A Study in Schizophrenia Patients

Study Overview
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Brief Summary
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An inpatient/outpatient study to see if LY2140023 is better than placebo in acutely ill patients with schizophrenia.

Official Title
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A Phase 2, Multicenter, Double-Blind, Placebo-Controlled Comparator Study of 2 Doses of LY2140023 Versus Placebo in Patients With DSM-IV-TR Schizophrenia

Conditions
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Schizophrenia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR; APA 2000) (Disorganized, 295.10; Catatonic, 295.20; Paranoid 295.30; or Undifferentiated, 295.90) and confirmed by the Structured Clinical Interview for DSM-IV-TR (SCID). Non pregnant female patients who agree to use acceptable birth control At entry to the study must be considered moderately ill in the opinion of the investigator Willing to participate in a minimum of 3 weeks of inpatient hospitalization and this must be appropriate for the patient in the clinical judgment of the investigator. 1 year history of Schizophrenia prior to entering the study At study entry patients with a history of antipsychotic treatment must have a lifetime history of at least one hospitalization for the treatment of schizophrenia, not including the hospitalization required for study. Patients who have never taken antipsychotic treatment may enter the study even without a history of hospitalization. At study entry patients with a history of antipsychotic treatment must have a history of at least one episode of illness exacerbation requiring an intensification of treatment intervention or care in the last 2 years, not including the present episode of illness. Patients who have never taken antipsychotic treatment may enter the study without a past history of illness exacerbation and intensification of treatment in the last 2 years. At study entry patients must have experienced an exacerbation of illness within the 2 weeks prior to entering the study, leading to an intensification of psychiatric care in the opinion of the investigator. If exacerbation occurs in patients who are presently hospitalized, the patient must not have been hospitalized longer than 60 days at entry of the study Exclusion Criteria: Participated in any clinical trial with any pharmacological treatment intervention for which they received a study-related medication in the 6 months prior to visit 1 Previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity. Treatment with clozapine at doses greater than 200 mg daily within 12 months prior to entering the study, or who have received any clozapine at all during the month before entering the study Patients currently receiving treatment (within 1 dosing interval, minimum of 4 weeks, prior entering the study) with a depot formulation of an antipsychotic medication. Patients who are currently suicidal. Females who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study. Patients with uncorrected narrow-angle glaucoma, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, uncontrolled thyroid condition or other serious or unstable illnesses Have a history of one or more seizures, except for those who experienced a single simple febrile seizure between ages 6 months and 5 years Patients are excluded if their, biological father, mother, brother, sister, or child has a history of idiopathic epilepsy. Within 1 year of study enrollment, patients have a history of central nervous system infection, uncontrolled migraine, transient ischemic attack (TIA), or head trauma with loss of consciousness or a post-concussive Patients are excluded if they have a lifetime history of any of the following: head trauma, stroke, or CNS infection with persistent neurological deficit (focal or diffuse); brain surgery; an electroencephalogram with paroxysmal (epileptiform) activity, or brain structural lesion, including developmental abnormalities, as determined by examination or previous neuroimaging studies that are consistent with a diagnosable neurological disease or syndrome. Electroconvulsive therapy (ECT) within 3 months of entering the study or who will have ECT at any time during the study. Leukopenia Medical history of Human Immunodeficiency Virus positive (HIV+) status. Higher than normal blood prolactin levels Certain electrocardiogram results

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 |
| --- | --- |
| Experimental: 160 mg LY2140023<br>80 mg LY2140023 administered orally, twice daily (BID) for up to 7 weeks. | Drug: LY2140023<br>* Administered orally.<br>|
| Active Comparator: 4 mg Risperidone<br>2 mg risperidone administered orally, BID for up to 7 weeks. | Drug: Risperidone<br>* Administered orally.<br>|
| Placebo Comparator: Placebo<br>Placebo administered orally, BID for up to 7 weeks. | Drug: Placebo<br>* Administered orally.<br>|
| Experimental: 80 mg LY2140023<br>40 mg LY2140023 administered orally, BID for up to 7 weeks. | Drug: LY2140023<br>* Administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score in overall schizophrenia population |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score in a genetic subgroup of schizophrenia patients |  | baseline, up to 7 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A change from baseline in the Personal and Social Performance (PSP) score in the overall schizophrenia population |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in the Personal and Social Performance (PSP) score in a genetic subgroup of schizophrenia patients |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in the PANSS positive scale |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in the PANSS negative scale |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in PANSS General Psychopathology subscale |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in the Clinical Global Impression-Severity Scale (CGI-S) |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in the 16-item Negative Symptoms Assessment (NSA-16) |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in the Montgomery-Ǻsberg Depression Rating Scale (MADRS) |  | baseline, up to 7 weeks of treatment | 
| PANSS total score |  | up to 7 weeks of treatment | 
| A change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score in a female patients |  | baseline, up to 7 weeks of treatment | 
| Rate of discontinuation |  | baseline, up to 7 weeks of treatment | 
| Time to discontinuation |  | baseline, up to 7 weeks of treatment | 
| A change from baseline on the EuroQol - 5 Dimensions (EQ-5D) Questionnaire |  | baseline, up to 7 weeks of treatment | 
| A change from baseline on resource utilization, as measured by the Schizophrenia Resource Use Model (S-RUM) |  | Baseline up to 7 weeks of treatment | 
| A change from baseline on functional capacity, as measured by the Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in Barnes Akathisia Scale (BAS) |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in Simpson-Angus Scale (SAS) |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in Abnormal Involuntary Movement Scale (AIMS) |  | baseline, up to 7 weeks of treatment | 
| A mean change from baseline in Prolactin levels |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in weight |  | baseline, up to 7 weeks of treatment | 
| Number of Treatment Emergent Adverse Events (TEAEs) |  | Up to 7 weeks of treatment | 
| Change from baseline in electrocardiogram parameters |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in neurological examination |  | baseline, up to 7 weeks of treatment | 
| Statistically different changes in vital signs from baseline |  | baseline, up to 7 weeks of treatment | 
| Statistically different changes in lab values from baseline |  | baseline, up to 7 weeks of treatment | 
| Population pharmacokinetics (PK) of LY2140023 |  | baseline, up to 7 weeks of treatment | 
| A change from baseline in Columbia- Suicide Severity Rating Scale (C-SSRS) |  | baseline, up to 7 weeks of treatment |