Confirmatory Study of DSP-5423P in Patients With Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Confirmatory Study of DSP-5423P in Patients With Schizophrenia (NCT02287584), a randomized phase 3 study. The primary outcome is Change in PANSS Total Score From Baseline at Week 6.

2. Clinical Question

The clinical question is framed around a short-term comparison during the double-blind treatment phase. The Week 6 outcome focuses on change in overall symptom severity rather than a single symptom or a longer-term outcome. Secondary outcomes listed in the registry include the proportion achieving a response, defined as 20% or greater improvement from baseline in PANSS total score at Week 6, and treatment continuation at 28 weeks and 52 weeks.

The existence of these planned outcomes does not establish that results were reported for them. In the registry information, their numerical findings are not reported. Nor does the listed open-label treatment phase create a randomized comparison across its full duration: the registry describes the phase as open-label and does not report a controlled comparison for it.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group phase 3 study sponsored by Sumitomo Pharma Co., Ltd. The condition listed is schizophrenia, and enrollment was 580. The registry record gives a start date of 2014-12, primary completion of 2018-12, and status of completed.

During the double-blind treatment phase, participants were assigned to placebo, DSP-5423P 40mg, or DSP-5423P 80mg, with once-daily application for 6 weeks. The placebo and active double-blind groups are also represented in the registry's safety records by placebo-to-flexible-dose, 40mg-to-flexible-dose, and 80mg-to-flexible-dose entries. Those later entries relate to an open-label treatment phase, so they should not be read as additional randomized comparisons at the primary endpoint.

Participants completing the double-blind phase could enter the open-label phase. The registry describes flexible daily dosing of 40, 60, or 80 mg for 28 weeks outside Japan or 52 weeks in Japan. The descriptions identify placebo-to-flexible-dose and active-to-flexible-dose pathways. The application site is given for the double-blind treatment as the back, chest, or abdomen; the open-label descriptions do not give a complete application-site detail in the registry information.

Randomization and masking are design features intended to reduce bias in treatment assignment and outcome assessment. The registry lists quadruple masking but does not identify, in the record information, which specific groups of people were masked. Allocation procedures, stratification factors, and details of the randomization sequence are not reported in the registry record.

The primary endpoint was measured at Week 6 in the mITT population, with change in PANSS total score analyzed using a mixed model for repeated measures during the double-blind treatment phase. The registry lists secondary outcomes related to response and treatment continuation. Numerical outcome estimates, analysis details beyond the stated method and population, and results for the secondary outcomes 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: In this study, 675 subjects provided informed consent, 580 of 606 subjects.

the Double-blind Phase

Reasons for not completing this period:

the Open-label Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: modified Intention-to-treat (mITT) population; Change in PANSS Total Score Using Mixed Model for Repeated Measures in the Double-Blind Treatment Phase

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: modified Intention-to-treat (mITT) population

6. Primary Endpoint

The registry lists the primary outcome as Change in PANSS Total Score From Baseline at Week 6, measured over Week 6.

The primary endpoint is change in PANSS total score from baseline at Week 6. PANSS is an interview-based measure of psychopathology in adults with psychotic disorders. Its 30 items cover positive symptoms, such as hallucinations and delusions; negative symptoms, such as emotional withdrawal and lack of motivation; and general psychopathology, including anxiety, somatic concern, and disorientation.

Each item is scored on an anchored Likert scale from 1 - 7. Values of 2 and above indicate the presence of symptoms at progressively greater severity. Item scores are summed into subscale scores and a total score. The total score ranges from 30 through 210, with a higher score associated with greater illness severity. Change from baseline expresses how the measured score differs from the participant's starting value during the study. In general, this can provide a way to compare symptom-score trajectories between randomized groups at a specified follow-up point.

The Week 6 time point concerns the double-blind treatment phase. The registry describes analysis in the mITT population using a mixed model for repeated measures. The primary outcome's numerical group results and treatment comparison are not reported in the registry record, so the direction, size, and precision of any observed difference cannot be assessed from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The named primary analysis is a mixed model for repeated measures of PANSS total score during the double-blind treatment phase. This approach is commonly used for continuous outcomes recorded at multiple visits. In general, it models the pattern of repeated measurements and allows estimation of group differences over follow-up while accounting for the fact that measurements from the same participant are related. The registry specifies the method and the mITT population, but does not report the model formula, covariance structure, fixed effects, visit schedule, or contrast used for the main comparison.

What does a repeated-measures model do?

In general, repeated-measures models use information from more than one measurement occasion rather than treating each visit as an unrelated observation. A model can estimate mean outcome patterns by treatment group and can account for within-participant association. This can be useful when follow-up measurements are incomplete, but the validity of the resulting estimates depends on the model and its assumptions. The registry record does not state the assumptions used for the analysis or how they were evaluated.

The primary endpoint is a continuous change score, and the registry identifies the parameter as a mean with standard error. A mean describes the average value in a group; a standard error describes the uncertainty in an estimated mean. A confidence interval, if reported, would communicate a range of values compatible with the data and analysis assumptions. Neither the mean changes nor their standard errors or confidence intervals are reported in the registry information, so no precision assessment is possible.

Why distinguish standard deviation from standard error?

As a general statistical distinction, a standard deviation describes variability among individual measurements, whereas a standard error describes uncertainty in an estimated quantity such as a mean. They answer different questions and should not be read interchangeably. The registry identifies standard error as the dispersion measure for the primary outcome, but does not provide the numerical estimates in this record information. It is therefore not possible to judge the degree of variability or the precision of a treatment contrast from that label alone.

The mITT population is the stated population for the primary outcome. The registry does not define the exact inclusion rules for this population, explain how participants were handled after randomization, or report the number included in each primary analysis group. The term should not be taken to mean that every randomized participant necessarily contributed to every analysis. Such details are not reported in the registry record.

What does masking contribute?

In general, masking can reduce the chance that knowledge of treatment assignment affects participant reports, clinical management, or outcome assessment. The registry describes the study as quadruple-masked. It does not specify which roles were masked or describe the procedures used to maintain masking. Random allocation is intended to make treatment groups comparable at baseline on average, but the registry's description does not give the sequence-generation or allocation-concealment details.

The planning assumptions described for sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrative effect is defined as a stated fraction of the observed effect. These are planning assumptions, not a report of the original trial's design rationale, and their values do not establish the study's actual power. The registry information does not report the original sample-size justification or the observed primary effect needed to interpret an effect-based planning illustration. Sample-size illustrations are planning tools, not evidence about the likelihood that the trial detected an effect.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a model's assumed variability. If it is ignored, uncertainty estimates can be too small, which may make intervals look too narrow and tests appear more decisive than warranted. This concept is relevant to some outcome models, especially for counts or proportions, but the primary outcome in this study is described as a continuous mean. The registry does not report an over-dispersion assessment, and there is no basis in the record information to assert that over-dispersion affected this analysis.

Several analysis details that would help a reader evaluate the primary estimate are not reported in the registry record: the treatment contrast and its scale, the handling of missing outcome measurements, the model's covariates, the covariance assumptions, and any sensitivity analyses. The registry also does not report whether interim analyses were planned or conducted. These omissions prevent a full reconstruction of the statistical analysis and should not be filled by assuming standard procedures.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and secondary outcomes, but the information does not describe a multiplicity-control strategy. Multiplicity arises when several outcomes, time points, groups, or statistical tests are examined. In general, conducting multiple tests can increase the chance of at least one apparently notable finding unless the analysis plan accounts for the number and relationship of the tests. The registry does not report whether the outcomes were tested under a hierarchy, adjusted together, or interpreted under another prespecified approach.

The primary outcome is change in PANSS total score at Week 6, while listed secondary outcomes include a response definition at Week 6 and continuation at 28 weeks and 52 weeks. The record information does not report numerical results for these outcomes or clarify how their tests relate to the primary analysis. The primary outcome information also indicates that the outcome has several categories or time points and is not reduced to one comparison. The registry's reported analysis details are not sufficient to identify a single estimate or reconstruct a multiplicity adjustment.

Missing-data handling is also not reported in the registry record. A repeated-measures model can use available measurements under particular assumptions, but naming that model does not establish which participants had missing values, why values were missing, or whether the assumptions were appropriate. No imputation method, sensitivity analysis, or missingness summary is described in the information.

The primary population is named as mITT, but the operational definition and analysis counts are not reported. The registry record does not explain how protocol deviations, treatment discontinuation, or incomplete outcome measurements affected inclusion. These gaps limit assessment of the analysis population and the robustness of any result; they do not establish that the analysis was inappropriate.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: schizophrenia (6.9%), psychotic disorder (3.1%), toxicity to various agents (1.0%), akathisia (1.0%), psychiatric symptom (1.0%).

The registry reports serious adverse event counts for six group entries. The entries are DSP-5423P Placebo, with 9 affected among 190 at risk; DSP-5423P 40mg, with 8 among 196; DSP-5423P 80mg, with 10 among 194; DSP-5423P Placebo-to-Flex, with 18 among 131; DSP-5423P 40mg-to-Flex, with 24 among 196; and DSP-5423P 80mg-to-Flex, with 29 among 194. These are counts of participants affected, as recorded, rather than counts of all event episodes.

For other adverse events, the recorded affected counts are 45 among 190, 62 among 196, 76 among 194, 60 among 131, 108 among 196, and 111 among 194, respectively, in the same group order. Death counts in that order are 0, 0, 1, 1, 0, and 4. These descriptions are limited to the registry's reported counts; they do not establish causality or provide a complete comparison of safety between treatment strategies.

The flexible-dose entries relate to the open-label phase, whereas the first three entries describe double-blind treatment groups. Participants completing the double-blind phase could enter the open-label phase, so the entries should not be added or treated as independent randomized arms. The registry lists serious-event terms including Schizophrenia at 6.9%, Psychotic disorder at 3.1%, and Toxicity to various agents, Akathisia, Psychiatric symptom, and Suicidal ideation at 1.0% each. The record does not provide an arm-specific breakdown for these terms in the information.

12. What the Result Does, and Does Not, Mean

The record establishes that a randomized, quadruple-masked, parallel-group phase 3 study was conducted to evaluate DSP-5423P compared with placebo in patients with schizophrenia. It identifies the Week 6 change in PANSS total score as the primary endpoint and names the mITT population and mixed model for repeated measures as the analysis basis. It also describes treatment pathways, secondary outcomes, and recorded adverse-event counts.

Those design details do not by themselves show the size or direction of the primary treatment difference. The numerical primary outcome results are not reported in the registry record. Without the group estimates, comparison, and uncertainty measures, the posted information cannot establish how different the mean changes were or how precisely that difference was estimated. A completed study status indicates that the trial is recorded as completed; it does not substitute for outcome estimates.

The listed safety counts are descriptive and cover both double-blind and open-label pathway entries. They should be interpreted in light of the different phases and should not be pooled by simply adding group counts. The counts alone do not determine whether an event was caused by treatment, and the record information does not provide a full accounting of event timing, duration, severity, or exposure-adjusted comparisons.

In general, a statistical estimate addresses the observed data under an analysis model; it does not by itself answer every clinical question. Interpretation would also depend on the size and precision of the effect, relevance of the measured outcome, and limitations in the study and reporting. Here, the absence of primary outcome estimates prevents that assessment. No conclusion that DSP-5423P did or did not improve symptoms follows from the information reported in this record.

The registry also does not provide enough detail to assess all analysis choices, including missing-data handling, multiplicity control, or the original sample-size justification. These are uncertainties about what can be evaluated from the record, not proof that a particular method was or was not used. The conclusions that can be drawn are therefore descriptive: the trial design and measured outcomes are documented, while the primary efficacy result is not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a randomized parallel-group comparison with a continuous symptom outcome measured over time. It defines a primary time point and names both the analysis population and repeated-measures method. Those features help identify the intended estimand and the kind of data analysis planned, even though the numerical primary results are not reported in the registry record.

The design also includes a transition from a double-blind treatment phase to an open-label flexible-dose phase. That distinction matters when interpreting outcomes across time. A randomized comparison during the double-blind period is not interchangeable with later observations in an open-label phase, and the registry's safety entries reflect both the initial groups and later pathways. Clear phase-specific interpretation avoids treating all listed records as parallel, independent treatment arms.

The record demonstrates why outcome reporting is essential to statistical interpretation. Knowing enrollment, design, endpoint, and model is not enough to evaluate the size, precision, or clinical relevance of a treatment contrast. Group estimates and uncertainty measures are needed to understand what the data indicate. Without them, readers cannot judge whether results were close to one another, how uncertain an estimated difference was, or whether the findings align with the study objective.

Finally, statistical transparency depends on more than naming an analysis method. Information about the model specification, missing data, analysis population, multiplicity, and sample-size rationale can materially affect how results are assessed. These details are not reported in the registry information. The trial therefore illustrates both the value of a clearly identified endpoint and the limits created when numerical outcomes and supporting analysis details are absent.

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 interpretation is that the registry information does not report numerical primary endpoint results. There are no reported group changes, treatment contrast, confidence interval, or primary p-value. This prevents assessment of effect direction, magnitude, and precision and means that the stated study objective cannot be evaluated using the posted outcome information.

The registry identifies the endpoint as change from baseline in PANSS total score at Week 6 and names mixed model for repeated measures in the mITT population. It does not provide a complete model specification, the definition of mITT, primary analysis counts, covariate details, or a description of missing-data handling. Sensitivity analyses and procedures for checking model assumptions are not reported in the registry record.

The record information does not explain the multiplicity strategy for the primary and secondary outcomes, or how several categories or time points in the primary outcome were handled. The original sample-size justification and whether interim analyses were planned or conducted are not reported in the registry record. The sample-size assumptions described for planning are illustrations and do not replace those missing protocol details.

The open-label treatment phase has flexible dosing and different stated durations outside Japan and in Japan. The information does not give complete details of treatment exposure or application site for that phase. Long-term continuation outcomes are listed, but their numerical results are not reported. Because participants could move from double-blind treatment into open-label treatment, later pathway records should not be interpreted as independent randomized groups without additional information.

Safety counts are reported for multiple group entries, but the record information does not supply a full event-level account or an arm-specific distribution of the listed serious-event terms. These limitations constrain safety comparisons and do not show that events were caused by treatment. Overall, these are limitations of what can be evaluated from the registry record; they should not be taken as evidence that unreported methods or results were absent from other study documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Confirmatory Study of DSP-5423P in Patients With Schizophrenia — NCT02287584.
• Registry record last updated 2022-04-12; status last verified 2022-04.
• Results first posted 2020-12-23.
• 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.

18. Record Summary

NCT02287584 is a completed randomized, quadruple-masked, parallel-group phase 3 study sponsored by Sumitomo Pharma Co., Ltd. It enrolled 580 patients with schizophrenia. The registry gives a start date of 2014-12 and primary completion of 2018-12.

The double-blind phase compared once-daily placebo with DSP-5423P 40mg or 80mg for 6 weeks. Participants completing that phase could enter an open-label flexible-dose phase. The primary outcome was change from baseline in PANSS total score at Week 6, analyzed in the mITT population using mixed model for repeated measures. Response at Week 6 and treatment continuation at 28 weeks and 52 weeks were listed as secondary outcomes.

The registry information includes adverse-event counts but does not report numerical primary outcome results, the primary treatment comparison, or its uncertainty. Several analysis details, including missing-data handling, multiplicity strategy, and the original sample-size justification, are not reported in the registry record.