A Study to Determine the Safety, Tolerability and Efficacy NW-3509A in Patients With Chronic Schizophrenia

Study Overview
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Brief Summary
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A 4-week Phase IIa study to evaluate the safety and tolerability and efficacy of NW-3509A in patients with chronic schizophrenia that are not responding adequately to their current antipsychotic medication (aripiprazole or risperidone). NW-3509A is given as an oral dose range of 15 to 25 mg, BID in a 1:1 ratio.

Detailed Description
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This is a prospective, 4-week, randomized, double-blind, placebo-controlled, study designed to evaluate the safety, tolerability, and preliminary efficacy of an oral dose range of NW-3509A of 30 to 50 mg/day (15 to 25 mg, BID) in patients with chronic schizophrenia on a stable dose of an antipsychotic (aripiprazole or risperidone). A minimum of 90 patients will be randomized in a 1:1 ratio to receive either NW-3509A (n=45) or placebo (n=45). Dose increases will be performed only during in-patient setting. Safety and efficacy assessments will be done on a weekly basis during the randomized treatment period. The assessment of safety will be based on laboratory tests (biochemistry, hematology, and urinalysis), 12-lead standard ECG, vital signs, physical examinations, neurological examinations, C-SSRS, ESRS-A, subjective reporting of any AE by the subject, objective observation of any AE by the Investigator. Pharmacokinetic samples will be taken at various time-points. Efficacy assessments will include the PANSS, CGI-C, CGI-S and the Strauss-Carpenter Level of Functioning (LOF) scale.

Official Title
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A Phase IIA, Prospective, Randomized, Double-blind, Multiple-dose Study of NW-3509A in Chronic Schizoprhenia Patients Not Responding to Their Current Anti-psychotic Medication

Conditions
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Chronic Schizophrenia

Intervention / Treatment
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* Drug: NW-3509A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/female; if female, must not of childbearing potential 18 to 65 years of age, inclusive; Has a current diagnosis of schizophrenia Has a total score on the PANSS < 75. Positive symptoms sub-scale score not to exceed 15; score of ≥4 on no more than 2 positive symptoms Has a Clinical Global Impression - Severity of disease (CGI-S) rating of mildly to moderately severely ill. Is in need of anti-psychotic treatment and is currently receiving a stable dose (minimally for 4 weeks prior to screening of oral risperidone or aripiprazole (at least 2 mg risperidone dose-equivalent). Current symptoms present for at least one month. Patient agrees to be hospitalized for up to 2 days at the start of dosing and at each dose increase

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NW-3509A<br>Patients will start on NW-3509A 15 mg BID and be up-titrated to 20mg, and 25mg BID dependent on tolerability. | Drug: NW-3509A<br>* Patients will be given oral doses of 15, 20 and 25 mg BID of NW-3509A<br>|
| Placebo Comparator: Placebo<br>Patients will receive matching placebo BID | Drug: Placebo<br>* Patients will be given oral dose of matching Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of NW-3509A in patients with schizophrenia on a stable dose of their current antipsychotic medication (aripiprazole or risperidone). | To evaluate the safety and tolerability of NW-3509A given as an oral dose range of 30 to 50 mg/day (15 to 25 mg, BID) in patients with schizophrenia on a stable dose of their current antipsychotic medication (aripiprazole or risperidone). | 27 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Positive and Negative Syndrome Scale (PANSS) | Assessment of the PANSS - a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control, will be carried out at every visit | 27 days | 
| Assessment of CGI-S (severity) and CGI-C (change) | Measure of change from baseline will be done at every assessment | 27 days; change from baseline | 
| Assessment of Strauss-Carpenter Level of Functioning (LOF) scale | The LOF scale will be used at baseline and end of study, to evaluate the clinical outcome | 27 days; baseline and end of study | 
| Measurement of plasma concentration Cmax | Blood samples will be collected for PK evaluation at time points | 27 days |