not be treated as the number assessed for the primary outcome at 8 Weeks, because outcome-specific counts are not reported. The record also lists six outcome measures, while the primary outcome is described as an observed summary measure. Without arm-specific results, uncertainty estimates, and outcome counts, the clinical question remains unanswered by the numerical results in the registry record.

3. Trial Design

This was a completed Phase 2 exploratory study of rufinamide in generalized anxiety disorder. The registry lists randomized allocation and a parallel-group model, with placebo as the comparator. The official title describes the study as multi-center, randomized, double-blind, and placebo-controlled; the registry’s masking entry is triple. These descriptions are both part of the record, and the record does not explain their difference.

The trial enrolled 239 participants. The rufinamide arm is described as receiving 500 mg for 1 week, followed by 1000 mg for 7 weeks. The placebo arm received 0 mg tablets. The primary outcome timeframe is 8 Weeks, which corresponds to the stated treatment schedule. The registry gives a start of 2008-03, a primary completion of 2008-10, and a status of completed.

The primary outcome was change from baseline in the HAMA total score, reported as a mean with standard deviation. The endpoint description defines the analysis population as the ITT Population: randomized participants who received at least one dose of study drugs. It does not state how many participants met this definition or contributed an 8-Week measurement.

The record lists six outcome measures but no analysis records. It does not report the sequence of outcome assessments beyond the primary endpoint timeframe, the randomization procedure, allocation concealment, site count, treatment adherence, or sample-size justification. It also does not describe an interim-analysis plan. These details cannot be inferred from the phase, allocation, or masking labels. As an exploratory study, its title signals an investigative aim, but the registry record does not set out a confirmatory testing framework or a prespecified threshold for clinical importance.

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: ITT Population: Randomized and received at least one dose of the study drugs.

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: ITT Population: Randomized and received at least one dose of the study drugs.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Hamilton Anxiety Scale (HAMA) - Total Score: Summary Statistics - Observed, measured over 8 Weeks.

The primary endpoint is change from baseline in the HAMA total score at 8 Weeks. HAMA is an interviewer-rated measure intended to describe the severity of anxiety symptoms. It contains 14 items: seven address psychic anxiety, such as mental agitation and psychological distress, and seven address somatic anxiety, or physical complaints related to anxiety. Each item is rated on a 5-point scale, and the total score is the sum of items 1–14.

The total score ranges from 0 to 56. The endpoint description classifies scores of 17 or less as mild anxiety severity, 18 to 24 as mild to moderate, 25 to 30 as moderate to severe, and 31–56 as very severe. These ranges help describe the scale’s score levels; they do not, on their own, define how much change would be important to an individual or establish a treatment effect.

Change from baseline is used to express how a participant’s score differs from their starting measurement over the assessment period. Comparing average changes between randomized groups can describe the difference in observed score trajectories while accounting for each participant’s baseline value in the change measure. The registry identifies the statistic as a mean and its dispersion as a standard deviation. It does not report the group means, standard deviations, or a direct between-group estimate, so the magnitude and precision of the primary endpoint comparison are not available in the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary measure represent?

The HAMA total score is a continuous measure: it can take values across a numerical scale, and the primary outcome is expressed as a mean. The record describes 14 interviewer-rated items, with seven psychic-anxiety items and seven somatic-anxiety items. Summing all items gives a total from 0 to 56. Change from baseline refers to the follow-up score in relation to the participant’s starting score. The record does not provide the calculation details used to obtain each participant’s change or the group summaries that resulted.

What does a mean and standard deviation tell a reader?

In general, a mean describes the center of a set of numerical observations, while a standard deviation describes how spread out those observations are around the mean. They answer different questions: the mean describes an average score or average change, and the standard deviation describes participant-to-participant variability. Neither statistic alone gives the uncertainty of a comparison between randomized groups. For that, an estimate of the contrast and an uncertainty measure, commonly a confidence interval, are useful. The registry record names mean and standard deviation as the summary statistics but does not report their values for the primary endpoint.

Why is the between-group comparison important?

In general, change within one arm is not by itself a randomized treatment comparison. Participants in either arm may show changes over time for reasons that are not specific to assignment. A contrast between the randomized groups is the relevant summary for describing how their observed outcomes differ under the study conditions. Its interpretation depends on the analysis population, the handling of incomplete measurements, the selected outcome and time point, and the statistical model. Those details, along with the actual primary contrast, are not reported in the registry record.

What does randomization contribute?

Random assignment is intended to create groups that are comparable on average at the start of a trial, including with respect to factors that may affect outcomes. It does not guarantee that every characteristic will be identical between groups, especially in any individual trial. The record identifies the allocation as randomized and the model as parallel, so participants were assigned to one of the study groups rather than described as crossing between them. The method used to generate the assignments and conceal them is not reported in the registry record. The official title describes double blinding, while the masking entry says triple; the record does not clarify which roles were masked.

What can be said about uncertainty?

In general, a confidence interval gives a range of effect estimates compatible with the data and the method’s assumptions. A narrower interval indicates greater precision than a wider interval, but interpretation also depends on the endpoint and on what differences would matter clinically. A p-value, when used, summarizes how unusual data at least as incompatible with a null hypothesis would be under the statistical model if that null hypothesis were true. It does not measure the probability that a treatment is effective, nor does it communicate the size of an effect. The registry record does not report a confidence interval or p-value for the primary endpoint.

How do design assumptions relate to sample size?

The record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also says the target effect can be a stated fraction of the observed effect, and that non-time-to-event estimates are expressed as participants per arm. The numerical planning estimates are not reported in the registry record. Such estimates are illustrations of sample sizes under specified assumptions, not observed outcomes and not a measure of what the completed trial established. The record does not report the trial’s own sample-size justification, the assumptions used in its original planning, or whether its design targeted a particular effect size or power.

Why can dispersion matter?

In general, greater variability among participant outcomes makes an average treatment contrast less precise when other design features are held constant. If outcome variability is not well represented by the chosen statistical model, standard errors and resulting uncertainty estimates may also be unreliable. Over-dispersion is a concern when the observed variation is greater than a model assumes; it can lead to confidence intervals that are too narrow if the model does not account for it. This general issue is relevant to statistical interpretation, but the registry record does not report model diagnostics, distributional checks, or enough primary-outcome results to assess variability in this trial.

The record identifies an observed continuous endpoint and a defined analysis population, but not the full statistical analysis plan. The model used for the primary contrast, any baseline adjustment, rules for excluding observations, and methods for missing outcomes are not reported in the registry record. Therefore, the intended summaries can be explained, but the exact analysis cannot be reconstructed from the recorded information.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures. When a study evaluates multiple outcomes, time points, subscales, or comparisons, multiplicity can arise: the more statistical tests considered, the greater the chance of finding an apparently notable result by chance if each test is treated independently. In general, a prespecified outcome hierarchy or an adjustment method can help control how results are interpreted. The registry record does not report a multiplicity strategy, outcome hierarchy, or whether any adjustment was planned. It also does not provide results across the other outcomes, so their relationship to the primary measure cannot be assessed.

The primary outcome description identifies an ITT Population as randomized participants who received at least one dose of study drugs. The record does not give the number of participants in that population, the number with an observed HAMA result at 8 Weeks, or the number included in any primary analysis. It does not report how missing measurements were handled, whether any imputation was used, or whether analyses based on other populations were conducted. The ITT label should therefore be read with the specific definition in the record, rather than assumed to mean that every randomized participant contributed an observed endpoint.

Missing outcome data can affect interpretation if participants with unavailable measurements differ systematically from those with observed measurements. In general, analysis methods may make assumptions about the reasons data are missing; conclusions can depend on those assumptions. The registry record does not describe missing-data assumptions, sensitivity analyses, or reasons for missing assessments. It also does not report interim analyses or stopping rules. These items are not reported in the registry record, and their absence from the entry does not establish what was done outside the registry.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ecotopic pregnancy (0.9%), acute bronchitis (0.9%).

The registry records one participant with a serious adverse event among 115 at risk in the rufinamide group and one among 114 at risk in the placebo group. It records zero deaths in each group. These are counts of affected participants, not a complete description of the timing, duration, severity, or clinical course of events. The record does not report an inferential comparison of serious adverse-event rates.

For other adverse events, the record lists 75 affected participants among 115 at risk in the rufinamide group and 72 among 114 at risk in the placebo group. The figures describe participants affected, not necessarily the total number of event occurrences; one participant may experience more than one event. The record does not provide enough detail to characterize event duration, severity, attribution, or treatment discontinuation.

The listed top serious-event terms are “Ecotopic Pregnancy” and “Acute Bronchitis,” each shown as 0.9%. The registry entry does not provide further context for those terms in the safety summary. These descriptive entries should not be treated as a complete safety profile or as a precise comparison between groups. In general, uncommon serious events are difficult to characterize from small counts, and the registry record does not give uncertainty intervals for these figures.

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

The record establishes that a randomized, parallel-group Phase 2 exploratory study compared rufinamide with placebo in people with moderate to severe GAD, and that HAMA total-score change from baseline at 8 Weeks was the primary endpoint. It also records the intervention schedule, the placebo description, and an ITT Population definition. These details identify the question the study was designed to examine.

They do not establish the answer. Numerical primary-outcome results are not reported in the registry record, so the observed direction and magnitude of the between-group contrast are unknown from this entry. No confidence interval or p-value is reported for the primary outcome. Without those estimates and the number of participants contributing endpoint data, the precision of the comparison cannot be assessed.

The completed status does not itself show that an outcome favored either group. Similarly, enrollment of 239 is not a measure of treatment effect, and the safety counts do not substitute for the anxiety-score comparison. The registry’s designation of the study as exploratory describes its stated purpose but does not supply evidence about the primary endpoint or explain the statistical criteria used to interpret it.

In general, a trial result is most informative when the estimated contrast, its uncertainty, the analysis population, and the handling of missing observations are all clear. The registry record leaves several of these elements unreported. Accordingly, the evidence in this record supports a description of the trial’s design and its planned primary measure, but not a conclusion about whether the groups differed in HAMA change, how large any difference was, or how precisely it was estimated. These limitations concern the information available in the registry entry; they should not be read as proof that no other analyses or reports exist.

13. Why This Trial Matters Statistically

This trial is statistically notable as a randomized comparison with a clearly identified continuous primary endpoint, a named assessment instrument, a stated timeframe, and a defined population for the primary outcome. Those features make the intended comparison understandable: mean change in HAMA total score at 8 Weeks between participants assigned to rufinamide and those assigned to placebo.

At the same time, the case illustrates why design information and results information are distinct. Randomization and a prespecified measure can support a useful comparison, but readers also need the observed group results, the estimated contrast, and an account of uncertainty. The registry record contains the endpoint description and design labels but no numerical primary-outcome results. As a result, the central statistical question cannot be answered from the recorded results.

Enrollment and outcome availability also answer different questions. The registry lists 239 enrolled, but does not report the endpoint-specific counts or explain how missing outcome measurements were handled. Without those details, readers cannot tell how much information contributed to the primary analysis or judge whether incomplete measurements might affect interpretation.

The record’s six outcome measures make multiplicity an important general consideration, yet no strategy for handling multiple outcomes is reported. The primary contrast also lacks reported uncertainty estimates. Together, these omissions limit the ability to distinguish a potentially meaningful effect from random variation or to evaluate the robustness of the analysis. The lesson is not that the intervention had a particular effect, but that an interpretable trial record requires both a transparent design and accessible outcome estimates with enough statistical context to understand their precision.

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 principal trial-specific limitation in the registry record is that it does not report numerical results for the primary endpoint, despite naming HAMA total-score change at 8 Weeks as the primary outcome. Group-level means and standard deviations, the between-group estimate, and uncertainty measures are not reported. The entry therefore does not support a quantitative interpretation of the principal comparison.

The registry lists overall enrollment of 239 but does not state how many participants were included in the primary analysis or had an observed HAMA result at the specified timeframe. Although the endpoint description defines the ITT Population, it does not report its size or how missing observations were handled. The effect of incomplete outcome data cannot be assessed from the record.

There are six outcome measures and zero analysis records. The registry does not report how multiple outcomes were prioritized or whether any adjustment was planned. The analysis model, baseline adjustment, and sensitivity analyses are also not reported in the registry record. No sample-size justification for the trial is reported; the record’s planning assumptions do not include numerical participant estimates.

The masking descriptions differ: the official title says double-blind, while the registry entry lists triple masking. No explanation of that difference is reported. The record also lacks details about randomization procedures, allocation concealment, site count, adherence, and participant flow. These limitations do not establish that the procedures were absent; they indicate that they are not reported in the registry record. Safety counts are available, but detailed event context and uncertainty estimates are not.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Exploratory Study to Evaluate the Effect of SYN111 (Rufinamide) in Patients With Generalized Anxiety Disorder (GAD) — NCT00595231.
• Registry record last updated 2019-02-27; status last verified 2019-02.
• Results first posted 2019-01-23.
• 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

The registry record identifies NCT00595231 as a completed Phase 2 exploratory randomized, parallel-group study of rufinamide versus placebo for generalized anxiety disorder. It lists 239 participants enrolled and describes a rufinamide schedule of 500 mg for 1 week followed by 1000 mg for 7 weeks, compared with placebo tablets listed as 0 mg.

The primary endpoint is change from baseline in HAMA total score at 8 Weeks, summarized as a mean and standard deviation in an ITT Population defined as randomized participants who received at least one dose. The registry lists six outcome measures but no analysis records and does not report numerical primary-outcome results. Serious adverse events affected one participant in each group; deaths were recorded as zero in each group. The principal limitation for interpreting efficacy is the absence of the primary comparison and its precision estimates in the registry record.