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 A Clinical Study to Investigate the Effect of an Investigational Drug as an Added Medication to an Antipsychotic, in Adults With Schizophrenia, as Measured Positron Emission Tomography (PET) Imaging (NCT04038957), a na phase 1 study. The primary outcome is Change From Baseline in Dopamine Synthesis Capacity at Week 2 Using 18F-DOPA..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04038957 |
| Phase | Phase 1 |
| Condition | Schizophrenia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 22 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Otsuka Pharmaceutical Development & Commercialization, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Adults with schizophrenia were eligible. The study summary describes male and female participants aged 18 to 45 years old and says the study was conducted at two locations in the UK. Enrollment was 22.
Intervention
Participants received SEP-363856 as an added medication to an antipsychotic. The described dose was 50mg or 75mg, flexibly dosed once daily.
Comparator
There was no separate control group. The design is listed as single group, with allocation recorded as NA, so the study does not make a like-for-like comparison between treatment arms.
Primary question
The primary question was whether dopamine synthesis capacity, measured with 18F-DOPA PET, changed from baseline to Week 2 (Day 14) during adjunctive SEP-363856 administration. The registry record does not report the numerical change or its uncertainty.
This is a question about an imaging measure over a short assessment interval, not a randomized comparison of clinical outcomes. The registry identifies schizophrenia as the condition and SEP-363856 as the investigational drug. It describes the PET scans as occurring before and after administration of SEP-363856 alongside an antipsychotic medication.
Because there is no separate comparator group, the question is limited to the observed change over time within this study group. A within-group change alone cannot distinguish an effect of the added drug from other explanations, such as changes over time or measurement variability. The record does not report a numerical endpoint estimate, so the magnitude and precision of any observed change cannot be assessed from the registry results.
3. Trial Design
This was a phase 1, open-label, single-group study. The registry lists masking as none and allocation as NA. Enrollment was 22, and the study status is completed. The sponsor was Otsuka Pharmaceutical Development & Commercialization, Inc. The recorded study start was 2019-08-07, and primary completion was 2023-06-06.
SEP-363856 was given as an adjunct to an antipsychotic medication. The intervention description specifies flexible dosing of 50mg or 75mg once daily. The study summary describes participants aged 18 to 45 years old, male and female, and two study locations in the UK. It also describes an approximate study duration of 14 months; the registry record does not report further details about participants’ individual time in the study.
The primary assessment compared dopamine synthesis capacity at baseline with the Week 2 assessment, identified as Day 14. The measurement was obtained using 18F-DOPA PET scans. The registry describes a repeated measures ANOVA with time and striatal subregion as independent variables and dopamine synthesis capacity (Ki values) as the dependent variable. It states that the covariance matrix for each subject’s time and striatal subregion was unstructured.
There was no randomized or otherwise separate control arm listed. The design therefore describes change within one group rather than a treatment contrast. The registry record does not report a protocol-level rationale for the design, the planned sample-size justification, or details of any interim analyses.
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 | SEP-363856 |
|---|---|
| STARTED | 22 |
| COMPLETED | 20 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | SEP-363856 |
|---|---|
| Withdrawal by Subject | 1 |
| SUBJECT WAS WITHDRAWN DUE TO SAFETY REASON | 1 |
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 | SEP-363856 |
|---|---|---|
| Participants analysed | 22 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 22 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | Years | 32.5 (SD 6.68) |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 16 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 21 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 11 |
| Race (NIH/OMB): White | Participants | 8 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Dopamine Synthesis Capacity at Week 2 Using 18F-DOPA., measured over baseline and week 2.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Kicer |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in dopamine synthesis capacity at Week 2 using 18F-DOPA. Dopamine synthesis capacity was assessed with positron emission tomography scans performed before and after SEP-363856 was added to an antipsychotic medication. The stated timeframe was baseline and Week 2 (Day 14), and the outcome is expressed in Kicer. The registry describes the measured values as Ki values.
In general, an imaging measure can provide a biological or physiological measure that may be useful for investigating how a treatment period relates to a process in the brain. It is distinct from a direct measure of symptoms or everyday functioning. The registry identifies dopamine synthesis capacity as the target of measurement, but does not explain why this endpoint was selected or how a change in the measure should be interpreted clinically.
The primary outcome is a continuous measure, with the mean and standard deviation identified as the summary statistics. A mean describes the average measured value in a group; a standard deviation describes how spread out individual values are around that average. The registry record does not report the mean, standard deviation, or numerical change for this endpoint. As a result, the size and precision of the Week 2 change cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary imaging endpoint and an analysis approach, but does not report a numerical result for the endpoint. It gives no estimate of the mean change from baseline, no standard deviation for the change, and no inferential result such as a confidence interval or p-value. The registry record therefore does not establish the direction, magnitude, or precision of the observed change.
The study enrolled 22 participants in a single group. That number describes enrollment, not the number included in the primary analysis; the analysis population and the number with usable paired PET measurements are not reported in the registry record. Without those details, the reader cannot determine how many participants contributed to the baseline-to-Week 2 comparison or whether missing measurements affected the result.
In general, a confidence interval describes the range of values compatible with the data and the statistical method used. Its width communicates precision: a wider interval indicates more uncertainty about the estimated quantity. No confidence interval is reported for this endpoint, so precision cannot be evaluated. Likewise, without a reported estimate, there is no basis for judging whether the observed change was small or large on the endpoint’s scale.
The study was open-label and had no control group. This means the design does not compare the observed change with a contemporaneous group that did not receive SEP-363856. In general, an uncontrolled before-and-after result can describe what happened over the measurement interval in the participants assessed, but it cannot by itself separate the contribution of the intervention from other changes over time or measurement variation. The registry does not report a treatment-effect comparison against a control group.
The posted analysis description names time and striatal subregion as factors in a repeated measures ANOVA. However, no model results are reported, and no details of the estimated contrasts or their interpretation are available in the registry record. The listed analysis therefore indicates the stated analytical framework, not evidence of a particular result.
The registry includes sample-size planning assumptions for an illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe a planning illustration, not the single-group study design. Any such illustration is not an observed power calculation or evidence that the study had a particular probability of detecting an effect. The observed endpoint effect needed to interpret such a planning scenario is not reported in the registry record.
The appropriate reading is consequently narrow: this completed phase 1 study was designed to assess short-term change in an imaging measure during adjunctive administration, but the posted registry information does not allow the numerical outcome or its uncertainty to be evaluated.
9. Statistical Methods Explained
What does the repeated measures analysis address?
The registry states that a repeated measures ANOVA was conducted. In general, repeated measures methods are used when measurements are taken more than once from the same participant. Observations from one person may be related rather than independent, so an analysis can account for their within-person structure. The stated assessment involved baseline and Week 2 measurements, with striatal subregion also included in the model.
The registry identifies dopamine synthesis capacity, represented by Ki values, as the dependent variable. It identifies time and striatal subregion as independent variables. This describes which outcome and factors were included in the stated analysis, but does not provide the fitted estimates, test statistics, degrees of freedom, or results for any terms in the model. Those results are not reported in the registry record.
What does an unstructured covariance matrix mean?
The analysis description says the covariance matrix was unstructured for each subject’s time and striatal subregion. In general, a covariance matrix represents how measurements vary and relate to one another. An unstructured form allows the data to determine the covariance relationships rather than imposing a simpler pattern in advance. This flexibility can be useful when the relationships among repeated measurements are not assumed to follow a particular form. It can also require enough information in the data to estimate the relationships reliably. The registry record does not report diagnostic checks or further details about how the model was fitted.
How should the mean and standard deviation be read?
The outcome is continuous and the registry specifies the mean and standard deviation. In general, the mean is an average on the measurement scale, while the standard deviation describes variation among measured values around the mean. These summaries answer different questions: the mean describes the group’s central value, and the standard deviation describes dispersion. Neither is reported numerically for the primary result in the registry record. A standard deviation is also not the same as a confidence interval; the former describes variation among observations, while the latter describes uncertainty in an estimated quantity under a statistical method.
What can an unadjusted planning illustration tell a reader?
The registry describes sample-size assumptions for planning illustrations based on an observed effect. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not the design of this study: the trial is listed as a single group with no comparator arm. The illustrations should therefore not be read as the study’s observed power or as its original enrollment plan. In general, a planning calculation estimates the sample size that might be required under stated assumptions; it does not establish what a completed study found. The registry record does not report the primary outcome estimate needed to assess the observed effect underlying the illustration.
The record also distinguishes planning outputs by whether they represent participants per arm or total events for time-to-event settings. The primary endpoint in this study is continuous, not time-to-event. No planning sample-size result is reported in the registry record, so no required sample size can be stated for this outcome.
What can be concluded without a reported model result?
A method description alone does not show the size or direction of an estimated change. For interpretation, readers would ordinarily need the analyzed sample, the estimated baseline-to-Week 2 contrast, a measure of uncertainty, and enough information to understand the model’s output. The registry record does not report these numerical results. Consequently, it is possible to describe the planned endpoint and stated analysis, but not to evaluate statistical evidence for a change or its precision.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and one analysis. It does not report a multiplicity adjustment or explain whether additional analyses were conducted beyond those listed. In general, multiplicity concerns arise when multiple hypotheses or outcomes are tested: considering many results can increase the chance that at least one appears notable by chance. The record does not provide enough information to determine whether multiplicity was relevant to the full analysis plan or how it was handled.
Missing-data methods are not reported in the registry record. The description does not state how incomplete PET scans, unavailable Week 2 measurements, or other missing observations were handled. It also does not report the number of participants with endpoint data at each assessment. Enrollment of 22 should therefore not be treated as confirmation that all 22 contributed to the primary analysis.
The analysis population is not reported in the registry record. The record does not identify whether the analysis included all enrolled participants, only participants with paired measurements, or another defined group. It also does not describe any exclusions or the handling of protocol deviations. These omissions limit assessment of how closely the analyzed group may correspond to the enrolled group.
In general, missing observations can affect both the amount of information available and the interpretation of an estimated change, particularly if the availability of measurements is related to participant characteristics or outcomes. No assumptions or sensitivity analyses addressing missing data are reported. The registry record therefore does not allow an assessment of the potential influence of missingness on the primary result.
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 |
|---|---|---|---|
| SEP-363856 | 0 | 22 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| SEP-363856 | 0 of 22 |
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 |
|---|---|
| SEP-363856 | 19 of 22 |
Most frequent non-serious adverse event terms
| Event term | Organ system | SEP-363856 |
|---|---|---|
| Somnolence | Nervous system disorders | 14 of 22 |
| Dizziness | Nervous system disorders | 8 of 22 |
| Dry mouth | Gastrointestinal disorders | 4 of 22 |
| Headache | Nervous system disorders | 4 of 22 |
| Nausea | Gastrointestinal disorders | 3 of 22 |
| Vision blurred | Eye disorders | 2 of 22 |
| Fatigue | General disorders | 2 of 22 |
| Presyncope | Nervous system disorders | 2 of 22 |
| Insomnia | Psychiatric disorders | 2 of 22 |
The safety figures list 22 participants at risk for serious adverse events and zero with a serious adverse event. The same group has 22 participants at risk for other adverse events and 19 with an other adverse event. The registry lists zero deaths and no top serious adverse event terms.
These are counts for the listed SEP-363856 group. The count of 19 refers to the registry’s other-adverse-event category and should not be confused with the count of serious adverse events. The registry record does not provide event descriptions for that category in the information, nor does it provide exposure-adjusted rates or further detail about event timing.
In general, a zero count in a completed study means no events of that type were recorded among the participants included in that safety summary; it does not establish that such events cannot occur. Similarly, the count of participants with other adverse events does not by itself describe severity, duration, or causal relationship to treatment. The registry record does not report additional context needed to assess those aspects.
12. What the Result Does, and Does Not, Mean
The study addresses a focused statistical question: how dopamine synthesis capacity measured with 18F-DOPA PET changed from baseline to Week 2 during SEP-363856 administration alongside an antipsychotic. The registry identifies the measure, timeframe, population, and repeated measures analysis. It does not report the numerical primary result, so the size, direction, and precision of any change are unknown from the posted registry information.
The single-group, open-label design also defines what the study can establish. In general, a before-and-after change in one group describes the measurements made in that group over time. Without a separate comparator, it cannot isolate the contribution of SEP-363856 from other possible explanations for change. The registry does not report a randomized treatment comparison.
The endpoint is an imaging measure of dopamine synthesis capacity, not a direct measure of symptoms, functioning, or quality of life. The registry record does not report how the imaging measure relates to clinical outcomes or provide a clinical interpretation threshold. Therefore, even if a numerical change were available, its clinical meaning would require context that is not reported in the registry record.
The safety summary reports zero serious adverse events among 22 participants at risk, 19 participants with other adverse events among 22 at risk, and zero deaths. These counts describe the safety information in the registry record, but they do not establish that the intervention is free of risk or describe every feature of the events.
Overall, the record documents a completed phase 1 imaging study and its stated statistical approach. It does not provide the numerical endpoint result needed to assess whether dopamine synthesis capacity changed, how precisely it was estimated, or how such a change should be interpreted clinically.
13. Why This Trial Matters Statistically
This study is statistically notable for the kind of question it asks: a short-term, within-participant imaging assessment rather than a comparison between randomized treatment groups. Repeated measurements can make it possible to describe change over time in a participant group, while accounting for the fact that measurements from the same participant are related. The registry’s model description also includes striatal subregion, reflecting the structure specified for the imaging outcome.
The design makes the distinction between measurement and causal comparison especially important. A baseline-to-Week 2 contrast can describe observed change, but without a control group it cannot show how that change compares with what would have occurred without the added medication. This limitation applies even when a sophisticated repeated measures model is specified; model structure does not replace a comparator.
The study also illustrates why statistical methods and numerical results need to be read together. The registry describes a repeated measures ANOVA and an unstructured covariance matrix, but does not report the model estimates or their uncertainty. Without those results, readers can understand the intended analysis but cannot judge the evidence about the endpoint.
Finally, an imaging endpoint and a clinical outcome answer different questions. A study can be informative about a biological measurement without establishing how participants feel or function. In this record, neither the numerical imaging result nor a clinical interpretation is reported, making careful limits on inference central to reading the study.
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 statistical interpretation is that the registry record does not report the numerical primary outcome result. The mean change, standard deviation, uncertainty interval, and inferential result are not available in the record. The direction and magnitude of the observed endpoint change therefore cannot be evaluated.
The study had a single group, open-label design, with no separate comparator. As a result, any within-group change would not by itself distinguish the effect of SEP-363856 from other changes over time or measurement variability. The record does not report a randomized treatment contrast.
Enrollment was 22, but the analysis population and number of participants with usable PET measurements are not reported in the registry record. The handling of missing data, participant exclusions, and protocol deviations is also not reported. These details matter for understanding how much information contributed to the primary analysis and how representative the analyzed participants were of those enrolled.
The record does not report a multiplicity procedure, the rationale for the sample size, or interim analyses. It does describe planning assumptions for an illustration, but those assumptions are not the trial’s design and the numerical outcome underlying the observed-effect scenario is not reported. The registry also does not explain the clinical interpretation of a change in the PET measure or how that measure relates to clinical outcomes.
These limitations do not negate the endpoint or design description; they constrain what can be concluded from the registry information. The reported record supports description of the study methods and safety counts, but not evaluation of the numerical primary efficacy result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Clinical Study to Investigate the Effect of an Investigational Drug as an Added Medication to an Antipsychotic, in Adults With Schizophrenia, as Measured Positron Emission Tomography (PET) Imaging — NCT04038957.
- Registry record last updated 2024-12-27; status last verified 2024-12.
- Results first posted 2024-11-25.
- 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
NCT04038957 is a completed phase 1, open-label, single-group study sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. Enrollment was 22. The recorded start date was 2019-08-07, and primary completion was 2023-06-06.
The study assessed SEP-363856, flexibly dosed at 50mg or 75mg once daily, as an added medication to an antipsychotic in adults with schizophrenia. The primary endpoint was change from baseline in dopamine synthesis capacity at Week 2 using 18F-DOPA PET. The stated analysis was a repeated measures ANOVA with time and striatal subregion as factors.
The registry record does not report the numerical primary outcome result, its uncertainty, the analysis population, or missing-data methods. The safety summary lists zero serious adverse events, 19 participants with other adverse events among 22 at risk, and zero deaths.