A Long-Term, Open-Label, Study on Schizophrenia

Study Overview
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Brief Summary
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The primary purpose of the study is to help answer the following research questions: How LY 2140023 can be tolerated by patients with Schizophrenia compared to standard of care treatment in 52 weeks time period. Whether LY 2140023 can help patients with Schizophrenia.

Detailed Description
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The study includes 2 treatment periods. Study Period I will begin at patient randomization (enrollment into Study HBBO) and continue through the first 2 years of treatment. Study Period II will be only for patients randomized to treatment with LY2140023, and will begin after the patient has completed the second year of treatment. Patients who qualify for enrollment will be randomized in a 3:1 ratio (LY2140023 versus standard of care, respectively) into 2 treatment groups: flexible, twice-daily dose of LY2140023 or standard-of-care (olanzapine, risperidone, aripiprazole, or quetiapine). Those assigned to LY2140023 will have the option to continue on LY2140023 after 2 years if deemed appropriate by the investigator.

Official Title
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A Long-Term, Open-Label, Multicenter Study of LY2140023 Compared to Atypical Antipsychotic Standard of Care in Patients With DSM-IV-TR Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: LY2140023
* Drug: Olanzapine
* Drug: Aripiprazole
* Drug: Risperidone
* Drug: Quetiapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have met all entry criteria for, and have completed, an acute, placebo-controlled clinical trial of LY2140023 (such as Study H8Y-MC-HBBM, or other acute, placebo-controlled LY2140023 studies if allowed by the protocols for those studies). Female patients of childbearing potential must agree to use a single, effective, medically acceptable method of birth control. Patients must be considered reliable and have a level of understanding sufficient to perform all tests and examinations required by the protocol. Patients must be able to understand the nature of the study and have given their own informed consent. Exclusion Criteria: Are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving an investigational product or nonapproved use of a drug or device (other than LY2140023), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Patients for whom treatment with olanzapine, risperidone, aripiprazole, quetiapine, or LY2140023, as specified in this protocol, is relatively or absolutely clinically contraindicated. Patients who have received treatment with clozapine at doses greater than 200 mg daily within 12 months prior to study enrollment, or who have received any clozapine at all during the month before study enrollment. Patients who require concomitant treatment with any other medication with primary central nervous system activity, other than those allowed in study protocol. Patients have risk of suicide. Patients diagnosed with substance dependence or substance abuse within the 6 months prior to study enrollment. Patients diagnosed with substance-induced psychosis within 7 days of study enrollment or at any time during the study. Female patients who are pregnant, nursing, lactating or who intend to become pregnant within 30 days of completing the study. Have known glaucoma. Have a history of some types of seizures. Have seizure liability inconsistent with the exclusion criteria of the completed acute feeder study. Patients who have had electroconvulsive therapy (ECT) within 3 months of study enrollment or who will have ECT at any time during the study. Patients with known Human Immunodeficiency Virus positive (HIV+) status. Patients have a serious disease, such as recent stroke, heart, liver, kidney, lung or blood diseases Patients with Parkinson's disease Are incapable of participating in the study or are unwilling to engage in a meaningful way as study participants.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br> | Drug: Olanzapine<br>* Tablets or capsules, given orally, consistent with approved labeling and local practice for 104 weeks<br>* Other names: LY170053;Drug: Aripiprazole<br>* Tablets or capsules, given orally, consistent with approved labeling and local practice for 104 weeks<br>Drug: Risperidone<br>* Tablets or capsules, given orally, consistent with approved labeling and local practice for 104 weeks<br>Drug: Quetiapine<br>* Tablets or capsules, given orally, consistent with approved labeling and local practice for 104 weeks<br>|
| Experimental: LY2140023<br>20mg, 40mg or 80mg After 104 weeks, patients have the option to continue on treatment until the end of the study | Drug: LY2140023<br>* Administered orally, twice daily for 104 weeks<br>* Other names: mGlu 2/3 Prodrug II;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to discontinuation due to adverse events |  | Baseline through 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to 52 weeks endpoint in PANSS (Positive and Negative Syndrome Scale) |  | Baseline, 52 weeks | 
| Change from baseline to 52 week endpoint in Clinical Global Impression-Severity (CGI-S) |  | Baseline, 52 weeks | 
| Change from baseline to 52 week endpoint in NSA-16 (16-item Negative Symptoms Assessment) |  | Baseline, 52 weeks | 
| The number of patients with statistically significant changes (treatment emergent ideation and behavior; improvement) based on the Columbia Suicide Severity Rating Scale (C-SSRS) |  | 52 weeks, 104 weeks, end of study | 
| Change from baseline to 52 week endpoint in PSP scale (Personal and Social Performance) |  | Baseline, 52 weeks | 
| Change from baseline to 52 week endpoint in the SWN Scale (Subjective Well-Being Under Neuroleptic Treatment) |  | Baseline, 52 weeks | 
| Change from baseline to 104 week endpoint in the Schizophrenia Resource Use Model (S-RUM) |  | Baseline, 104 weeks | 
| Change from baseline to 104 week endpoint in the EuroQoL Questionnaire-5 Dimension (EQ-5D) |  | Baseline, 104 weeks | 
| Change from 52 week to 104 week endpoint in PANSS (Positive and Negative Syndrome Scale) |  | 52 weeks, 104 weeks | 
| Change from 52 week to 104 week endpoint in Clinical Global Impression-Severity (CGI-S) |  | 52 weeks, 104 weeks | 
| Change from 52 week to 104 week endpoint in NSA-16 (16-item Negative Symptoms Assessment) |  | 52 weeks, 104 weeks | 
| Change from 104 week to study endpoint in Clinical Global Impression-Severity (CGI-S) |  | 104 weeks, end of study | 
| Change from baseline to 104 week endpoint in PSP scale (Personal and Social Performance) |  | Baseline, 104 weeks | 
| Change from baseline to 104 week endpoint in the SWN Scale (Subjective Well-Being Under Neuroleptic Treatment) |  | Baseline, 104 weeks | 
| Change from Baseline to 52 week endpoint in the Schizophrenia Resource Use Model (S-RUM) |  | Baseline, 52 weeks | 
| Change from 104 week to study endpoint in the EuroQoL Questionnaire-5 Dimension (EQ-5D) |  | 104 weeks, end of study | 
| Change from baseline to 52 weeks endpoint in PANSS (Positive and Negative Syndrome Scale) in a genetically defined subgroup |  | Baseline, 52 Weeks |