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 Open-label, Extension Study of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in Patients With Schizophrenia (NCT01683058), a na phase 3 study. The primary outcome is Percentage of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Discontinued Investigational Medicinal Product (IMP) Due to AEs, Serious TEAEs and Outcome of Death.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01683058 |
| Phase | Phase 3 |
| Condition | Schizophrenia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 74 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Otsuka Pharmaceutical Development & Commercialization, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants with schizophrenia who entered the extension after completing Trial 31-12-291, at the investigator’s discretion. The registry record describes the safety population as all enrolled participants who took at least one injection of aripiprazole IM depot during the treatment period.
Intervention
Aripiprazole IM Depot, at 400 mg or 300 mg once monthly (every 28 days) for 24 weeks.
Comparator
There was no separate comparator arm. The trial is described as single-group, with no randomized allocation and no masking.
Primary question
What percentages of participants reported treatment-emergent adverse events, severe treatment-emergent adverse events, serious treatment-emergent adverse events, discontinuation of investigational medicinal product because of adverse events, or death from baseline to Week 24?
This is a safety-focused question about events observed during an open-label extension, not a question about whether aripiprazole is better than another treatment. The registry describes the study as part of the aripiprazole IM depot clinical development program and says that additional safety and tolerability data would be collected. Its brief summary places the extension after a double-blind acute-treatment trial and states that entry into the extension was at the investigator’s discretion.
That context matters for interpretation. Participants who enter an extension are not necessarily representative of everyone with schizophrenia or everyone who might receive the intervention. In this study, eligibility depended on completing the preceding trial and on investigator discretion. The registry record does not report how many people were eligible to enter the extension but did not do so, or why any individual did not enter.
Because the extension has one treatment group, the central descriptive question is which adverse events were recorded among its participants during the specified follow-up. The study does not establish how those event frequencies would compare with another treatment or with no treatment. A single-group design can describe events that occur during exposure, but it cannot by itself separate treatment-related effects from events that might also occur because of the underlying condition, other circumstances, or chance.
3. Trial Design
The registry identifies this as a phase 3, multicenter, open-label extension study in patients with schizophrenia. It is a single-group trial: the listed intervention is aripiprazole IM Depot, allocation is not applicable, and masking is absent. The listed enrollment is 74. The record marks the study as completed, with a start date of 2013-01 and primary completion of 2014-02.
The intervention description specifies aripiprazole IM Depot 400 mg or 300 mg once monthly, every 28 days, for 24 weeks. The official title calls the extension a 26-week study, while the intervention description gives a 24-week treatment duration and the primary endpoint timeframe runs from baseline to Week 24. Those are distinct descriptions in the registry record; the record does not explain the difference between the title duration and the stated treatment and endpoint periods.
The brief summary describes the extension as following Trial 31-12-291. That earlier trial included a 12-week double-blind acute-treatment phase, and participants who completed it could enter this open-label extension at the investigator’s discretion. This is background from the registry summary, not a randomized comparison within the extension itself.
All enrolled participants in the stated safety analysis took at least one injection during the treatment period. The record lists several secondary outcomes, including changes in suicidal ideation intensity, extrapyramidal-symptom scales, body temperature, heart rate, and supine blood pressure. It also lists 25 outcome measures overall. How participants were assigned to the 400 mg or 300 mg dose, whether dose changes were permitted, and the specific analysis methods for these outcomes are not reported in the registry record.
The design therefore supports a descriptive reading of the extension’s safety observations. With no concurrent comparison group, observed event frequencies cannot be interpreted as comparative treatment effects. The registry record does not report a statistical analysis plan, a sample-size justification, or a planned interim-analysis approach.
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: Participants entered this trial after completing the Week 12/Early Termination (ET) visit of trial NCT01663532 as it served as the Baseline evaluations for this trial.
Overall Study
| Stage | Aripiprazole IM Depot 400/300 mg |
|---|---|
| STARTED | 74 |
| COMPLETED | 45 |
| NOT COMPLETED | 29 |
Reasons for not completing this period:
| Reason | Aripiprazole IM Depot 400/300 mg |
|---|---|
| Lost to Follow-up | 9 |
| Adverse Event | 6 |
| Subject Met Withdrawal Criteria | 5 |
| Withdrawal by Subject | 7 |
| Lack of Efficacy | 2 |
Analysis population for the primary outcome, as defined in the registry: In safety analysis, all enrolled participants took at least one injection of aripiprazole IM depot 400/300mg in the IM depot treatment period.
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 | Aripiprazole IM Depot 400/300 mg |
|---|---|---|
| Participants analysed | 74 | |
| Age, Continuous | Years | 43.0 (SD 11.7) |
| Sex: Female, Male: Female | Participants | 18 |
| Sex: Female, Male: Male | Participants | 56 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Discontinued Investigational Medicinal Product (IMP) Due to AEs, Serious TEAEs and Outcome of Death, measured over Baseline to Week 24.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants reporting treatment-emergent adverse events during the period from baseline to Week 24. Its listed event categories are treatment-emergent adverse events (TEAEs), severe TEAEs, serious TEAEs, discontinuation of investigational medicinal product (IMP) because of adverse events, and outcome of death. The registry defines a TEAE as an adverse event that began after the first injection, or was continuous from baseline and was serious, study drug-related, or resulted in death.
A percentage expresses how common an event category was among the participants in the relevant analysis population. Such measures are useful in safety reporting because they describe the proportion of exposed participants for whom an event was recorded over a specified period. The different categories capture different aspects of safety: severity, seriousness, treatment discontinuation, and death are not interchangeable classifications. An event can be relevant to more than one category, so the categories should not be assumed to be mutually exclusive.
The endpoint is descriptive. It does not, by itself, establish that the intervention caused an event. The registry record does not report the precise event-level results for every component of the primary endpoint, nor does it report confidence intervals or a comparative estimate. The safety population is described as all enrolled participants who took at least one injection during the treatment period.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study’s reported safety figures should be read as observations in a single-group extension. The registry lists 5 participants with a serious adverse event among 74 at risk for serious events, and 40 participants with another adverse event among 74 at risk for those events. These are event-category counts, not estimates from a randomized comparison. The record separately lists serious-event terms and their percentages: Depression, 2.7%; Schizophrenia, 2.7%; Abortion spontaneous, 1.4%; and Suicidal ideation, 1.4%.
These figures describe what was recorded in the trial, rather than what would have occurred under a different treatment or without treatment. The open-label, single-group design has no concurrent control arm to help distinguish events associated with the intervention from background events, the underlying condition, or other influences. The registry record also does not report a causal analysis for the listed events.
The primary endpoint covers several categories, including severe and serious TEAEs, discontinuation because of adverse events, and death. The available record does not give a complete set of numerical results for each of these categories. Deaths are recorded as null in the adverse-event data, so a death count is not reported in the registry record. A null entry should not be converted into a zero or treated as confirmation that no deaths occurred.
Precision is also important. A proportion based on a limited study population can be uncertain, particularly for uncommon events. Confidence intervals would help convey the range of values compatible with the observed data, but they are not reported in the registry record. Nor are p-values or adjusted estimates reported for the primary endpoint. Without those quantities, the displayed event counts and percentages should be interpreted as descriptive rather than as evidence of a statistically established difference.
General statistical context: a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. It does not remove the design limitations or show that an event was caused by treatment. For a single-group safety study, uncertainty in a percentage is only one part of interpretation; the absence of a comparator remains important even if a percentage were estimated precisely.
The reported serious-event terms should be understood as the registry’s listed events and percentages, not as a ranking of treatment effects. The record does not explain the event coding process or the criteria used to select the listed terms. It also does not report participant-level overlap across event categories. Counts in different categories therefore should not be added, and the listed percentages should not be interpreted as independent or mutually exclusive risks.
Overall, the registry supports a limited descriptive account of adverse events during the extension. It does not support a conclusion about comparative safety, effectiveness, or causation. The absence of inferential results in the registry record is not evidence that a difference was absent; it means that such a difference is not established by the record.
9. Statistical Methods Explained
What does a percentage measure?
General statistical context: for a binary safety outcome, each participant is classified according to whether the event was recorded during the defined observation period. A percentage describes the share of participants with that event among those considered at risk or included in the relevant analysis. It is a summary of observed frequency, not a direct measure of causation.
For this trial, the primary endpoint specifies percentages of participants with several event categories between baseline and Week 24. The registry states that the safety analysis includes all enrolled participants who took at least one injection during the treatment period. The risk sets accompanying the adverse-event counts are reported in the registry record. The record does not explain whether there were endpoint-specific exclusions, how incomplete follow-up was handled, or whether participants with missing safety information were treated in any particular way.
Why distinguish serious from severe?
General statistical context: seriousness and severity describe different features of an adverse event. Severity refers to how intense an event is, while seriousness is a regulatory classification based on consequences or criteria. Therefore, an event classified as severe is not necessarily serious, and an event classified as serious is not necessarily described as severe. A report should keep these terms distinct rather than treating them as synonyms.
The endpoint lists both severe TEAEs and serious TEAEs, as well as discontinuation due to adverse events and death. The registry record supplies serious-event counts and selected serious-event terms, but it does not report full numerical results for every endpoint component. The individual results for severe TEAEs and discontinuations because of adverse events are not reported in the registry record.
What can the design estimate?
General statistical context: a single-group study can estimate the frequency of observed events among participants under the study conditions. A randomized comparison can additionally estimate a between-group contrast, subject to its assumptions and limitations. With no comparator arm, there is no within-trial contrast for estimating how event frequency differs from another treatment group.
This extension is open-label and single-group. Consequently, the recorded event percentages describe the participants in the extension rather than a comparative treatment effect. The record does not report a randomized allocation, a masking procedure, or an analysis that adjusts the event frequencies against an external reference group. It would be inappropriate to turn these descriptive data into a claim that the intervention caused or prevented the listed events.
How should uncertainty be considered?
General statistical context: estimates from a study population are subject to sampling uncertainty. A confidence interval communicates uncertainty around an estimate under specified statistical assumptions. For event proportions, the interval can be especially informative when events are uncommon, because the observed proportion alone may not convey how imprecisely the underlying frequency is estimated.
Confidence intervals for the reported adverse-event figures are not reported in the registry record. P-values and adjusted estimates for the primary endpoint are also not reported. The record therefore supports reading the counts and percentages as descriptive observations, without assigning a formal inferential interpretation to them.
What do planning calculations mean?
General statistical context: a sample-size calculation asks how many participants might be needed under particular assumptions to detect a specified effect with a chosen statistical procedure. Such a calculation is a planning illustration, not evidence that a study had a particular probability of detecting an effect after the results were observed. It does not replace the actual observed results or resolve uncertainty in a single-group design.
The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of the observed effect. Those are assumptions for a planning illustration, not a description of this extension’s single-group design. The registry record does not report the trial’s own sample-size justification or a calculated sample-size result for this trial. Planning illustrations should therefore not be read as observed power or as evidence of a comparative effect in this study.
What is not specified?
The registry record does not report the statistical analysis plan, the methods used to calculate percentages, or the approach to missing data. It does not state whether interim analyses were planned or performed. It also does not report multiplicity procedures for the many listed outcome measures. These omissions limit assessment of how analyses were specified and whether any reported results were selected from a larger set of analyses.
General statistical context: transparency about analysis populations, missing-data handling, and multiplicity helps readers understand how estimates were produced and how much confidence to place in them. Missing outcomes can affect interpretation if participants with incomplete follow-up differ from those with complete data. Testing many outcomes can also increase the chance of a nominally unusual result arising by chance. These general issues cannot be resolved without trial-specific information, which is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 25 outcome measures, including the primary safety endpoint and secondary outcomes covering suicidal ideation, extrapyramidal symptoms, body temperature, heart rate, and supine blood pressure. The record does not report whether the investigators adjusted for multiple outcomes or multiple analyses, or whether any outcomes were designated as exploratory. A multiplicity strategy is therefore not reported in the registry record.
General statistical context: when many outcomes or comparisons are examined, the chance of encountering an apparently unusual result by chance can increase. Adjustment methods or a clearly prespecified hierarchy can help readers interpret a family of tests. Without information on the statistical plan, the degree to which outcome analyses were prespecified or adjusted cannot be assessed. The registry lists 0 analyses, so it does not provide analysis-level results or methods for these outcomes.
The safety population is described: all enrolled participants who took at least one injection during the treatment period. The record does not report further analysis populations for each endpoint, whether any participants were excluded from particular analyses, or how incomplete outcome information was handled. Details about missing-data methods, follow-up completeness, and reasons for missing observations are not reported in the registry record.
These gaps matter because the interpretation of an event percentage depends on who was included in its denominator and how missing information was treated. General statistical context: if participants with incomplete follow-up differ systematically from those with complete follow-up, a complete-case summary may not represent the whole enrolled group. The record does not provide enough information to assess whether that concern applies in this trial.
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 |
|---|---|---|---|
| Aripiprazole IM Depot 400/300 mg | 5 | 74 | 6.8% |
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 |
|---|---|
| Aripiprazole IM Depot 400/300 mg | 40 of 74 |
Most frequent serious adverse event terms
| Event term | Organ system | Aripiprazole IM Depot 400/300 mg |
|---|---|---|
| Depression | Psychiatric disorders | 2 of 74 |
| Schizophrenia | Psychiatric disorders | 2 of 74 |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | 1 of 74 |
| Suicidal ideation | Psychiatric disorders | 1 of 74 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Aripiprazole IM Depot 400/300 mg |
|---|---|---|
| Weight increased | Investigations | 22 of 74 |
| Akathisia | Nervous system disorders | 9 of 74 |
| Weight decreased | Investigations | 6 of 74 |
| Headache | Nervous system disorders | 6 of 74 |
| Hyperlipidaemia | Metabolism and nutrition disorders | 4 of 74 |
Serious events with the highest arm-level rate: depression (2.7%), schizophrenia (2.7%), abortion spontaneous (1.4%), suicidal ideation (1.4%).
The adverse-event record lists 5 participants with serious adverse events among 74 at risk and 40 participants with another adverse event among 74 at risk. These should be read as the registry’s reported counts for the specified categories, not as a comparison between treatments. The registry also lists Depression and Schizophrenia at 2.7% each, and Abortion spontaneous and Suicidal ideation at 1.4% each, among the top serious-event terms.
The serious-event terms and the broader event counts describe different levels of detail. The listed terms do not account for every possible event category, and the record does not report whether a participant could have experienced more than one event or appear in more than one category. Counts should not be added or treated as mutually exclusive.
The death field is null. A null value does not establish that the observed number of deaths was zero; a death count is not reported in the registry record. The record also does not report confidence intervals for these safety counts. As a result, the figures are descriptive and their precision cannot be assessed from the registry record alone. Seriousness should not be confused with severity: the primary endpoint names both serious and severe TEAEs, but complete numerical results for both categories are not reported.
12. What the Result Does, and Does Not, Mean
The registry record documents an open-label, single-group extension in which participants received aripiprazole IM Depot and safety events were monitored through the specified treatment period. Its reported adverse-event counts and serious-event terms provide a descriptive account of events recorded among participants in that study. They do not estimate what would have happened in a comparable group receiving another treatment or no treatment.
The design also does not establish that the intervention caused any particular event. Events during treatment may arise for several reasons, and the study has no randomized comparator to help distinguish those possibilities. The extension’s entry process adds context: participants had completed the preceding trial, and entry was at the investigator’s discretion. The registry record does not report how this selection affected the characteristics of the extension population.
The study does not establish comparative effectiveness. The primary endpoint is focused on safety, and the record does not report a treatment-versus-control effect estimate. It also does not give complete numerical results for each primary-endpoint component, confidence intervals, or p-values. These absences limit conclusions about the magnitude and precision of the reported safety findings.
General statistical context: a descriptive result answers what was observed in the studied group, while a causal or comparative result requires a design and analysis suited to that question. A large or small observed event count alone does not settle whether an event is attributable to treatment, nor does it show what would occur in a different population or over a different duration.
The registry record is most useful for identifying the study’s design, treatment schedule, endpoint definitions, analysis population description, and reported adverse-event observations. It does not provide enough information to reconstruct the full statistical analysis, assess missing-data effects, or determine how outcome multiplicity was handled. Interpretations should remain within those boundaries.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction in clinical-trial statistics: describing safety events is not the same as estimating a comparative treatment effect. The extension was open-label and single-group, so its event counts and percentages characterize what was recorded among participants receiving the intervention. There is no randomized control arm within this study against which to estimate a difference.
The endpoint also demonstrates why definitions matter. The registry distinguishes treatment-emergent events from events defined by seriousness, severity, treatment discontinuation, or death. These categories address different questions and can overlap. Readers need the endpoint definition and observation period to understand what the reported proportion represents.
The setting is also relevant. Participants entered after completing a preceding trial, and the brief summary says entry was at the investigator’s discretion. Extension populations can differ from populations newly beginning treatment, so these observations should not automatically be generalized to all patients with schizophrenia. The registry record does not report enough information to quantify that selection or assess its effect.
Finally, the record illustrates the importance of reporting analysis details alongside outcome counts. Information about confidence intervals, missing data, multiplicity, and the statistical analysis plan would help readers assess precision and analytic choices. Those details are not reported in the registry record. The available evidence can therefore support a bounded description of the study and its recorded safety events, but not a broader comparative or causal conclusion.
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.
This extension has no concurrent comparator, random allocation, or masking. Its single-group, open-label design limits interpretation to descriptive observations and does not support a within-trial estimate of comparative safety or efficacy. It also cannot establish that a recorded adverse event was caused by the intervention.
Participants entered after completing Trial 31-12-291, with entry at the investigator’s discretion. This selection process may limit how well the extension population represents people who did not complete the preceding study or did not enter the extension. The registry record does not report the number of people who were eligible but did not enter, or the reasons for non-entry.
The title describes a 26-week extension, whereas the intervention description specifies treatment for 24 weeks and the primary endpoint timeframe is baseline to Week 24. The record does not explain this difference. The record also does not report dose-specific outcomes, how dose selection was made, or whether participants changed dose.
Several analysis details are not reported in the registry record, including the statistical analysis plan, confidence intervals, missing-data methods, interim analyses, and multiplicity procedures. Complete numerical results for every primary-endpoint component are also not reported. The death field is null, rather than a stated count. These gaps constrain assessment of precision, outcome completeness, and analysis choices.
The study is marked completed, but the registry record’s outcome details remain limited. The listed event counts and terms should not be treated as a complete account of all safety results or as comparative evidence. These limitations are specific to the design and the information recorded for this extension.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open-label, Extension Study of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in Patients With Schizophrenia — NCT01683058.
- Registry record last updated 2015-03-31; status last verified 2015-03.
- Results first posted 2015-03-31.
- 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
NCT01683058 is a completed phase 3, multicenter, open-label, single-group extension study in patients with schizophrenia. The registry lists enrollment of 74. Participants received aripiprazole IM Depot 400 mg or 300 mg once monthly for 24 weeks; entry followed Trial 31-12-291 and was at the investigator’s discretion. The primary endpoint concerned percentages of participants reporting specified adverse-event categories from baseline to Week 24.
The registry reports serious adverse events for 5 participants among 74 at risk and another adverse-event count of 40 among 74 at risk. It lists four serious-event terms with percentages. A death count is not reported in the registry record. The record does not report a randomized comparison, confidence intervals, p-values, a statistical analysis plan, missing-data methods, or multiplicity procedures. The findings are therefore best understood as descriptive safety observations from this extension, not as comparative or causal estimates.