Study of LY2140023 in Schizophrenia Comparing LY2140023, Olanzapine, and Placebo

Study Overview
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Brief Summary
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Assess the efficacy of a new drug (a receptor agonist that modulates the glutamatergic activity) in the treatment of schizophrenia. The primary objective of this study is to determine if a mGlu2/3 agonist dosed for 28 days is superior to placebo in the treatment of patients with schizophrenia as measured by the Positive and Negative Symptom Scales (PANSS) total score.

Detailed Description
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The primary objective of this study was to determine if LY2140023 dosed at 40 mg twice daily (BID) for 28 days was superior to placebo in the treatment of patients with schizophrenia as measured by the Positive and Negative Syndrome Scale (PANSS) total score. The secondary objectives of the study were to assess the safety and tolerability of LY2140023 compared with placebo and olanzapine; efficacy of LY2140023 compared with placebo in change from baseline to Visit 8 in the PANSS positive symptom subset score; efficacy of LY2140023 compared with placebo in the responder rate (defined as 25% or more decrease from baseline to Visit 8) in the PANSS total score; efficacy of LY2140023 compared with placebo in responder rate (defined as 25% or more decrease from baseline to Visit 8) in the PANSS positive symptom subset score; efficacy of LY2140023 compared with placebo in change from baseline to Visit 8 in the PANSS negative symptom subset score; efficacy of LY2140023 compared with placebo in change from baseline to Visit 8 in mood and anxiety as measured by the Hamilton Anxiety Scale (HAMA) total score; efficacy of LY2140023 compared with placebo in change from baseline to Visit 8 in the Clinical Global Impression-Severity (CGI-S); effect of LY2140023 on prolactin levels of the patients after 4 weeks of treatment; efficacy of olanzapine compared with placebo on the PANSS total score; pharmacokinetics of LY2140023 and LY404039 in patients, and to explore the relationship between exposure and efficacy.

Official Title
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A Randomized, Double-Blind Comparison of LY2140023, Olanzapine, and Placebo in the Treatment of Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: LY2140023
* Drug: olanzapine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: meet the DSM-IV criteria for schizophrenia as confirmed by modified SCID Exclusion Criteria: meet the full syndromal criteria for other Axis I disorder have taken any depot antipsychotic within 4 weeks before screening are taking mood-stabilizing agents

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: LY2140023<br>40 mg LY2140023 BID for 28 days | Drug: LY2140023<br> <br> |
| Active Comparator: Olanzapine<br>15 mg Olanzapine once daily (QD) for 28 days | Drug: olanzapine<br> <br> |
| Placebo Comparator: Placebo<br>placebo for 28 days | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine if a mGlu2/3 agonist (LY2140023) dosed for 28 days is superior to placebo in the treatment of patients with schizophrenia as measured by the Positive and Negative Symptom Scales (PANSS) total score | The primary objective of this study was to determine if LY2140023 dosed at 40 mg twice daily (BID) for 28 days was superior to placebo in the treatment of patients with schizophrenia as measured by the Positive and Negative Symptom Scale (PANSS) total score. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of LY2140023 compared with placebo and olanzapine | Safety parameters evaluated included physical and neurological examinations, vital signs, body weight, 12-lead electrocardiograms (ECGs), clinical laboratory tests, prolactin levels, and the record of symptoms. Other safety measures included the Barnes Akathisia Scale (BAS), Simpson- Angus Scale (SAS), and the Abnormal Involuntary Movement Scale (AIMS). | 28 days | 
| Efficacy of LY2140023 compared with placebo in change from baseline to Visit 8 in the PANSS positive symptom subset score | The secondary efficacy variables include the change from baseline in the PANSS positive symptoms subset score, the PANSS negative symptom subset score, CGI-S score, and HAMA total score. A patient will be included in the analysis if he or she has a baseline and at least one post-baseline measure. | 28 days | 
| Efficacy of LY2140023 compared with placebo in the responder rate in the PANSS total score | Efficacy of LY2140023 compared with placebo in the responder rate (defined as 25% or more decrease from baseline to Visit 8) in the PANSS total score | 28 days | 
| Efficacy of LY2140023 compared with placebo in responder rate in the PANSS positive and negative symptom subset score | Efficacy of LY2140023 compared with placebo in responder rate (defined as 25% or more decrease from baseline to Visit 8) in the PANSS positive and negative symptom subset score | 28 days |