This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia (NCT01556763), a randomized phase 1 study. The primary outcome is Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01556763 |
| Phase | Phase 1 |
| Condition | Schizophrenia, Schizoaffective Disorder, Central Nervous System Diseases |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 21 |
| Arms in the primary outcome | n/a |
| Lead sponsor | FORUM Pharmaceuticals Inc |
| Results posted | Yes |
2. Clinical Question
Population
Participants with schizophrenia receiving stable monotherapy with selected antipsychotics were the intended population. The primary safety population was all randomized patients who ingested at least one dose of study drug or placebo. The registry record also lists schizoaffective disorder and central nervous system diseases among the conditions.
Intervention
EVP-6124 was given alongside the participant’s antipsychotic therapy. The study included a 0.3 mg/day dose and a 1.0 mg/day dose. Each dose was administered as one capsule per day for 21 days.
Comparator
The comparator was matching placebo, administered as one capsule per day for 21 days, alongside antipsychotic therapy. The record describes a randomized, double-blind, placebo-controlled study.
Primary question
The primary question concerned the number of participants experiencing serious and non-serious adverse events, whether spontaneously reported by participants or observed by investigators. Safety and tolerability were also assessed through clinical examinations, vital signs, ECG, continuous cardiac monitoring, and laboratory tests. The study summary says it was designed to provide preliminary evidence about safety, tolerability, pharmacokinetics, and cognitive function. The registry record does not report primary endpoint results as a single treatment comparison.
3. Trial Design
This was a randomized, parallel-group, phase 1 study with triple masking. Its official title describes a double-blind, placebo-controlled randomized study in participants with schizophrenia receiving stable monotherapy with selected antipsychotics. The record lists FORUM Pharmaceuticals Inc as the sponsor and gives the status as completed.
Enrollment was 21. The study began in 2008-04, with primary completion in 2008-08. Participants received EVP-6124 at 0.3 mg/day, EVP-6124 at 1.0 mg/day, or matching placebo, alongside antipsychotic therapy. Each study capsule was taken once per day for 21 days. The adverse-event record lists 4 participants at risk in the placebo group, 9 in the 1.0 mg/day group, and 8 in the 0.3 mg/day group. Those group counts sum to the reported enrollment.
The study summary describes an assessment of safety, tolerability, pharmacokinetics, and effects on cognitive function. Listed secondary outcomes include N100 Gating Ratio, P50 Amplitude Difference, MMN Summed Amplitude, and P300 Peak Amplitude. The registry record lists 13 outcome measures and 4 analyses, but does not report enough detail to reconstruct the allocation procedure, masking roles, or analysis methods for each outcome. Further protocol details 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.
Overall Study
| Stage | Placebo | EVP-6124 (1.0 mg/Day) | EVP-6124 (0.3 mg/Day) |
|---|---|---|---|
| STARTED | 4 | 9 | 8 |
| COMPLETED | 4 | 8 | 8 |
| NOT COMPLETED | 0 | 1 | 0 |
Reasons for not completing this period:
| Reason | Placebo | EVP-6124 (1.0 mg/Day) | EVP-6124 (0.3 mg/Day) |
|---|---|---|---|
| Withdrawal by Subject | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All randomized patients who ingested at least one dose of study drug 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.
| Characteristic | Unit | Placebo | EVP-6124 (1.0 mg/Day) | EVP-6124 (0.3 mg/Day) | Total |
|---|---|---|---|---|---|
| Participants analysed | 4 | 9 | 8 | 21 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 | 9 | 8 | 21 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age Continuous | years | 40.0 (SD 11.6) | 43.1 (SD 11.0) | 51.4 (SD 6.9) | 45.7 (SD 10.4) |
| Sex: Female, Male: Female | Participants | 0 | 3 | 3 | 6 |
| Sex: Female, Male: Male | Participants | 4 | 6 | 5 | 15 |
| Region of Enrollment: United States | participants | 4 | 9 | 8 | 21 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator., measured over Screening (Day -5 for continuous cardiac monitoring) to Day 22.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the number of participants with serious and non-serious adverse events spontaneously reported by participants and/or observed by investigators. Its timeframe ran from screening, including Day -5 for continuous cardiac monitoring, to Day 22. The population was all randomized patients who ingested at least one dose of study drug or placebo.
Counting participants with events is a way to describe how many people experienced a safety event during the specified observation period. It is distinct from counting the total number of events: a participant may experience more than one event, but a participant count records whether each person experienced an event. The registry’s endpoint wording combines serious and non-serious events, while the adverse-event record separately presents serious-event and other-event counts by group.
Safety assessment also included repeated clinical evaluation of physical examinations, vital signs, 12-lead ECG, 24-hour continuous cardiac monitoring, and laboratory tests covering hematology, blood chemistry, and urinalysis. These measures complement event reports by monitoring clinical and laboratory findings during the study. The registry record does not report the primary endpoint as a single numerical result or provide a single estimate comparing EVP-6124 with placebo. It therefore does not support a complete quantitative assessment of the primary endpoint from the registry record alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The adverse-event record reports serious adverse events for 0 of 4 participants in the placebo group, 0 of 9 in the EVP-6124 1.0 mg/day group, and 1 of 8 in the EVP-6124 0.3 mg/day group. For other adverse events, the corresponding counts are 0 of 4, 5 of 9, and 5 of 8. These are descriptive counts within the recorded groups, not estimates adjusted for other factors.
The observed numbers are small, particularly in the placebo group. With few participants, a count can change substantially in relative terms if a single event is added or removed, and the data provide limited precision for comparing groups. No confidence intervals, hypothesis tests, or effect estimates for these event counts are reported in the registry record. As a result, the counts should be read as a description of what was recorded during this study, not as a precise estimate of comparative risk.
The serious-event record lists psychiatric symptom among the top serious terms at 12.5%. The registry record does not give enough detail in the posted results to connect that term to a complete event-level narrative or to establish its relationship to treatment. Death counts are not reported in the registry record; a missing death count should not be interpreted as a reported count of zero.
The primary endpoint combines serious and non-serious adverse events, but the registry record does not provide a single combined primary result. It identifies the primary outcome as having several categories or time points and does not reduce it to one comparison. The separate counts for serious and other adverse events provide partial descriptive information, but do not substitute for the full primary endpoint presentation.
Although the study was designed to assess pharmacokinetics and cognitive function as well as safety and tolerability, numerical results for those outcomes are not reported in the registry record presented. Thus, the posted adverse-event counts are the main interpretable quantitative results in this record. They do not establish a treatment effect, and the absence of a recorded event in a small group does not establish that such events cannot occur.
9. Statistical Methods Explained
Randomization assigns participants to treatment groups by chance, helping limit systematic differences between groups at the outset. This study is identified as randomized and parallel-group: participants were assigned to a group and the groups received their assigned regimens during the study. The registry record does not report the randomization sequence, allocation concealment procedures, or group-specific baseline characteristics, so those aspects cannot be assessed from the record.
What masking contributes
Masking is intended to reduce the influence of knowledge about treatment assignment on participant reports, investigator observations, or assessment. The record labels the study triple-masked and its official title calls it double-blind. It does not specify which participant, investigator, or other roles were masked, or how masking was maintained. The wording alone cannot establish whether masking remained intact throughout the study.
How to read participant counts
The adverse-event data are counts of participants with an event and counts of participants at risk in each treatment group. A participant count answers whether a person had at least one event of the relevant type during the recorded period; it is not the total number of events. The serious-event counts and the other-event counts are presented separately. The primary endpoint wording, by contrast, combines serious and non-serious events. Since a single combined primary outcome result is not reported, the separate group counts cannot fully reproduce that endpoint.
Precision and uncertainty
A confidence interval is a range of values compatible with the data under a specified statistical method. It communicates uncertainty around an estimate; a wider interval indicates less precision. No confidence intervals for the adverse-event comparisons are reported in the registry record. With modest group counts, the observed counts alone cannot show how precisely a group difference has been estimated. The registry record also does not report a formal test or a model-based estimate for these safety data.
For event counts, statistical methods may need to account for the fact that events can vary more than a simple model expects. This is called over-dispersion: the observed variability exceeds the model’s assumed variability. It can lead a basic model to understate uncertainty if it is ignored. This is a general statistical consideration, not a claim that over-dispersion occurred or that a particular count model was used in this study. The analysis methods for the adverse-event results are not reported in the registry record.
Planning calculations are not trial results
Planning illustrations based on an observed effect are not the same as observed power and are not evidence that the original study was designed around that effect. The record describes illustrative assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it says the effect to detect is a stated fraction of the observed effect. These assumptions describe a planning exercise, not the trial’s own design rationale. The protocol’s sample-size justification is not reported in the registry record. No planning sample-size values are described in the registry record information used for this interpretation.
What the design can support
General statistical interpretation distinguishes descriptive results from inferential claims. Descriptive counts state what was observed in the recorded groups. Inferential analyses use statistical methods to quantify uncertainty and assess how results may generalize beyond those participants. Here, the posted adverse-event counts are descriptive, and no accompanying confidence intervals or treatment-comparison test are reported. The registry record does not report an interim-analysis plan, a prespecified model, or detailed handling of repeated outcomes. These omissions limit reconstruction of the analysis, but do not imply that any particular method was or was not used outside the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 13 outcome measures and 4 analyses, including safety measures and cognitive or electrophysiological outcomes. When a study assesses multiple outcomes or comparisons, the chance of at least one apparently notable result can increase if each is tested separately. Statistical approaches to multiplicity can adjust interpretation or control error across a family of tests. The registry record does not report a multiplicity strategy, identify a family of confirmatory comparisons, or describe whether the listed analyses were exploratory or confirmatory. No adjustment should therefore be assumed.
The record does not report a complete statistical analysis plan, including prespecified handling of missing outcome data, withdrawals, or unavailable measurements. It identifies the primary safety population as all randomized patients who ingested at least one dose of study drug or placebo. That definition does not establish how missing observations were handled within that population, or whether another population was used for other outcomes.
The registry record does not report the number of missing observations for each outcome, reasons for missingness, or sensitivity analyses. Missing-data methods matter because conclusions can depend on whether unavailable observations are related to participant health, treatment, or other measured information. Without these details, the extent to which missingness could affect estimates cannot be assessed. The results should be interpreted as the data recorded in the registry, with the analysis-population and missing-data details that are not reported in the registry record left unresolved.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo | 0 | 4 | 0.0% |
| EVP-6124 (1.0 mg/Day) | 0 | 9 | 0.0% |
| EVP-6124 (0.3 mg/Day) | 1 | 8 | 12.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 0 of 4 |
| EVP-6124 (1.0 mg/Day) | 5 of 9 |
| EVP-6124 (0.3 mg/Day) | 5 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | EVP-6124 (1.0 mg/Day) | EVP-6124 (0.3 mg/Day) |
|---|---|---|---|---|
| Psychiatric symptom | Psychiatric disorders | 0 of 4 | 0 of 9 | 1 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | EVP-6124 (1.0 mg/Day) | EVP-6124 (0.3 mg/Day) |
|---|---|---|---|---|
| Skin irritation | Skin and subcutaneous tissue disorders | 0 of 4 | 5 of 9 | 5 of 8 |
| Tinea cruris | Infections and infestations | 0 of 4 | 0 of 9 | 1 of 8 |
| Neutrophil count increased | Investigations | 0 of 4 | 1 of 9 | 0 of 8 |
| White blood cell count increased | Investigations | 0 of 4 | 1 of 9 | 0 of 8 |
| Psychiatric symptom | Psychiatric disorders | 0 of 4 | 0 of 9 | 1 of 8 |
| Skin erosion | Skin and subcutaneous tissue disorders | 0 of 4 | 0 of 9 | 1 of 8 |
Serious events with the highest arm-level rate: psychiatric symptom (12.5%).
The serious adverse-event counts are 0 of 4 participants for placebo, 0 of 9 for EVP-6124 1.0 mg/day, and 1 of 8 for EVP-6124 0.3 mg/day. The record separately reports other adverse events for 0 of 4, 5 of 9, and 5 of 8 participants, respectively. The terms “serious” and “other” describe separate categories in the adverse-event results; the latter should not be treated as a synonym for harmless or unimportant.
These counts refer to participants with events, not total event episodes. They describe what was recorded in each small group during the study and do not establish that the groups had the same or different underlying event rates. The registry record does not provide uncertainty intervals or a formal comparison for these figures. It lists psychiatric symptom at 12.5% among the top serious terms, but does not provide a fuller event-level account in the posted results. Death counts are not reported in the registry record, so no conclusion about deaths can be drawn from that blank information.
12. What the Result Does, and Does Not, Mean
This phase 1 randomized study was designed to examine EVP-6124 at 0.3 mg/day and 1.0 mg/day, each alongside antipsychotic therapy, compared with placebo alongside antipsychotic therapy. The registry record reports group-level adverse-event counts, including one participant with a serious adverse event in the 0.3 mg/day group and none recorded in the other groups. It also reports other adverse events in the two EVP-6124 groups and none in the placebo group. Those observations are descriptive and come from groups with limited participant counts.
The posted information does not establish whether any apparent differences are due to treatment rather than chance or other factors. No comparative estimate, confidence interval, or formal test for these counts is reported. A zero count in a group does not prove that the event cannot occur, just as an event recorded in a treatment group does not by itself establish that treatment caused it.
The study summary also names pharmacokinetics and cognitive function as aims, and the record lists several cognitive or electrophysiological outcomes. Numerical results for those outcomes are not reported in the registry record. The primary safety endpoint is described, but a single combined primary result is not given. Consequently, the adverse-event counts do not answer every question the study was designed to address.
These registry results are bounded by the study’s recorded population, regimens, and observation period. They should not be read as a broad estimate for other populations or treatment settings. The record supports a description of events reported or observed during this study; it does not, on its own, establish a clinical benefit or a definitive safety profile.
13. Why This Trial Matters Statistically
Small randomized studies can be useful for early characterization of a treatment regimen, but their results require careful attention to uncertainty. This trial’s enrollment was 21, with group counts of 4, 9, and 8 in the adverse-event record. Such counts can describe what happened among enrolled participants, while offering limited precision for comparing less common events across groups.
The study illustrates why endpoint definitions and reported analyses matter. Its primary endpoint concerns participants with serious and non-serious adverse events, whereas the posted adverse-event results separate serious events from other events. Since the registry record does not provide a single combined primary result, readers should distinguish the endpoint definition from the partial descriptive results that are available.
It also illustrates the difference between a study aim and a posted numerical result. The summary describes safety, tolerability, pharmacokinetics, and cognitive function, but the numerical information reported in the record does not cover all of those aims. Outcome names alone do not establish the size, direction, or precision of a result.
Finally, planning illustrations based on observed effects should not be confused with the trial’s original design justification or with evidence of adequate power. The record gives illustrative assumptions but does not report the protocol’s sample-size rationale. Taken together, these features make transparent endpoint reporting, analysis details, and uncertainty essential to interpreting early clinical evidence.
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 on the methods used to analyze adverse events. It does not report confidence intervals, hypothesis tests, adjusted estimates, or the statistical model used for the posted counts. The primary endpoint combines serious and non-serious events, but its results are not reduced to a single comparison in the record. This makes it difficult to assess the primary outcome as defined.
The group sizes are small, and the placebo group includes 4 participants in the adverse-event record. Counts from groups of this size provide limited information about uncommon events and comparative precision. The record does not give a full account of event timing, duration, severity beyond the serious-event distinction, or how recurrent events were summarized.
Although the record identifies a population for the primary safety endpoint, it does not report detailed analysis-population rules for the other outcomes. Missing-data amounts, reasons, and methods are also not reported. The registry does not specify the roles covered by triple masking or provide enough information to assess the randomization process.
The study summary describes pharmacokinetic and cognitive aims, but numerical results for these outcomes are not reported in the registry record. Death counts are not reported either. These absences limit the scope of conclusions that can be drawn from the posted information; they should not be filled in by assumptions. The protocol, sample-size justification, interim analyses, and detailed statistical plan are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia — NCT01556763.
- Registry record last updated 2012-06-21; status last verified 2012-05.
- Results first posted 2012-06-21.
- 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.
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18. Record Summary
NCT01556763 is a completed randomized, parallel-group, phase 1 study of EVP-6124 in participants with schizophrenia receiving stable antipsychotic therapy. The study compared 0.3 mg/day and 1.0 mg/day EVP-6124 with matching placebo. Each capsule regimen was administered daily for 21 days. Enrollment was 21, and the record identifies the study as triple-masked.
The primary endpoint concerned participants with serious and non-serious adverse events during the period from screening to Day 22. The adverse-event record reports serious-event counts of 0 of 4 for placebo, 0 of 9 for 1.0 mg/day, and 1 of 8 for 0.3 mg/day; other-event counts were 0 of 4, 5 of 9, and 5 of 8. The registry record does not report one combined primary result or uncertainty estimates for these counts. Numerical results for the listed pharmacokinetic and cognitive outcomes are not reported in the registry record.