Effects of Eltoprazine on Cognitive Impairment Associated With Schizophrenia (CIAS) in Adults

Inclusion Criteria:

• Males and Females, 18-65 years of age, inclusive, who meet the DSM-IV-TR criteria for schizophrenia.
• Must test negative for pregnancy at the time of enrollment based on a serum pregnancy test and agrees to use a reliable method of birth control during the study.
• Performance less than the maximum cutoff (in parentheses) for ONE of the following MATRICS Consensus Cognitive Battery (MCCB tests: i) Letter-number span (20); ii) HVLT total (31); and iii) CPT d-prime (3.47)
• Brief Psychiatric Rating Scale (BPRS) Hallucinatory Behavior or Unusual Thought Content item scores ≤ 5
• BPRS Conceptual Disorganization item score ≤ 4
• Simpson-Angus Scale total score ≤ 6
• Calgary Depression Rating Scale (CDRS) total score ≤ 10
• Able to complete the baseline MCCB validly as assessed by Chief Neuropsychologist or tester
• Wechsler Test of Adult Reading (WTAR) raw score ≥ 6
• Be treated with one of the following second generation antipsychotics: risperidone, olanzapine, quetiapine, asenapine, iloperidone or paliperidone for the previous two months, with no change in dose in the last month, or with injectable depot antipsychotics (fluphenazine, haloperidol decanoate, risperdal Consta or paliperidone sustenna) with no change in last 3 months
• Laboratory results must show no clinically significant abnormalities.
• Must have an electrocardiogram (ECG) with QTc measurement performed at Screening that is not clinically significant.
• Must have a negative drug screen.

Exclusion Criteria:

• Current treatment with one of the following antipsychotics: clozapine, aripiprazole, lurasidone or ziprasidone.
• Current treatment with any anti-cholinergic drug in doses above 2 mg daily for benztropine, 5 mg per day for trihexyphenidyl, and 50 mg day for diphenhydramine.
• Current treatment with benzodiazepines in doses above 10 mg of diazepam (or the equivalent of another drug).
• Patients with a DSM-IV diagnosis of alcohol or substance abuse (other than nicotine) within the last month or a DSM-IV diagnosis of alcohol or substance dependence (other than nicotine) within the last 6 months.
• Have a significant suicide attempt within one year of Visit 1, answered yes to question 3, 4 or 5 on the C-SSRS (screening form) at Visit 1, or are currently at risk of suicide in the opinion of the Investigator.
• Patients with a history of significant head injury/trauma.
• Patients with a clinically significant neurological, metabolic, hepatic, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorder. Insulin-dependent diabetics who are clinically stable and whose baseline fasting glucose is 200 or less may be included.
• Clinically significant abnormalities in physical examination, ECG, or laboratory assessments.
• Clinically significant renal disease (e.g. chronic renal insufficiency with Glomerular filtration rate (GFR) <60, inflammatory disease requiring medication, acute renal failure).
• Pregnant women or women of child-bearing potential, who are either not surgically-sterile or using appropriate methods of birth control.
• Women who are breast-feeding
• Have a thyroid stimulating hormone (TSH) level consistent with hyperthyroidism or hypothyroidism. Patients previously diagnosed with hyperthyroidism or hypothyroidism, who have been treated on a stable dose of thyroid supplement for at least the past 3 months, and who are clinically and chemically euthyroid will be allowed to participate in the study.
• Have significant prior or current medical conditions that, in the judgment of the investigator, could be exacerbated by or compromised by study drug.
• Have any medical condition that would increase sympathetic nervous system activity markedly. Patients who are taking a medication on a daily basis (for example, albuterol, inhalation aerosols, pseudoephedrine), that has sympathomimetic activity can be enrolled.
• Used monoamine oxidase inhibitors (MAOIs) during the 2 weeks (14 days) prior to Baseline Visit 1.
• Have used any SSRI, a 5HT1A agonist or other serotonin-mediated treatment for any reason during the 4 weeks prior to Baseline Visit 1.
• Have current hypertension despite treatment.
• Have received treatment within the last 60 days with a drug that has not received regulatory approval for any indication at the time of study entry.