Study of SM-13496 (Lurasidone HCl) in Patients With Schizophrenia

Study Overview
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Brief Summary
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The study evaluates the efficacy and safety of SM-13496 compared with placebo in patients with schizophrenia.

Official Title
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Randomized, Placebo-controlled, Double-blind, Parallel-group, Confirmatory Study of SM-13496 (Lurasidone HCl) in Patients With Schizophrenia <Phase III Study>

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: SM-13496 (lurasidone HCl)
* Drug: SM-13496 (lurasidone HCl)
* Drug: Placebo
* Drug: Risperidone


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Patient meets DSM-IV criteria for schizophrenia. Patient is 18 or older but younger than 75 years of age on the day of signing informed consent. Patient understands the objectives, nature, and other aspects of the study and voluntarily agrees to participate in the study by providing written informed consent. Main Exclusion Criteria: Patient has a history of neuroleptic malignant syndrome, water intoxication, or paralytic ileus. Patient has Parkinson's disease. Patient has a history or complication of malignancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SM-13496 (lurasidone HCl) 40mg<br>SM-13496 40 mg was administered orally once daily. | Drug: SM-13496 (lurasidone HCl)<br>* Lurasidone HCl: 40 mg/day<br>|
| Experimental: SM-13496 (lurasidone HCl) 80mg<br>SM-13496 80mg was administered orally once daily. | Drug: SM-13496 (lurasidone HCl)<br>* Lurasidone HCl: 80 mg/day<br>|
| Placebo Comparator: Placebo<br>Placebo was administered orally twice daily. | Drug: Placebo<br> <br> |
| Active Comparator: Risperidone<br>Risperidone was administered orally twice daily. | Drug: Risperidone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 (LOCF) | The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items and three subscales: the Positive subscale contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility; the Negative subscale contains seven questions to assess blunted effect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of motivation, and similar symptoms; and the General Psychopathology subscale addresses other symptoms such as anxiety, somatic concern, and disorientation. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS total score is the sum of all 30 items and ranges from 30 through 210. A higher score is associated with greater illness severity. | Baseline and Week 6 [Last Observation Carried Forward (LOCF)] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the PANSS Positive Subscales at Week 6 (LOCF) | The PANSS is comprised of 30 items and three subscales. The Positive subscale contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS Positive subscale score is the sum of all 7 items and ranges from 7 through 49. A higher score is associated with greater illness severity. | Baseline and Week 6 (LOCF) | 
| Change From Baseline in the PANSS Negative Subscales at Week 6 | The PANSS is comprised of 30 items and three subscales. The Negative subscale contains seven questions to assess blunted effect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of motivation, and similar symptoms. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS Negative subscale score is the sum of all 7 items and ranges from 7 through 49. A higher score is associated with greater illness severity. | Baseline and Week 6 (LOCF) | 
| Change From Baseline in the PANSS General Psychopathology Subscales at Week 6 (LOCF) | The PANSS is comprised of 30 items and three subscales. The General Psychopathology subscale addresses other 16 symptoms such as anxiety, somatic concern, and disorientation. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS General Psychopathology subscale score is the sum of all 16 items and ranges from 16 through 112. A higher score is associated with greater illness severity. | Baseline and Week 6 (LOCF) | 
| Proportion of Participants With Treatment-emergent Adverse Events (TEAEs) | Proportion of participants with treatment-emergent adverse events. An adverse event was defined as any untoward medical occurrence in a study participant who was taking a medicinal (investigational) product. Treatment-emergent adverse events (TEAEs) were defined as adverse events with a start date on or after the date of the first dose through the end of follow-up, or adverse events occurring before the date of first dose and worsening during the treatment or follow-up period. | From Baseline to up to 8 weeks | 
| Proportion of Participants With TEAEs Leading to Discontinuation |  | From Baseline to up to 8 weeks | 
| Proportion of Participants With Treatment-emergent Serious Adverse Events (SAEs) | Proportion of participants with treatment-emergent adverse events. An adverse event was considered serious if it met one or more of the following criteria: Resulted in death; Was life-threatening (i.e., a patient was at immediate risk of death at the time of the event, not an event where occurrence in a more severe form might have caused death); Required in-patient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect; Was considered to be an important medical event. | From Baseline to up to 8 weeks |