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

Schizophrenia is a common and highly disabling psychiatric disorder with population
prevalence around 1%. The manifestations of schizophrenia fall into three major domains: 1)
"positive" symptoms, such as delusions, hallucinations, and disorganization of behavior; 2)
"negative symptoms," including social withdrawal, lack of motivation, and reduced expression
of affect; and 3) cognitive dysfunction. Cognitive deficits are seen in most patients with
schizophrenia.

Eltoprazine has agonist effects on both 5-HT1A and 5-HT1B receptors, which suggests that this
drug may be useful for normalizing prefrontal cognitive abilities, reducing aggression and
impulsivity, and improving cognitive function in schizophrenia.

This study will compare the effects of Eltoprazine (as an adjunctive treatment to
anti-psychotics) with Placebo in Adults with a DSM IV/DSM IV TR diagnosis of schizophrenia,
in potentially improving one or more dimensions of cognitive impairment associated with
schizophrenia.

Inclusion Criteria:

Males and Females, 18-65 years of age, who meet the DSM-IV-TR for schizophrenia.

Must test negative for pregnancy at the time of enrollment based on a pregnancy test &
agrees to use birth control during study.

Performance less than the max cutoff (in parentheses) for ONE of the following MCCB tests:
i) Letter-number span (20); ii) HVLT total (31); and iii) CPT d-prime (3.47) BPRS
Hallucinatory Behavior or Unusual Thought Content item scores ≤ 5

BPRS Conceptual Disorganization item score ≤ 4

Simpson-Angus Scale total score ≤ 6

CDRS total score ≤ 10

Able to complete the baseline MCCB validly as assessed by tester

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 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 within the last month or a
DSM-IV diagnosis of alcohol or substance dependence 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 at Visit 1,or are currently at risk of suicide in the opinion of the
Investigator.

Patients with a hx 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 PE, ECG, or lab assessments. Clinically significant
renal disease (e.g. chronic renal insufficiency with 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 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 MAOIs during the 2 weeks (14 days) prior to Baseline. Have used any SSRI, a 5HT1A
agonist or other serotonin-mediated treatment for any reason during the 4 weeks prior to
Baseline.

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.