Long-term Extension Study of SM-13496 (Lurasidone HCl) in Patients With Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-term Extension Study of SM-13496 (Lurasidone HCl) in Patients With Schizophrenia (NCT01614912), a na phase 3 study. The primary outcome is Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at LOCF Endpoint.

2. Clinical Question

3. Trial Design

This is a Phase 3, completed, single-group extension study of SM-13496 (lurasidone HCl) in patients with schizophrenia. The registry lists an enrollment of 284 and identifies the intervention as a drug. It records allocation as not applicable and masking as none. These features mean the record does not describe a randomized, masked comparison between treatment groups.

The study began in 2012-08, and primary completion was recorded as 2015-05. The primary endpoint timeframe is double-blind baseline through up to 32 weeks, using a last-observation-carried-forward endpoint. The registry does not explain how participants entered the extension, whether or how treatment doses were selected, or how long each participant was followed.

The adverse-event group is described as SM-13496 (Lurasidone HCl) 40-mg or 80-mg. This is a single-group description, not evidence of separate dose arms or a comparison between doses. Allocation details beyond not applicable are not reported in the registry record.

The listed secondary outcomes include change in CGI-S and PANSS subscale scores at the LOCF endpoint, as well as proportions with treatment-emergent adverse events, events leading to discontinuation, and serious adverse events. The record also lists the PANSS total-score change as the primary endpoint. The numerical outcome estimates, analysis results, and detailed statistical plan are not reported in the registry record, so the design description should not be mistaken for evidence about the magnitude of change or a treatment effect.

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

Analysis population for the primary outcome, as defined in the registry: ITT (intent-to-treat) population

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: ITT (intent-to-treat) population

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at LOCF Endpoint, measured over DB baseline and up to 32 weeks (LOCF endpoint).

The primary endpoint is change from baseline in the total score on the Positive and Negative Syndrome Scale, or PANSS, at the last-observation-carried-forward endpoint. Its timeframe is double-blind baseline through up to 32 weeks. The registry specifies a mean and standard deviation as the summary measures and identifies the ITT population.

The PANSS is an interview-based measure of psychopathology in adults with psychotic disorders. It combines 30 items across positive, negative, and general psychopathology subscales. Items are scored on an anchored Likert scale, and the total is the sum of the item scores. The registry notes that higher totals are associated with greater illness severity. The measure is used to summarize symptom severity, while its subscales provide separate views of symptom domains.

Change from baseline expresses the endpoint score relative to the participant’s baseline score. The registry does not report the mean change, its standard deviation, the number contributing to this endpoint, or an uncertainty interval. Consequently, the endpoint definition is available, but the numerical result and its precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized by a mean and standard deviation. It also names the ITT population and an endpoint based on last observation carried forward. These labels identify parts of the intended analysis, but the statistical analysis plan, model, and numerical output are not reported in the registry record.

What a mean change represents

For a continuous outcome, a mean change summarizes the average difference between baseline and endpoint scores among the observations included in the analysis. It gives a concise description of the group’s average course, but it does not show how varied individual participants’ changes were. The standard deviation describes variation among observations around the mean; it is not the same as the uncertainty in the estimated mean. A confidence interval, when reported, conveys the range of values compatible with the data and the stated method, subject to the assumptions used.

For this study, the registry identifies the mean and standard deviation as the summary measures, but does not report either value for the primary endpoint. It also does not report a confidence interval or a test of the primary outcome. The measure’s definition is therefore clearer than the result available in the registry record.

What LOCF means

Last observation carried forward is a missing-data procedure in which a participant’s most recent observed measurement is used in place of a later measurement that is unavailable. In general, this can allow an endpoint to be formed for participants without a measurement at the planned endpoint. However, the procedure relies on assumptions about how the outcome would have behaved after the last observation. If participants’ scores would have changed after that point, carrying the earlier value forward may not represent their unobserved endpoint.

These are general properties of LOCF, not a finding that the procedure biased this study’s results. The registry identifies LOCF in the endpoint description, but does not report the amount or pattern of missing data, the timing of last observations, or sensitivity analyses using alternative assumptions. The way LOCF was implemented in detail is not reported in the registry record.

What the ITT label tells us

Intent-to-treat generally refers to analyzing participants according to the group to which they were assigned, regardless of treatment received. In a single-group extension study with allocation recorded as not applicable, the label does not define a randomized assignment comparison. The registry names the ITT population for the primary endpoint, but does not provide operational rules for inclusion, handling of participants who discontinued, or the number analyzed.

Why design affects interpretation

This is a single-group study with no listed control group and no masking. In general, a single-group change estimate describes outcomes over time in the observed group but does not isolate the effect of treatment from other explanations for change. Lack of masking can also matter for subjective assessments, although the registry entries do not establish whether this affected the measurements in this study. These are general design considerations, not claims about what occurred.

The listed primary endpoint is a continuous score, whereas safety outcomes are reported as counts and proportions. These types of outcomes answer different descriptive questions. A score change summarizes a measured symptom scale; an adverse-event count describes the number of participants or events recorded under the registry’s definitions. Neither type alone supplies a controlled comparison.

What can be concluded from the statistical record

The registry lists eight outcome measures and zero analyses. It names the primary endpoint and several secondary outcomes, but the numerical outcome results and inferential statistics are not reported in the registry record. Without estimates and uncertainty measures, it is not possible to judge the precision of the primary result from these registry entries. Without a comparator, even a reported within-group estimate would not establish a comparative treatment effect.

Any sample-size illustrations on the page should be read as planning exercises, not as observed power. The stated assumptions describe a two-sided significance level of 0.05, equal allocation between two hypothetical arms, a normal approximation, and an effect defined as a fraction of an observed effect. Such illustrations are not the study’s own design justification or a substitute for its outcome analysis. The sample-size justification and detailed analysis choices are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("SM-13496 (Lurasidone HCl) 40-mg or 80-mg Group")
n   <- c(281)
m   <- c(-28.4)
sp  <- c(22.2)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  SM-13496 (Lurasidone HCl) 40-mg or 80-mg Group  281  -28.400  22.200  -31.007  -25.793

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary PANSS total-score endpoint and secondary outcomes covering CGI-S, PANSS subscales, and safety measures. It does not report how many statistical hypotheses were formally tested, whether testing followed a hierarchy, or whether any adjustment for multiple comparisons was planned. The multiplicity strategy is not reported in the registry record.

Multiplicity matters when several outcomes or analyses are examined. In general, the more opportunities there are to identify a result as statistically notable, the more important it is to understand whether the analysis accounted for that testing structure. This general point does not establish that any particular result in this study is misleading. Since the registry record provides no analyses or p-values, the impact of multiplicity cannot be assessed.

Missing data are relevant because the primary endpoint uses last observation carried forward. The record does not report how many participants lacked endpoint measurements, why observations were missing, or whether the likelihood of missingness differed across participants. It also does not report sensitivity analyses or an alternative missing-data method. General concerns about LOCF assumptions apply, but their practical effect on this study’s estimate cannot be determined from the record.

The primary endpoint specifies the ITT population, but the number included in that analysis and the detailed population rules are not reported. Enrollment was 284, whereas 282 were listed at risk in the safety group; the record does not explain this distinction. The reasons participants may have been excluded from any analysis are not reported in the registry record. These omissions limit assessment of how complete and representative the analyzed outcome data were.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: schizophrenia (6.0%), hyponatraemia (0.7%), psychotic disorder (0.7%), methaemoglobinaemia (0.4%), acute coronary syndrome (0.4%).

The safety summary describes one group of SM-13496 (Lurasidone HCl) 40-mg or 80-mg, with 282 participants at risk. It records 31 participants with serious adverse events, 184 with other adverse events, and one death. These are separate entries in the safety summary; the registry does not provide enough detail to determine overlap between categories or to infer the number of total events.

The listed serious-event terms include Schizophrenia at 6.0%, Hyponatraemia at 0.7%, Psychotic disorder at 0.7%, Methaemoglobinaemia at 0.4%, Acute coronary syndrome at 0.4%, and Cardiac failure congestive at 0.4%. The percentages are reported as event-term listings. The registry record does not explain whether a participant could contribute to more than one term, or how repeated events were handled.

These figures describe what was recorded during the study; they do not establish causation. A serious adverse event is not necessarily caused by the intervention, and the record does not report event-level attribution or a comparison group. The single reported death should likewise be read as a safety count, not as evidence about cause. The registry does not provide a control rate or detailed timing that would support a comparative safety assessment.

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

This record is useful for identifying the study’s clinical question, outcome definitions, design, and selected safety counts. It describes a Phase 3 extension study in patients with schizophrenia, with change in PANSS total score as the primary endpoint. The measure is clinically interpretable as a symptom-severity scale, and the record states that higher scores are associated with greater illness severity.

What the record does not provide is the primary mean change, its standard deviation, a confidence interval, or an inferential analysis. Therefore, the size, direction, and precision of the primary outcome cannot be described from these registry entries. The absence of those estimates should not be interpreted as evidence of no change; it means the numerical result is not reported in the registry record.

The single-group design means there is no contemporaneous comparator in the record. In general, observed change over time in one group cannot determine how outcomes would have differed under another treatment or no treatment. This is a design limitation on causal and comparative interpretation, not a claim that any particular alternative explanation occurred in this study.

The safety counts and listed event terms provide descriptive information, but do not establish that events were caused by SM-13496. With no comparator safety data reported, the figures cannot show whether event frequency was higher or lower than under another condition. The record also does not report enough detail to assess recurrence, timing, or attribution for the listed terms.

Accordingly, the posted information supports a description of the study’s intended endpoint and selected safety observations. It does not support a conclusion about the magnitude or certainty of a treatment effect, nor a comparative safety conclusion. Those questions would require results and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial matters statistically because its design and endpoint make clear the difference between describing change and estimating a comparative effect. The study is a single-group extension with no listed control and no masking. It identifies a continuous symptom-severity endpoint and a defined observation window, but the registry record does not report the endpoint estimate or its uncertainty.

That distinction is important when reading longitudinal clinical data. A before-and-after summary can characterize a group’s observed course, but the lack of a comparator limits what can be attributed to the intervention. In general, changes over time may have multiple explanations. The record does not allow those explanations to be separated statistically.

The LOCF endpoint also highlights how missing-data choices matter. LOCF can produce an endpoint when a later measurement is unavailable, but it assumes that the last measured value is an acceptable stand-in for later unobserved values. This is a general methodological concern. The record does not provide missingness details or sensitivity analyses to show how robust the result might be under other assumptions.

Finally, the registry separates a clearly named primary measure from a list of secondary clinical and safety outcomes, yet does not report analyses. The distinction between an outcome being specified and a result being available is essential: an endpoint definition alone cannot tell readers what was observed or how precisely it was estimated. Here, the design and measure are visible, while the primary numerical result and inferential conclusions are not reported in the registry record.

15. 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 trial-specific limitation is the absence of reported primary outcome estimates. Although the registry names PANSS total-score change, its mean, standard deviation, number analyzed, and confidence interval are not reported in the registry record. The result’s magnitude, direction, and precision therefore cannot be assessed from the registry entries.

The study is single-group, with allocation recorded as not applicable and masking recorded as none. There is no like-for-like control comparison in the record. Thus, the design cannot establish a comparative treatment effect from within-group change alone. This does not determine whether the intervention changed scores; it limits the causal interpretation that can be made from the design.

The endpoint uses LOCF, but the registry does not report the extent or pattern of missing data, implementation details, or sensitivity analyses. The number included in the ITT endpoint analysis is also not reported. Enrollment was 284, while the safety group lists 282 at risk; the record does not explain this difference.

The safety summary does not provide event attribution, timing, or a comparator rate. It is therefore descriptive and cannot establish causation or comparative risk. The registry also does not report the detailed statistical plan, multiplicity handling, or sample-size justification. These absences limit evaluation of the analyses and of the precision intended by the study design.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long-term Extension Study of SM-13496 (Lurasidone HCl) in Patients With Schizophrenia — NCT01614912.
• Registry record last updated 2022-04-12; status last verified 2022-04.
• Results first posted 2018-10-19.
• 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.

19. Record Summary

The registry describes a completed Phase 3, single-group extension study of SM-13496 (lurasidone HCl) in patients with schizophrenia. Enrollment was 284. The primary endpoint was change from baseline in PANSS total score at a LOCF endpoint, through up to 32 weeks, in the ITT population.

The record lists secondary symptom and safety outcomes. In the safety group of 282 at risk, it reports 31 participants with serious adverse events, 184 with other adverse events, and one death. The primary outcome estimates, inferential analyses, detailed statistical plan, and comparator data are not reported in the registry record. The available information supports design and safety-description summaries, but not a numerical assessment of the primary endpoint or a comparative treatment conclusion.