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 Multicenter, Open-label, Safety and Tolerability Study (NCT01649557), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events (AEs) During First 6 Weeks..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01649557 |
| Phase | Phase 2 |
| Condition | Schizophrenia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 244 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Otsuka Pharmaceutical Development & Commercialization, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Adults with schizophrenia who had completed participation in Study 331-07-203 and whom investigators judged could benefit from continued treatment with oral OPC-34712. The safety population is described as participants who received at least one dose and were enrolled in the 6-week study.
Intervention
Open-label oral OPC-34712 as monotherapy. The study summary describes doses from 1 to 6 mg and an intended 52-week study duration.
Comparator
There was no randomized control group. The registry record lists prior Brexpiprazole, prior Placebo, and prior Aripiprazole groups in its safety information; these are prior-treatment categories, not like-for-like randomized treatment arms.
Primary question
How many participants experienced adverse events during the first 6 weeks? The registry defines adverse events broadly, including new medical problems and worsening of existing problems, whether or not investigators considered them related to study medication.
The study is framed as an assessment of safety and tolerability during continued treatment, not as a randomized test of OPC-34712 against another treatment. Its open-label, single-group design means that the main question is descriptive: what adverse events were recorded among participants receiving the study medication? The listed prior-treatment categories may help describe who entered the study, but they do not establish a causal comparison between treatments.
The registry also lists clinical measures as secondary outcomes, including changes in PANSS, CGI-S, and PSP scores, as well as CGI-I, positive response, and discontinuation due to lack of efficacy. Their presence indicates that clinical status was tracked, but outcome values and analyses for those measures are not reported in the registry record. The record therefore supports a description of the study question and its safety focus, but not a conclusion about comparative efficacy or whether treatment caused any particular event.
3. Trial Design
This was a Phase 2, multicenter, open-label study with a single-group model and no allocation to randomized treatment arms. It was listed as completed, with enrollment of 244 participants. The study summary describes outpatient monotherapy with oral OPC-34712 at 1 to 6 mg over 52 weeks. Participants were to be drawn from people who had completed Study 331-07-203 and whom the investigator judged could benefit from continued treatment.
The lack of masking means that participants and investigators were not blinded to study treatment. The absence of a concurrent randomized comparator is central to interpreting the results: events can be counted and described, but a difference attributable to the medication cannot be separated from background illness, other influences, or the expectations associated with open-label care using this design alone.
There is a timing distinction in the registry record. The study summary describes a 52-week study, while the primary outcome is defined as the number of participants with adverse events from baseline up to 6 weeks, and the safety-population description refers to participants enrolled in the 6-week study. The registry record does not explain this difference. These descriptions should therefore be kept distinct rather than treated as interchangeable.
The safety information is divided by prior treatment: Prior Brexpiprazole, Prior Placebo, and Prior Aripiprazole. Those labels describe participant groups in the posted safety data, not randomized arms within this study. The record does not report how participants were assigned to these categories or provide a like-for-like comparison plan. It also does not report a sample-size justification or a detailed statistical analysis plan.
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: Trial consisted of a screening visit, treatment phase and safety follow-up at 30 (± 2) days after the last dose of medication. Eligible participants for the trial were those who completed protocol NCT00905307 and who in the investigators judgment would benefit from the treatment.
Overall Study
| Stage | Prior Brexpiprazole | Prior Placebo | Prior Aripiprazole |
|---|---|---|---|
| STARTED | 179 | 41 | 24 |
| 6-week Enrollers | 159 | 35 | 22 |
| 52-week Enrollers | 20 | 6 | 2 |
| COMPLETED | 135 | 27 | 15 |
| NOT COMPLETED | 44 | 14 | 9 |
Reasons for not completing this period:
| Reason | Prior Brexpiprazole | Prior Placebo | Prior Aripiprazole |
|---|---|---|---|
| Lost to Follow-up | 5 | 0 | 3 |
| Adverse Event | 7 | 5 | 1 |
| Met withdrawal criteria | 4 | 0 | 0 |
| Physician Decision | 8 | 2 | 1 |
| Withdrawal by Subject | 15 | 5 | 4 |
| Protocol deviation | 0 | 2 | 0 |
| Lack of Efficacy | 5 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole and were enrolled in the 6-week study.
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 | Prior Brexiprazole | Prior Placebo | Prior Apripiprazole | Total |
|---|---|---|---|---|---|
| Participants analysed | 179 | 41 | 24 | 244 | |
| Age, Continuous | Years | 39.1 (SD 10.1) | 41.4 (SD 11.2) | 41.2 (SD 12) | 39.7 (SD 10.5) |
| Sex: Female, Male: Female | Participants | 69 | 17 | 5 | 91 |
| Sex: Female, Male: Male | Participants | 110 | 24 | 19 | 153 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AEs) During First 6 Weeks., measured over From Baseline up to 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with adverse events during the first 6 weeks, from baseline up to 6 weeks. It is a count of participants, rather than a measurement of symptom change or an event rate over person-time. The registry defines an adverse event as a new medical problem or worsening of an existing problem while a participant is enrolled, regardless of whether the investigator considered it related to study medication.
The record distinguishes treatment-emergent adverse events from the broader adverse-event definition. A treatment-emergent event is described as one starting after study medication begins, or an event present at baseline that worsens or meets specified seriousness, relatedness, or medication-action criteria. A serious adverse event is defined by outcomes such as death, life-threatening occurrence, or inpatient hospitalization or prolonged hospitalization.
Counting affected participants is a useful way to describe how many people had recorded events during a defined observation period. It does not convey the event's severity, duration, recurrence, or causal relationship unless those details are reported separately. For this endpoint, the registry record does not report a single overall numerical count. The posted safety figures instead provide serious and other adverse-event counts within prior-treatment groups, so they should not be mistaken for a complete overall result for the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety information gives counts for serious and other adverse events in three groups defined by prior treatment. In the Prior Brexpiprazole group, 4 of 178 participants were listed as affected by serious adverse events, and 31 of 178 by other adverse events. In the Prior Placebo group, the corresponding counts are 6 of 41 and 10 of 41. In the Prior Aripiprazole group, they are 1 of 23 and 4 of 23. These are descriptive counts, not results from randomized comparisons.
The listed serious-event terms are Schizophrenia at 7.3%, Psychotic disorder at 4.3%, Bronchitis at 2.4%, Influenza at 2.4%, and Convulsion at 2.4%. The registry record does not supply enough context in these figures to interpret them as treatment-caused events. An adverse event is recorded whether or not the investigator considered it drug related, and the study has no concurrent randomized control group for estimating how event occurrence would differ under another treatment.
The group counts should be read as observations among the participants represented in each prior-treatment category. Differences in the displayed counts cannot establish that one category had greater or lesser risk: the group sizes differ, the categories are based on prior treatment, and the record does not describe random assignment to them. The counts also do not provide uncertainty intervals or adjusted comparisons. No inferential analysis is listed in the registry record.
The stated primary endpoint concerns adverse events during the first 6 weeks, while the study summary describes a 52-week study. The registry safety dataset is described as including participants who received at least one dose and were enrolled in the 6-week study. The record does not reconcile these descriptions or specify whether the safety counts represent only that early period or a different reporting window. They should therefore be interpreted within the definitions attached to the safety data rather than assumed to summarize the full 52-week period.
The clinical outcomes listed as secondary measures include PANSS, CGI-S, PSP, CGI-I, response, and discontinuation due to lack of efficacy. Their results are not reported in the registry record. Consequently, the available figures support a limited descriptive reading of the posted safety data, but not a conclusion about comparative safety, efficacy, or the overall balance of benefits and harms.
9. Statistical Methods Explained
The design determines what kinds of statistical conclusions are supportable. This study is listed as single-group, open-label, and without allocation to randomized arms. In general, randomization helps make treatment groups comparable by distributing measured and unmeasured characteristics across groups. Without that feature and without a concurrent control group, observed events can be described, but a contrast cannot isolate the effect of study treatment from other possible explanations.
What does a participant count represent?
The primary outcome is expressed as the number of participants with adverse events, with participants as the unit. A participant count answers how many people had at least one event under the registry definition; it is not necessarily the number of event episodes. One participant may have more than one event, so participant counts and event counts are different quantities. The registry does not report an overall primary-endpoint count alongside the posted group-level serious and other adverse-event counts.
In general, a proportion can put a count in relation to the number of participants observed, but the numerator and denominator must refer to a clearly defined population and period. The safety figures provide counts and numbers at risk for each prior-treatment category. They do not, by themselves, establish that the categories are comparable. Nor do they indicate whether each person was observed for the same duration. The record does not report person-time or a rate analysis.
Why does the study design matter?
Open-label treatment means that treatment knowledge is not masked from participants and investigators. This can matter for outcomes that depend on reporting, clinical judgment, or decisions about hospitalization and medication changes. The study's adverse-event definitions include events whether or not investigators judged them related to treatment, which is a broad surveillance approach. It does not eliminate the possibility that event identification or attribution could be influenced by the open-label design.
In general, a confidence interval describes the range of effect estimates compatible with the data and a specified statistical procedure. It conveys precision as well as the estimate itself; a point estimate alone does not show how uncertain it is. No confidence intervals for the adverse-event counts or comparisons are reported in the registry record. The posted counts therefore offer no interval-based estimate of precision.
What can group comparisons show?
The three safety groups are titled by prior treatment. They are not described as randomized arms in this study, and the record explicitly indicates that the trial is not a randomized comparison. A raw comparison between such groups may reflect differences in participant history, selection, follow-up, or other factors, in addition to any treatment-related influence. Statistical adjustment could address some measured differences in a suitable analysis, but no adjusted analysis is reported. It would not be appropriate to interpret the displayed group counts as proof of a treatment effect.
For general context, over-dispersion occurs when outcome variability is greater than a statistical model expects. It can make standard errors and inferential conclusions unreliable if the model does not account for the extra variation. The registry record does not report a model for these event counts, an over-dispersion assessment, or a related correction. This concept is therefore relevant as a general consideration, not as a documented feature of the posted analysis.
How should planning calculations be read?
General sample-size calculations can illustrate the number of participants per arm for a chosen power and assumed effect under stated statistical assumptions. They are planning illustrations, not observed power and not evidence that a trial was adequately powered. The registry record gives assumptions for illustrations based on a stated fraction of an observed effect, equal allocation, a two-sided significance level of 0.05, and a normal approximation. No resulting sample-size figures are reported in the registry record for this record, and the trial itself was a single-group study rather than an equal-allocation randomized comparison. The record does not report the trial's own sample-size justification.
Statistical interpretation also depends on prespecification: which outcomes, time points, populations, and analyses were planned before results were known. The registry lists 10 outcome measures and no analyses. A detailed statistical plan, including model choice, handling of repeated measures, uncertainty estimation, or adjustments for multiple outcomes, is not reported in the registry record. Without those details, the posted descriptions cannot establish how the listed outcomes were analyzed or whether the reported safety summaries were prespecified.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 10 outcome measures, including the primary adverse-event endpoint and secondary clinical measures. Considering many outcomes can create multiplicity: when several statistical tests are conducted, the chance of at least one apparently notable result can increase. General approaches include prespecifying a hierarchy of outcomes or adjusting inference across tests. The registry record does not report whether any such approach was planned or used. It lists no analyses, and results for the secondary outcomes are not reported in the registry record.
Missing data can affect estimates when participants do not complete follow-up or when outcome measurements are unavailable. Appropriate handling depends on the amount, timing, and reasons for missingness, as well as the outcome and analysis. The record does not report missing-data counts, reasons for missingness, imputation methods, sensitivity analyses, or how participants with incomplete observations were handled. No assumptions about these procedures can be made from the endpoint descriptions alone.
The record describes a safety population as participants who received at least one dose and were enrolled in the 6-week study. It does not report a separate analysis population for the secondary clinical outcomes, nor does it clarify whether all enrolled participants contributed to each outcome. The relation between the 52-week study description and the 6-week safety endpoint is also not explained. These omissions limit interpretation of both the observation period and the population represented by each result.
For general context, intention-to-treat and safety populations answer different questions: an intention-to-treat population generally follows assigned treatment groups, while a safety population commonly includes participants who received treatment. This study is not listed as randomized, and the record does not describe an intention-to-treat analysis. The safety-population description is available, but further analysis-population details are not reported in the registry record.
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 |
|---|---|---|---|
| Prior Brexpiprazole | 4 | 178 | 2.2% |
| Prior Placebo | 6 | 41 | 14.6% |
| Prior Aripiprazole | 1 | 23 | 4.3% |
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 |
|---|---|
| Prior Brexpiprazole | 31 of 178 |
| Prior Placebo | 10 of 41 |
| Prior Aripiprazole | 4 of 23 |
Most frequent serious adverse event terms
| Event term | Organ system | Prior Brexpiprazole | Prior Placebo | Prior Aripiprazole |
|---|---|---|---|---|
| Schizophrenia | Psychiatric disorders | 2 of 178 | 3 of 41 | 0 of 23 |
| Psychotic disorder | Psychiatric disorders | 2 of 178 | 1 of 41 | 1 of 23 |
| Bronchitis | Infections and infestations | 0 of 178 | 1 of 41 | 0 of 23 |
| Influenza | Infections and infestations | 0 of 178 | 1 of 41 | 0 of 23 |
| Convulsion | Nervous system disorders | 0 of 178 | 1 of 41 | 0 of 23 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Prior Brexpiprazole | Prior Placebo | Prior Aripiprazole |
|---|---|---|---|---|
| Insomnia | Psychiatric disorders | 10 of 178 | 3 of 41 | 0 of 23 |
| Headache | Nervous system disorders | 6 of 178 | 5 of 41 | 0 of 23 |
| Tremor | Nervous system disorders | 9 of 178 | 1 of 41 | 0 of 23 |
| Anxiety | Psychiatric disorders | 5 of 178 | 0 of 41 | 2 of 23 |
| Extrapyramidal disorder | Nervous system disorders | 2 of 178 | 1 of 41 | 2 of 23 |
Serious events with the highest arm-level rate: schizophrenia (7.3%), psychotic disorder (4.3%), bronchitis (2.4%), influenza (2.4%), convulsion (2.4%).
The safety figures are organized by prior treatment and distinguish serious adverse events from other adverse events. For Prior Brexpiprazole, the serious-event count is 4 among 178 at risk and the other-event count is 31 among 178. For Prior Placebo, the counts are 6 among 41 and 10 among 41. For Prior Aripiprazole, they are 1 among 23 and 4 among 23. The serious-event terms listed include Schizophrenia at 7.3%, Psychotic disorder at 4.3%, Bronchitis at 2.4%, Influenza at 2.4%, and Convulsion at 2.4%.
These counts do not establish that study medication caused the events. The registry's adverse-event definition includes events regardless of investigator judgment about drug relatedness. The groups are prior-treatment categories, not randomized control groups, and the record does not report adjusted comparisons or uncertainty intervals. Serious and other event counts should not be added or treated as mutually exclusive categories without information about overlap. The record also does not reconcile the first 6-week primary endpoint with the 52-week study description, so the duration represented by these particular safety summaries should not be inferred beyond their stated descriptions.
12. What the Result Does, and Does Not, Mean
The registry record describes an open-label study in which participants received oral OPC-34712 as monotherapy and safety was a central focus. The posted safety information gives serious and other adverse-event counts across groups defined by prior treatment, along with a short list of serious-event terms and percentages. These are useful descriptive observations about the participants included in those categories, but they are not a randomized comparison of treatment strategies.
The counts do not show whether events were caused by the study medication. The record's event definition explicitly includes events that investigators did not consider drug related. The design also lacks a concurrent randomized comparator, so it cannot establish what event occurrence would have been in a similar group receiving another treatment or no study medication. The group labels refer to prior treatment and do not solve that comparison problem.
The figures also do not, on their own, describe the full safety experience over the intended study duration. The brief summary refers to 52 weeks, while the primary endpoint and safety-population description focus on 6 weeks. The registry record does not explain how these timeframes relate to the posted group counts. In addition, the record does not report a single overall numerical result for the primary endpoint, nor does it provide results for the listed secondary clinical outcomes.
Accordingly, the posted information supports a limited account of recorded adverse events, not a conclusion about comparative effectiveness, comparative safety, or a treatment's overall benefit-harm balance. A lack of reported analysis is not evidence that no events occurred or that a treatment has a particular effect. Interpretation is bounded by the definitions, follow-up information, and analyses actually documented in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative because its design illustrates the difference between describing events and estimating comparative effects. A single-group, open-label study can document safety observations during treatment and characterize who experienced recorded events. Without random allocation and a concurrent control group, however, those observations cannot separate the influence of treatment from other explanations.
The prior-treatment categories make the distinction especially important. Their counts may look like a set of groups to compare, but the registry record does not describe them as randomized arms. Their different participant counts and histories mean that a raw contrast would not have the interpretation of a randomized treatment comparison. Clear labels and careful language help prevent descriptive safety summaries from being mistaken for causal evidence.
The record also highlights why endpoint timing and population definitions matter. The study summary describes a 52-week study, while the primary endpoint and safety population refer to 6 weeks. This difference affects what follow-up the reader might think the results represent, and it is not reconciled in the registry record. A numerical count is meaningful only alongside a clearly understood population, event definition, and observation period.
Finally, the registry lists a range of clinical measures but does not report their results or analyses. This gap limits conclusions about how the study's safety observations relate to clinical outcomes. Statistically, a study's design and reporting determine the questions it can answer; a precise description of those boundaries is as important as a list of observed counts.
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 primary limitation is the single-group, open-label design with no randomized comparator. It supports description of events observed during treatment but cannot provide a randomized estimate of how event occurrence compares with an alternative. The categories in the safety record are defined by prior treatment and should not be interpreted as study treatment arms.
The record has a timeframe ambiguity: the brief summary describes a 52-week study, while the primary endpoint runs from baseline up to 6 weeks and the safety population is described in relation to a 6-week study. The registry record does not explain this distinction or state how it applies to the displayed safety counts. As a result, the duration represented by those figures is not clear from the record.
The registry record does not report a single overall count for the primary endpoint, confidence intervals, adjusted comparisons, or a detailed statistical analysis plan. It lists no analyses, and results for the secondary clinical outcomes are not reported in the registry record. Missing-data methods, outcome-specific analysis populations, and the handling of multiple outcomes are also not reported.
Finally, the primary endpoint description refers to adverse events, while the numerical safety information is separated into serious and other events by prior-treatment group. The record does not explain whether these categories overlap or how they map to the overall primary endpoint. The intervention is named OPC-34712 in the study description, while the safety-population wording refers to brexpiprazole; the registry record does not explain this naming difference. These limitations constrain how specifically the safety results can be interpreted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Multicenter, Open-label, Safety and Tolerability Study — NCT01649557.
- Registry record last updated 2015-10-29; status last verified 2015-09.
- Results first posted 2015-10-29.
- 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.
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18. Record Summary
This completed Phase 2 study enrolled 244 adults with schizophrenia in a multicenter, open-label, single-group study of oral OPC-34712 monotherapy. The brief summary describes outpatient treatment at 1 to 6 mg over 52 weeks, among eligible participants who had completed Study 331-07-203 and whom investigators judged could benefit from continued treatment.
The primary endpoint is the number of participants with adverse events from baseline up to 6 weeks. The registry's safety information presents serious and other adverse-event counts within prior Brexpiprazole, prior Placebo, and prior Aripiprazole groups. These are descriptive, nonrandomized categories. The registry record does not report a single overall primary-endpoint result, inferential analyses, or results for the listed secondary outcomes.
The difference between the 52-week summary and the 6-week endpoint description is not explained in the registry record. The design and reporting support a bounded description of safety observations, not a causal or comparative treatment conclusion.