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

Study Overview
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Brief Summary
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The purpose of this study is to determine if eltoprazine (as an adjunct to anti-psychotic medication) improves one or more aspects of cognitive impairment in adult schizophrenic patients.

Detailed Description
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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.

Official Title
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Randomized, Double-blind, Parallel Trial Comparing the Effects of Eltoprazine (Adjunct to Anti-psychotics) With Placebo in Adults With Schizophrenia, in Improving One or More Dimensions of Cognitive Impairment Associated With Schizophrenia

Conditions
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Cognitive Impairment, Schizophrenia

Intervention / Treatment
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* Drug: Eltoprazine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eltoprazine<br>eltoprazine pill 2.5mg bid, eltoprazine pill 5mg bid, eltoprazine 7.5mg bid | Drug: Eltoprazine<br>* Comparison of eltoprazine, dosed orally, for 8 weeks<br>* Other names: eltropazine hydrochloride;|
| Placebo Comparator: Placebo<br>placebo pill 2.5mg bid, placebo pill 5mg bid, placebo 7.5mg bid | Drug: Placebo<br>* Placebo to match eltoprazine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MATRICS Consensus Cognitive Battery (MCCB) | Assessment of cognitive effects over time measured suing the MCCB battery | At Baseline and every 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous Performance Test-AX Version (CPT-AX) | Assessment of Cognitive effects over time measured using the Continuous Performance Test (AX version) | At Baseline and every 4 weeks | 
| N-Back | Assessment of Cognitive effects over time measured using the N-Back Working Memory Test | At Baseline and every 4 weeks | 
| Brief Psychiatric Rating Scale (BPRS) |  | At Baseline and every 2 weeks | 
| Calgary Depression Scale (CDS) |  | At Baseline and every 2 weeks | 
| Scale for Assessment of Negative Symptoms (SANS) |  | At Baseline and every 2 weeks | 
| Simpson-Angus Extrapyramidal Symptom Rating Scale (SAS) |  | At Baseline and every 2 weeks | 
| Abnormal Involuntary Movement Scale (AIMS) |  | At Baseline and every 2 weeks | 
| Barnes Akathisia Scale (BAS) |  | At Baseline and every 2 weeks | 
| Columbia Suicide Severity Rating Scale (C-SSRS) |  | At baseline and end of study; every two weeks if there is a change in the CDRS suicidality rating to a score of 2 or 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CIAS, Cognition, Schizophrenia, Eltoprazine