A Physical Dependence Study in Schizophrenia

A Phase 3, Short-Term, Multicenter, Placebo-Controlled, Randomized Withdrawal Study of LY2140023 Monohydrate in Patients With DSM-IV-TR Schizophrenia

The purpose of this study is to determine whether or not people with schizophrenia who take LY2140023 become physically dependent on it, and experience a series of symptoms such as craving to have the drug when they stop using it.

This trial consists of two phases: An open-label phase consisting of up to 4 weeks and a double-blind phase consisting of up to 3 weeks.

This was a short-term, multicenter, placebo-controlled, randomized withdrawal study comparing LY2140023 with placebo in the treatment of outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR [APA 2000]) schizophrenia. Patients were male or female outpatients, 18 to 65 years of age (inclusive) at study entry, with a diagnosis of schizophrenia as defined in the DSM-IV-TR

The primary objective of this study was to assess whether LY2140023, when administered in an acute-treatment trial with flexible doses (40 mg or 80 mg) BID, was associated with physical dependence, as measured by the occurrence of withdrawal symptoms during a randomized withdrawal phase in patients diagnosed with schizophrenia. Assessment was to be based on a comparison of randomized LY2140023-treated patients with those on placebo, as measured by the maximum of the 3-day moving average of the patient's total score on the Discontinuation Symptom Checklist-Modified Rickels (DSCMR).

Inclusion Criteria:

• Clinical diagnosis of schizophrenia
• Female participants of childbearing potential must test negative for pregnancy at study entry and agree to use a single, effective, medically acceptable method of birth control
• Participants must require a modification of antipsychotic medication or the initiation of antipsychotic medication, as indicated by their present clinical psychiatric status and/or treatment tolerability as outpatients
• Participants must be considered reliable and have a level of understanding sufficient to perform all tests and examinations required, 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 a Clinical Global Impression-Severity Scale (CGI-S) score >4 at study entry
• Have any other psychiatric diagnoses in addition to schizophrenia
• Participants who have a history of inadequate clinical response to antipsychotic treatment for schizophrenia
• Participants who have received an adequate treatment trial, in the opinion of the investigator, with clozapine at doses >200 mg daily within 12 months prior to study entry, or who have received any clozapine at all during the month before study entry
• Participants who are actively suicidal
• Female participants who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study
• Have known, uncorrected, narrow-angle glaucoma
• Participants who have had electroconvulsive therapy (ECT) within 3 months of study entry or who will have ECT at any time during the study
• Participants with known medical history of human immunodeficiency virus positive (HIV+) status
• Participants who test positive for Hepatitis C virus antibody or Hepatitis B surface antigen (HBsAg) with or without positive Hepatitis B core total antibody
• Participants with current or a history of seizure disorder, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, uncontrolled thyroid condition or other serious or unstable illnesses
• Participants with a corrected QT interval (Bazett's; QTcB) >450 milliseconds (msec) (male) or >470 msec (female) at study entry (based on the central vendor's electrocardiogram [ECG] overread)
• Have previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity
• Are currently enrolled in, or discontinued within the last 60 days from, a clinical trial involving an investigational product for 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