Study Evaluating Vabicaserin in Subjects With Schizophrenia

Study Overview
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Brief Summary
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The primary purpose of this protocol is to establish the efficacy, safety, and tolerability of vabicaserin (SCA-136) using a once a day capsule in subjects with acute exacerbations of schizophrenia.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Risperidone-Referenced, Parallel-Group, Adaptive-Design Study of the Efficacy, Safety, and Tolerability of Vabicaserin (SCA-136) in Subjects With Acute Exacerbations of Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: vabicaserin
* Drug: risperidone
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy, men and women, aged 18 to 65. Hospitalization because of an acute exacerbation of schizophrenia with a diagnosis of schizophrenia established greater than 1 year. Ability to remain hospitalized for the duration of the screening period and for 4 weeks of double-blind treatment. Exclusion Criteria: Current Axis I primary psychiatric diagnosis other than schizophrenia (DSM-IV-TR criteria). Current diagnosis or history of substance abuse or dependence (DSM-IV-TR criteria), including alcohol (except for nicotine), within 3 months before baseline (day -1). Subjects taking high or chronic doses of benzodiazepine at the screening evaluation who, in the investigator's judgment, would be likely to have severe withdrawal symptoms upon discontinuation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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: 1<br> | Drug: vabicaserin<br>* This study will utilize a randomized, double-blind, placebo-controlled, comparator-referenced, multicenter, parallel-group adaptive design with placebo, risperidone (4 mg/day), and up to 7 treatment arms of vabicaserin (50, 100, 150, 200, 300, 400 and 600 mg/day) over the course of the study<br>|
| Active Comparator: 2<br>4mg/day | Drug: risperidone<br> <br> |
| Placebo Comparator: 3<br>matching placebo | Other: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Symptom Scale (PANSS) Total Score at Baseline | PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210; higher score indicates greater severity. | Baseline | 
| Change From Baseline in Positive and Negative Symptom Scale (PANSS) Total Score at Day 28 | PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210; higher score indicates greater severity. | Baseline, Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Symptom Scale (PANSS) Positive Subscale Score | PANSS positive subscale assesses positive symptoms associated with schizophrenia. The positive subscale consists of 7 items (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total positive subscale scores range from 7 to 49; higher score indicates greater severity. | Baseline, Day 7, 14, 21, 28 | 
| Positive and Negative Symptom Scale (PANSS) Negative Subscale Score | PANSS negative subscale assesses negative symptoms associated with schizophrenia. The negative subscale consists of 7 items (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total negative subscale scores range from 7 to 49; higher score indicates greater severity. | Baseline, Day 7, 14, 21, 28 | 
| Positive and Negative Symptom Scale (PANSS) General Psychopathology Subscale Score | General psychopathology subscale assesses general psychopathology symptoms associated with schizophrenia. The general psychopathology subscale consists of 16 items (somatic concern, anxiety, guilt feelings, tension, mannerisms/posturing, depression, motor retardation, uncooperativeness, unusual thought content, disoriented, poor attention, lack of judgment/insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total general psychopathology subscale scores range from 16 to 112; higher score indicates greater severity. | Baseline, Day 7, 14, 21, 28 | 
| Positive and Negative Symptom Scale (PANSS) Cognition Cluster Subscale Score | Cognition cluster subscale assesses cognitive symptoms associated with schizophrenia. The cognition cluster subscale score is a sum of 5 items from positive, negative and general psychopathology subscales (conceptual disorganization, difficulty in abstract thinking, poor attention, lack of judgment and insight, and preoccupation). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total cognition cluster subscale scores range from 5 to 35; higher score indicates greater severity. | Baseline, Day 7, 14, 21, 28 | 
| Percentage of Participants With Response As Per Positive and Negative Symptom Scale (PANSS) Total Score | Responders were defined as 20 percent (%) responders and 50 % responders. A 20% responder was a participant whose PANSS total score was decreased by at least 20% from baseline to the week of assessment. A 50% responder was a participant whose PANSS total score was decreased by at least 50 % from baseline to the week of assessment. PANSS total score assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210; higher score indicates greater severity. | Baseline, Day 7, 14, 21, 28 | 
| Clinical Global Impression - Severity (CGI-S) Score | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). | Baseline, Day 7, 14, 21, 28 | 
| Clinical Global Impression - Improvement (CGI-I) Score | CGI-I: 7-point clinician rated scale to assess global improvement in the participant's clinical state compared to baseline; range: 1 (very much improved) to 7 (very much worse). | Day 7, 14, 21, 28 | 
| Calgary Depression Scale for Schizophrenia (CDSS) Score | CDSS: 9-item clinician rated scale, validated for rating the severity of depressive symptoms in participants with schizophrenia. Each item is rated on a 4-point scale ranging from 0 (absent) to 3 (severe). CDSS total score is the sum of each item scores and ranges from 0 to 27; higher score indicates more severity of symptoms. | Baseline, Day 7, 14, 21, 28 |