A Comparison Study of LY2140023 and Aripiprazole in Schizophrenia Patients

A Phase 3, Multicenter, Double-Blind Comparison of LY2140023 and Aripiprazole in Patients With DSM-IV-TR Schizophrenia Followed by Open-Label Treatment With LY2140023

The purpose of this study is to determine whether weight gain will be significantly less in LY2140023 than aripiprazole in patients with schizophrenia.

The primary objective of this study was to test the hypothesis that mean weight gain, as assessed by change from baseline, would be statistically significantly less for flexibly dosed LY2140023 (20, 40, or 80 mg twice daily [BID]) than for flexibly dosed aripiprazole (10, 15, or 30 mg/day) in patients with schizophrenia after 24 weeks of double-blind treatment.

This was a multicenter, randomized, double-blind, Phase 3 study to assess the safety and efficacy of LY2140023 (flexibly dosed between 20 and 80 mg BID) in patients with schizophrenia. An active control, aripiprazole (flexibly dosed between 10 and 30 mg/day), was included for comparison.

Inclusion Criteria:

• Clinical diagnosis of schizophrenia
• Female participants of childbearing age must test negative for pregnancy at screening and agree to use single, effective, medically acceptable method of birth control
• Participants must require initiation of or modification to current antipsychotic treatment as outpatients
• Participants must be considered reliable, have a level of understanding sufficient to perform all tests and examinations required by the protocol, and be willing to perform all study procedures
• Participants must be able to understand the nature of the study and have given their own informed consent

Exclusion Criteria:

• Have been on treatment with aripiprazole in the past 2 months or are aripiprazole nonresponders
• Participants who are pregnant, nursing, or intend to become pregnant within 30 days of completing the study
• Hospitalized within 2 weeks of screening or have been hospitalized for an exacerbation of symptoms of schizophrenia with a discharge date in the past 2 months
• Participants who are actively suicidal
• Participants with uncorrected narrow-angle glaucoma, history of or current seizure disorder, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, uncontrolled thyroid condition or other serious or unstable illnesses
• Participants who have had electroconvulsive therapy (ECT) within 3 months prior to screening or will have ECT at any time during the study
• Participants with known medical history of Human Immunodeficiency Virus positive (HIV+) status
• Test positive for (1) Hepatitis C virus antibody or (2) Hepatitis B surface antigen (HBsAg) with or without positive Hepatitis B core total antibody
• Participants with a corrected QT interval (Bazett's; QTcB)>450 milliseconds (msec) (male) or >470 msec (female) at screening
• Participants who have a history of inadequate clinical response to antipsychotic treatment for schizophrenia
• Participants who have received treatment with any depot formulation of an antipsychotic medication within 1 dosing interval, minimum of 4 weeks, prior to screening
• Are currently enrolled in, or discontinued within the last 60 days from, a clinical trial involving an investigational product or unapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have any other psychiatric diagnoses in addition to schizophrenia
• Have previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity
• Participants who have received an adequate treatment trial, in the opinion of the investigator, with clozapine at doses greater than 200 milligrams (mg) daily within 12 months prior to screening, or who have received any clozapine at all during the month before screening
• Diagnosis of substance-induced psychosis within 7 days of screening (or at any time during the study)