An Evaluation of the Safety and Efficacy of ABT-925 in Subjects With Acute Exacerbation of Schizophrenia

• Brief Psychiatric Rating Scale [ Time Frame: Assessed at screening and weekly from baseline through week 42/premature discontinuation ] [ Designated as safety issue: No ]
  Subscale of PANSS (The Positive and Negative Syndrome Scale)
• Clinical Global Impression Severity score [ Time Frame: Assessed at screening and weekly from baseline through week 42/premature discontinuation ] [ Designated as safety issue: No ]
  Assesses the overall, absolute degree of illness at any point in time (refer to the degree of illness at the time of the visit and during the week prior to the visit).
• Calgary Depression Scale for Schizophrenia Total score [ Time Frame: Assessed at screening and weekly from baseline through week 42/premature discontinuation ] [ Designated as safety issue: No ]
  The CDSS (Calgary Depression Scale for Schizophrenia Total score) consists of items designed to assess the severity of symptoms of depression in the presence of schizophrenia such as depressed mood, hopelessness, guilt, and insomnia.
• Negative Symptom Assessment [ Time Frame: Assessed at screening and weekly from baseline through week 42/premature discontinuation ] [ Designated as safety issue: No ]
  The NSA (Negative Symptom Assessment) is a 16-item instrument plus a one-item global rating designed to measure specific negative symptoms in schizophrenia

• CGI Severity and Improvement
• Calgary Depression Scale for Schizophrenia (CDSS)
• Negative Symptoms Assessment (NSA)

The objective of this study is to explore the safety and efficacy of ABT-925 involving patients who meet the DSM-IV-TR (Diagnostic and Statistical Manual of Medical Disorders, Fourth Edition Text Revision) criteria for an acute exacerbation of schizophrenia or schizoaffective disorder.

To explore the safety and efficacy of ABT-925 treatment at three different doses for 6 weeks compared with placebo in subjects with a diagnosis of acute exacerbation of schizophrenia or schizoaffective disorder according to DSM-IV-TR criteria (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision).

• Drug: ABT-925
• Drug: Placebo

• Placebo Comparator: Sugar Pill
  Intervention: Drug: Placebo
• Experimental: Group 1 Part 1 - ABT-925
  Intervention: Drug: ABT-925
• Experimental: Group 1 Part 2 - ABT-925
  Intervention: Drug: ABT-925
• Experimental: Group 2 - ABT-925
  Intervention: Drug: ABT-925

Inclusion Criteria:

• The subject has a current primary diagnosis of schizophrenia or schizoaffective disorder; specifically, an acute exacerbation with prominent "active phase" symptoms, as described in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision criteria (and confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision). Subjects with schizophrenia may belong to any of the following subtypes: paranoid, disorganized, catatonic, or undifferentiated.
• The subject has a The Positive and Negative Syndrome Scale total score of greater than or equal to 60.
• The subject has a score of greater than 4 ("moderate") on at least 2 out of the following 5 The Positive and Negative Syndrome Scale positive symptoms: delusions, conceptual disorganization, hallucinatory behavior, grandiosity, suspiciousness/persecution.
• The subject is between 18 and 65 years old inclusive at the time of randomization.
• The subject has a reliable caregiver (if applicable) or an identified responsible (e.g., family member, social worker, nurse) who will support him/her to ensure compliance with treatment and outpatient visits. In addition, the subject must have an adequate place of residence.
• The subject agrees to be hospitalized for the duration of the Taper off/Washout Period and at least the first fourteen days of the Double-blind Period.

Exclusion Criteria:

• The subject has a body mass index greater than 35.
• The subject has any condition that in the opinion of the investigator is likely to place him/her at an unacceptable safety risk by entering the study or by treatment with ABT-925.
• The subject has a diagnosis of one or more of the following conditions: another primary Axis I disorder, including schizophreniform disorder, bipolar disorder or major depressive disorder; comorbid Axis II diagnoses, including borderline personality disorder and mental retardation. (Note: a diagnosis of depression not otherwise specified is acceptable for inclusion into the study).
• The subject has a diagnosis of substance or alcohol disorder (abuse/dependence according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision criteria), excluding nicotine, within one (1) month prior to the beginning of the Screening Period, or in the opinion of the investigator, a disorder that will interfere with the conduct of the study.
• The subject has a history of substance-induced psychotic disorder in the previous 6 months.
• The subject has evidence suggestive of treatment-resistant schizophrenia (i.e., lack of significant clinical improvement despite adequate courses and doses of at least two different antipsychotic medications during the previous 2 years; or adequate use of clozapine indicated for treatment-resistant schizophrenia).
• The subject has serious violent, homicidal or suicidal ideation in the opinion of the investigator.
• The subject has a screening QT interval corrected by Bazett formula interval of greater than 430 msec if male and greater than 450 msec if female.
• The subject's Liver Function Tests (Aspartate aminotransferases, Alanine aminotransferase or total bilirubin levels) are not within normal limits at screening.
• The subject has a diagnosis, history, or a positive serological result suggestive of liver disease including but not limited to hepatitis and Gilbert's Syndrome.
• The subject has received any of the following treatments within the time periods described: mood stabilizers or antidepressants during the 30 days prior to Screening; electroconvulsive therapy during the 3 months prior to Screening; clozapine during 60 days prior to Screening.
• The subject is currently receiving treatment with oral psychotropic medications or has received depot neuroleptics within one inter-injection interval.