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 Evaluating the Safety and Tolerability of Brexpiprazole in the Treatment of Adults With Borderline Personality Disorder (BPD) (NCT04186403), a non-randomized phase 2, phase 3 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and as Per Severity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04186403 |
| Phase | Phase 2, Phase 3 |
| Condition | Borderline Personality Disorder |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 201 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Otsuka Pharmaceutical Development & Commercialization, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Adults with borderline personality disorder who entered the safety sample after receiving at least 1 dose of study drug. The registry lists an enrollment of 201. The safety sample is defined by receipt of at least 1 dose of the investigational medicinal product, so the endpoint applies to treated participants rather than everyone who may have been screened or enrolled.
Intervention
Open-label brexpiprazole tablets at 2 to 3 mg/day, taken orally for up to 12 weeks. The study evaluated safety and tolerability; it did not describe a blinded treatment assignment during this extension.
Comparator
There was no randomized concurrent control group. Participants were classified according to whether they had received brexpiprazole or matching placebo in the preceding double-blind trial. Both groups received open-label brexpiprazole in this study, so prior-treatment groups are not a like-for-like comparison of current treatments.
Primary question
How many participants experienced treatment-emergent adverse events, including events described by severity, during open-label treatment and the post-treatment observation period? The registry record emphasizes safety and tolerability rather than a comparative estimate of clinical benefit.
The primary outcome counts participants with treatment-emergent adverse events (TEAEs). An event qualified as treatment-emergent when its onset was on or after the start of open-label treatment. The registry describes severity categories as mild, moderate, and severe, with definitions based on the degree of discomfort and effect on normal daily activity.
The recorded safety period begins at signing of informed consent and extends to 30 days after the last dose, for up to approximately 16 weeks. This makes the outcome a safety description over the specified observation period, not a measure of change in borderline personality disorder symptoms. The record lists additional safety outcomes, including potentially clinically significant ECG, vital-sign, and laboratory abnormalities, movement-related scale scores, and suicidal ideation and behavior. These outcomes provide context for the safety focus, but the primary question remains the frequency and severity of TEAEs.
3. Trial Design
This was a multicenter, open-label trial of brexpiprazole in adults with borderline personality disorder. The registry lists Phase 2 and Phase 3, a non-randomized allocation, no masking, and a single-group model. It reports enrollment of 201 and a completed status. The listed study dates run from 2020-01-13 to a primary completion date of 2021-09-22.
Although the adverse-event counts are separated into two groups, that separation reflects participants’ treatment in the preceding double-blind trial. The group labelled Prior Brexpiprazole 2-3 mg/Day had received blinded brexpiprazole at 2 to 3 mg/day previously; the Prior Placebo group had received matching placebo previously. In the open-label study, both groups received brexpiprazole tablets at 2 to 3 mg/day orally for up to 12 weeks.
This distinction matters for interpretation. The study did not randomly assign participants to brexpiprazole or placebo in the open-label period, and the registry explicitly cautions that the arms are not a like-for-like control comparison. Any difference in the posted adverse-event counts between the prior-treatment groups therefore cannot be attributed to a randomized contrast in current treatment. The prior assignment may also identify groups with different treatment histories, but details beyond those described in the record are not reported in the registry record.
The record defines the safety sample as participants who received at least 1 dose of the investigational medicinal product. Its primary outcome is a count of participants with TEAEs and by severity. The registry lists multiple secondary safety and symptom-scale outcomes, but a statistical analysis plan, methods for handling missing outcomes, and details about inferential comparisons 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.
Before assignment: A total of 203 participants with borderline personality disorder (BPD), who completed the previous double-blind trial (NCT04100096) were screened, out of which 201 participants were enrolled in this study. Of the enrolled participants, 90 received 2 to 3 milligrams per day (mg/day) brexpiprazole and 111 received brexpiprazole matching placebo in the previous double-blind trial.
Overall Study
| Stage | Prior Brexpiprazole 2-3 Milligrams Per Day | Prior Placebo |
|---|---|---|
| STARTED | 90 | 111 |
| Safety Sample | 88 | 111 |
| COMPLETED | 71 | 92 |
| NOT COMPLETED | 19 | 19 |
Reasons for not completing this period:
| Reason | Prior Brexpiprazole 2-3 Milligrams Per Day | Prior Placebo |
|---|---|---|
| Adverse Event | 1 | 8 |
| Lost to Follow-up | 7 | 3 |
| Physician Decision | 1 | 0 |
| Withdrawal by Subject | 7 | 8 |
| Other: Not Related to Covid-19 | 3 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety sample included all participants who received at least 1 dose of IMP.
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: Enrolled sample included all participants who signed an informed consent form (ICF) and were enrolled into the trial.
| Characteristic | Unit | Prior Brexpiprazole 2-3 mg/Day | Prior Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 90 | 111 | 201 | |
| Age, Continuous | years | 33.6 (SD 10.5) | 32.0 (SD 10.6) | 32.7 (SD 10.6) |
| Sex: Female, Male: Female | Participants | 71 | 92 | 163 |
| Sex: Female, Male: Male | Participants | 19 | 19 | 38 |
| Race/Ethnicity, Customized: Race – White | Participants | 72 | 89 | 161 |
| Race/Ethnicity, Customized: Race – Black or African American | Participants | 7 | 19 | 26 |
| Race/Ethnicity, Customized: Race – American Indian or Alaska Native | Participants | 2 | 0 | 2 |
| Race/Ethnicity, Customized: Race – Asian | Participants | 4 | 0 | 4 |
| Race/Ethnicity, Customized: Race – Native Hawaiian or Other Pacific Islander | Participants | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Race – Other | Participants | 5 | 2 | 7 |
| Race/Ethnicity, Customized: Ethnicity – Hispanic or Latino | Participants | 15 | 17 | 32 |
| Race/Ethnicity, Customized: Ethnicity – Not Hispanic or Latino | Participants | 75 | 93 | 168 |
| Race/Ethnicity, Customized: Ethnicity – Other | Participants | 0 | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and as Per Severity, measured over Signing of ICF up to 30 days post last dose of study drug (up to approximately 16 weeks).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who experienced treatment-emergent adverse events, with severity also specified. A TEAE is an adverse event whose onset is on or after the start of open-label treatment. The registry defines an adverse event as an untoward medical occurrence in a trial participant who has received an investigational medicinal product; the event need not be caused by the treatment.
Severity was assessed on a 3-point scale. Mild events involved discomfort without disruption to daily activity; moderate events involved discomfort sufficient to reduce or affect normal daily activity; severe events prevented normal daily activity or work. These categories describe intensity and functional impact, not whether an event was caused by treatment. The registry does not equate severity with seriousness, which is a separate safety classification.
Counting affected participants is useful in a safety study because it indicates how many people experienced an event during the defined observation period. It is a descriptive measure: it does not by itself establish a causal relationship, compare risk under randomized treatments, or account for differences in time observed. The posted primary outcome title includes severity, but a complete severity-specific breakdown is not reported in the registry record. The available adverse-event results give serious-event counts and counts in another listed event category.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports serious adverse events affecting 1 participant among the 88 at risk in the Prior Brexpiprazole 2-3 mg/Day group and 2 participants among the 111 at risk in the Prior Placebo group. It reports other adverse events affecting 8 participants among 88 at risk and 31 among 111 at risk, respectively. Deaths are reported as 0 in each group. These are descriptive counts from a non-randomized, open-label study, not estimates from a randomized comparison.
The group labels refer to treatment in the earlier double-blind trial, not different assigned treatments in the open-label period. Both groups received brexpiprazole during this study. The registry explicitly warns that the arms are not a like-for-like control comparison. Accordingly, the difference in posted counts should not be interpreted as an effect of brexpiprazole relative to placebo. The record does not report adjusted comparisons, confidence intervals, hypothesis tests, or a statistical analysis plan for these counts.
The primary outcome concerns TEAEs over a period beginning at informed-consent signing and extending to 30 days after the last dose, up to approximately 16 weeks. The definition of TEAE uses onset on or after the start of open-label treatment. The observation period and event-onset definition should be kept distinct: an event’s classification depends on its onset, while the stated timeframe describes the period covered by the safety outcome.
The serious-event terms listed as most frequent are Suicidal Ideation, 1.1%, and Contusion, 0.9%. Those percentages are presented in the registry as terms, without a group-specific allocation in the record. They should not be combined with the group-level participant counts or treated as a complete account of all serious events. The record also lists potentially clinically significant ECG, vital-sign, and laboratory abnormalities and several other safety measures, but their results are not reported in the registry record.
Counts communicate observed events, not their causes or their precision. Without a randomized concurrent control, a prespecified comparative analysis, and reported uncertainty estimates, the counts cannot establish whether event occurrence differed because of treatment. They also do not describe the experience of every person with borderline personality disorder; the safety sample comprises participants who received study drug. The registry’s evidence is most directly read as a safety description for the treated participants in this trial, organized by their earlier trial exposure.
9. Statistical Methods Explained
The record’s primary safety outcome is a participant count, rather than a continuous measure or a time-to-event estimate. The distinction matters: a count of affected participants tells how many people had at least one event in the relevant category, but does not show how many episodes each person experienced, how long each event lasted, or the time at risk for each participant. The registry does not report those details for the primary outcome.
What does a participant count describe?
A participant count is a straightforward descriptive statistic. It focuses on people who experienced an event rather than on the total number of event episodes. For safety interpretation, this can be helpful because repeated events in the same person do not automatically make that person count as several participants. However, a count alone does not convey how common an event is in a broader population or whether a treatment caused it. It is tied to the safety sample, event definition, and observation period used in the study.
The registry lists the number at risk as well as the number affected for the serious and other adverse-event categories. Those denominators are useful context for reading the counts, but the record does not provide uncertainty intervals or a statistical comparison for them. No rates based on person-time are reported. If participants had different observation durations, a simple count would not account for that difference; whether duration varied in this study is not reported in the registry record.
Why does the design affect comparisons?
Random allocation is a general method for making treatment groups more comparable at the point of assignment. Here, allocation is listed as non-randomized, masking as none, and the model as single group. The two adverse-event categories distinguish participants by the treatment they received in an earlier double-blind trial. During the present open-label study, both categories received brexpiprazole. That history-based grouping does not create a concurrent placebo control, and differences between groups can reflect prior treatment or other group differences as well as chance.
Open-label treatment also means participants and study personnel were not masked to the treatment in the study described. In general, knowledge of treatment may affect event reporting, recognition, or attribution. The registry record does not provide enough information to determine whether or how such influences affected these results. The adverse-event definition itself does not require a causal relationship to treatment, so an event counted as a TEAE should not automatically be described as caused by brexpiprazole.
What would an uncertainty interval add?
In general, a confidence interval expresses the precision of an estimated quantity under a specified statistical method and assumptions. An interval around a group-specific event frequency can convey that the observed count is compatible with a range of underlying values; an interval around a group contrast can communicate uncertainty about the difference. Neither type of interval is reported for the adverse-event counts in the registry record. Without an interval or another inferential analysis, the counts should be read descriptively rather than as precise estimates of a treatment effect.
Small or uncommon event counts are especially difficult to interpret as comparative evidence because estimates can be imprecise. General statistical reasoning would call for attention to the event definition, relevant denominator, observation time, and uncertainty, not just the raw count. The registry record does not report a planned comparison or a model for these data, so no model-based conclusion can be reconstructed from the posted counts alone.
How should severity and seriousness be distinguished?
Severity describes the intensity of an adverse event in the registry’s mild, moderate, and severe categories, defined by discomfort and disruption to daily activity. Seriousness is a separate classification used for serious adverse events. An event can be severe without necessarily meeting a seriousness criterion, and an event classified as serious need not be the most severe by the study’s symptom-intensity scale. The listed serious-event counts therefore do not substitute for the primary endpoint’s severity breakdown. That breakdown is not reported in the registry record.
The record lists the primary outcome timeframe as signing of informed consent up to 30 days after the last dose, up to approximately 16 weeks. It defines a TEAE by onset on or after open-label treatment begins. In general, an event’s onset rule and the period during which events are collected jointly determine which observations qualify. Interpretations should not silently extend the endpoint beyond the specified observation period.
What do the planning illustrations mean?
Planning illustrations based on an observed effect are not observed power and are not results of this trial. As a general matter, such calculations depend on assumptions about the effect to detect, the significance level, allocation, and statistical approximation. The registry describes its illustrations as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated convention is a total event count; for other outcomes, it is participants per arm.
Those assumptions are not the trial’s own design justification. The registry record does not report a sample-size justification, and the study’s non-randomized, open-label structure differs from the equal-allocation planning assumption. A planning illustration cannot turn the observed groups into randomized arms, resolve confounding, or demonstrate that a safety difference is absent. It is a design aid for considering a future study under stated assumptions, not evidence about treatment efficacy or safety beyond the observed data.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes alongside the primary TEAE endpoint. These include potentially clinically significant ECG, vital-sign, and laboratory abnormalities; changes in the Simpson-Angus Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Rating Scale; and suicidal ideation and behavior assessed by the Columbia-Suicide Severity Rating Scale. The outcomes span event counts and changes in scale scores, so they address different aspects of safety and tolerability.
When a study evaluates multiple outcomes, general statistical practice considers multiplicity: repeated testing can increase the chance of at least one apparently unusual result even if no underlying effect exists. The registry record does not report a multiplicity adjustment, a hierarchy for interpreting secondary outcomes, or a statistical analysis plan. It also lists no statistical analyses. Therefore, the reported outcomes should not be treated as a coordinated set of confirmatory tests, and the record does not establish how any multiplicity was handled.
Missing-data methods are not reported in the registry record. The endpoint’s safety population is defined as participants who received at least 1 dose of study drug, but the record does not describe how participants with incomplete follow-up, missing assessments, or treatment discontinuation were handled in analyses. It also does not report imputation or sensitivity analyses. This limits assessment of whether the available observations represent the full intended safety follow-up.
The safety population definition gives a clear inclusion principle for the primary endpoint, but additional analysis-population definitions are not reported in the registry record. These omissions matter when interpreting counts and scale changes because the number of observed assessments may differ across outcomes. The record’s counts remain descriptive within their stated groups and denominators; missingness and multiplicity cannot be resolved from those counts alone.
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 2-3 mg/Day | 1 | 88 | 1.1% |
| Prior Placebo | 2 | 111 | 1.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Prior Brexpiprazole 2-3 mg/Day | 0 of 90 |
| Prior Placebo | 0 of 111 |
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 2-3 mg/Day | 8 of 88 |
| Prior Placebo | 31 of 111 |
Most frequent serious adverse event terms
| Event term | Organ system | Prior Brexpiprazole 2-3 mg/Day | Prior Placebo |
|---|---|---|---|
| Suicidal Ideation | Psychiatric disorders | 1 of 88 | 1 of 111 |
| Contusion | Injury, poisoning and procedural complications | 0 of 88 | 1 of 111 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Prior Brexpiprazole 2-3 mg/Day | Prior Placebo |
|---|---|---|---|
| Insomnia | Psychiatric disorders | 5 of 88 | 6 of 111 |
| Akathisia | Nervous system disorders | 1 of 88 | 9 of 111 |
| Fatigue | General disorders | 1 of 88 | 7 of 111 |
| Restlessness | Psychiatric disorders | 1 of 88 | 7 of 111 |
| Weight increased | Investigations | 0 of 88 | 6 of 111 |
Serious events with the highest arm-level rate: suicidal ideation (1.1%), contusion (0.9%).
The serious adverse-event figures are participant counts by prior-treatment group. The Prior Brexpiprazole 2-3 mg/Day group reports 1 serious adverse event among 88 at risk; the Prior Placebo group reports 2 among 111 at risk. The registry reports 0 deaths in both groups. These figures describe the recorded safety experience during the study’s specified observation period and should not be read as a randomized comparison.
The registry separately lists Suicidal Ideation at 1.1% and Contusion at 0.9% among the most frequent serious-event terms. Those term percentages are not assigned to a particular prior-treatment group in the record, so they cannot be used to infer a group-specific pattern. Nor do the two listed terms necessarily represent every serious adverse event recorded.
Seriousness should not be confused with the primary endpoint’s severity categories. The latter describe mild, moderate, or severe impact on daily activity; serious-event status is a distinct safety classification. The registry does not report the full severity-specific TEAE breakdown, event-level detail, or uncertainty estimates for the serious-event counts. These figures are therefore best treated as descriptive safety information, not as proof of causation or evidence from a controlled comparison.
12. What the Result Does, and Does Not, Mean
The results document adverse events reported among participants who received open-label brexpiprazole, with counts organized by whether participants had received brexpiprazole or placebo in the preceding trial. The record reports serious adverse events, other adverse events, and deaths by those prior-treatment categories. It also identifies serious-event terms and describes a broader set of intended safety outcomes. This provides a registry-based account of the study’s safety focus and its observed event counts.
These results do not establish that brexpiprazole caused a particular event. The registry’s adverse-event definition explicitly does not require a causal relationship to treatment. Nor do the data establish a comparison of current brexpiprazole against placebo: all participants received open-label brexpiprazole in this study, and the groups are based on past exposure rather than randomized current assignment. The registry explicitly cautions that the arms are not a like-for-like control comparison.
The counts also do not establish that no risk exists when a category has a low count or no deaths. A count is limited to the participants observed, the event definitions, and the safety period. The record does not provide confidence intervals, a comparative statistical analysis, or details on missing-data handling to quantify uncertainty or evaluate completeness of follow-up. Results should not be generalized automatically beyond the study’s treated safety sample.
The study was designed to evaluate safety and tolerability, and its primary endpoint reflects that purpose. The registry does not provide a primary efficacy endpoint or a controlled estimate of symptom benefit. Scale-based and other secondary outcomes are listed, but their results are not reported in the registry record. Accordingly, this evidence supports a descriptive reading of observed safety events, not a conclusion about efficacy, comparative safety, or the experience of all adults with borderline personality disorder.
13. Why This Trial Matters Statistically
This trial illustrates why design labels and group definitions are central to statistical interpretation. The adverse-event results are divided by participants’ earlier trial treatment, but that division does not create a randomized control in the open-label study. Both groups received brexpiprazole during the current study. Treating their counts as a direct treatment-versus-placebo contrast would misstate the design and overstate what the data can establish.
The endpoint also illustrates the difference between describing an event and attributing it. A TEAE is defined by timing relative to treatment initiation, not by proof that treatment caused it. The registry’s severity scale reflects impact on daily activity, while serious adverse events are reported as a separate category. Keeping timing, severity, seriousness, and causal attribution distinct is essential when reading safety results.
The record makes clear that safety summaries are tied to a defined treated population and follow-up period. Counts are interpretable only alongside those definitions, the relevant group denominators, and the limitations of the observation process. Here, the safety sample includes participants who received at least 1 dose, and the outcome period extends from informed-consent signing through 30 days after the last dose, up to approximately 16 weeks.
Finally, the registry distinguishes descriptive outcomes from inferential analyses. It reports event counts but no statistical analyses or uncertainty estimates for the comparison. Its planning assumptions are illustrative rather than evidence of observed power or a design rationale. Together, these features make the study useful as an example of how registry data can document safety experience while still leaving substantial limits on causal and comparative claims.
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 main limitation for comparative interpretation is the non-randomized, open-label design. The two reported groups are defined by treatment in a preceding trial, and both received open-label brexpiprazole in the current study. The registry explicitly states that the arms are not a like-for-like control comparison. Group differences may therefore reflect treatment history or other differences rather than a causal effect of current treatment.
The record reports counts but does not report confidence intervals, hypothesis tests, adjusted analyses, or the statistical analysis plan. The primary outcome is described as TEAEs and by severity, but the full severity-specific results are not reported in the registry record. Results for the listed secondary outcomes are also not reported in the registry record. Consequently, the posted event counts cannot answer every question the outcomes were intended to address.
Missing-data handling and follow-up completeness are not reported in the registry record. The safety population includes participants who received at least 1 dose, but the record does not explain how incomplete observations or discontinuations were handled. It also does not provide event-level duration, person-time, or a description of how observation time may have varied.
The serious-event terms are listed with percentages but are not allocated to prior-treatment groups in the record. The terms should not be treated as an exhaustive list or linked to a particular group without further information. Finally, the study is a safety and tolerability evaluation; the registry record does not report a controlled efficacy analysis. These limitations constrain causal interpretation, precision, and generalizability beyond the treated participants described in the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluating the Safety and Tolerability of Brexpiprazole in the Treatment of Adults With Borderline Personality Disorder (BPD) — NCT04186403.
- Registry record last updated 2024-10-03; status last verified 2024-09.
- Results first posted 2024-10-03.
- 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
The registry describes a completed, multicenter, open-label brexpiprazole study in adults with borderline personality disorder, listed as Phase 2 and Phase 3. Allocation is non-randomized, masking is none, and the model is single group. Enrollment is listed as 201. Participants received brexpiprazole at 2 to 3 mg/day orally for up to 12 weeks; adverse-event counts are categorized by treatment received in the preceding double-blind trial.
The primary outcome is the number of participants with treatment-emergent adverse events and by severity. The safety sample includes participants who received at least 1 dose, and the observation period runs from informed-consent signing through 30 days after the last dose, up to approximately 16 weeks. The posted results include serious and other adverse-event counts and deaths by prior-treatment group. Because the groups were not randomized to current treatment, the counts are descriptive rather than a like-for-like comparison. Statistical analyses, uncertainty estimates, missing-data methods, and results for the listed secondary outcomes are not reported in the registry record.