A Study for Patients With Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that 1 or more dose levels of LY2140023 given orally to patients with schizophrenia twice daily for 4 weeks will have significantly greater effect than placebo.

Official Title
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A Multi-Center, Inpatient, Phase 2, Double-blind, Placebo-Controlled Dose Ranging Study of LY2140023 in Patients With DSM-IV Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: LY2140023
* Drug: LY2140023
* Drug: LY2140023
* Drug: LY2140023
* Drug: Olanzapine
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Some Inclusion Criteria: Patients must have a diagnosis of Schizophrenia as defined in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (Disorganized, 295.10; Catatonic, 295.20; Paranoid, 295.30; Residual, 295.60; or Undifferentiated, 295.90) and confirmed by the Structured Clinical Interview for DSM-IV (SCID). Patients must meet the following psychopathologic severity criteria at Visit 1: Brief Psychiatric Rating Scale (BPRS) total score, extracted from the Positive and Negative Syndrome Scale (PANSS), of at least 45 (18-item version, in which 1 indicates absent and 7 indicates severe). In addition, item scores of at least 4 (moderate) will be required on 2 of the following BPRS items: conceptual disorganization, suspiciousness, hallucinatory behavior, and/or unusual thought content. Patients must receive a rating of 4 (moderately ill) or greater on the Clinical Global Impression-Severity (CGI-S) scale at Visit 1. Patients in whom, in the opinion of the investigator, a switch to another antipsychotic medication or initiation of an antipsychotic medication is acutely indicated. Some Exclusion Criteria: Patients in whom treatment with olanzapine or placebo is relatively or absolutely clinically contraindicated. Patients who have a history of inadequate response to an adequate treatment trial with olanzapine, in the opinion of the investigator. Patients who have received treatment with olanzapine within 6 weeks prior to Visit 1. Patients who have received treatment with clozapine at doses greater than 200 mg daily within 12 months prior to Visit 1, or who have received any clozapine at all during the month before Visit 1. Patients who have a history of an inadequate response, in the opinion of the investigator, to 2 or more adequate antipsychotic medication trials of at least 8 weeks duration in the past 12 months prior to Visit 1. Patients with acute, serious, or unstable medical conditions, including (but not limited to) inadequately controlled diabetes (hemoglobin A1c (HbA1c) 8%), severe hypertriglyceridemia (fasting triglycerides 5.6 mmol/L, recent cerebrovascular accidents, serious acute systemic infection or immunologic disease, unstable cardiovascular disorders (including ischemic heart disease), malnutrition, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, or hematologic diseases.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>160mg of LY2140023, taken orally as 80mg twice daily, for up to 4 weeks. | Drug: LY2140023<br>* 80mg, PO (by mouth) BID (twice a day) for up to 4 weeks.<br>|
| Experimental: 2<br>80mg of LY2140023, taken orally as 40mg twice daily, for up to 4 weeks. | Drug: LY2140023<br>* 40mg, PO (by mouth) BID (twice daily) for up to 4 weeks.<br>|
| Experimental: 3<br>40mg of LY2140023, taken orally as 20mg twice daily, for up to 4 weeks. | Drug: LY2140023<br>* 20mg, PO (by mouth) BID (twice daily) for up to 4 weeks.<br>|
| Experimental: 4<br>10mg of LY2140023, taken orally as 5mg twice daily, for up to 4 weeks. | Drug: LY2140023<br>* 5mg, PO (by mouth) BID (twice daily) for up to 4 weeks.<br>|
| Placebo Comparator: 5<br>Placebo of LY2140023, taken orally twice daily, for up to 4 weeks. | Drug: Placebo<br>* Taken PO (by mouth) BID (twice daily) for up to 4 weeks.<br>|
| Active Comparator: 6<br>Placebo, taken orally every morning, followed by Olanzapine 15mg taken orally every evening for up to 4 weeks. | Drug: Olanzapine<br>* 10mg, PO (by mouth) QPM (every evening) for the first 3 days, then 15mg PO QPM, for up to 4 weeks.<br>Drug: Placebo<br>* Taken PO (by mouth) QAM (every morning) for up to 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale (PANSS) total score |  | over 4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PANSS subscores: positive subscore; negative subscore; general psychopathology subscore and cognitive subscore |  | over 4 weeks of treatment | 
| Clinical Global Impression-Severity (CGI-S) |  | over 4 weeks of treatment | 
| Drug Attitude Inventory-10 (DAI-10) |  | over 4 weeks of treatment | 
| Response and Remission Rates |  | over 4 weeks of treatment | 
| Assessment of Cognition in Schizophrenia (BACS) Symbol Coding Task |  | over 4 weeks of treatment | 
| Montgomery-Asberg Depression RatingScale (MADRS) |  | over 4 weeks of treatment | 
| Safety and Tolerability |  | over 4 weeks of treatment | 
| Pharmacokinetics |  | over 4 weeks of treatment |